Breaking Physiological Barriers in Women's Health: Mucoadhesive and Stimuli-Responsive Nanomaterials

Maddox Parsons: writing – original draft, writing – review and editing. Alivia R. Parker: writing – original draft, writing – review and editing. Luke Schneider: writing – original draft, writing – review and editing. Trisha Sullivan: writing – original draft, writing – review and editing. Brittany E. Givens: conceptualization, funding acquisition, writing – original draft, writing – review and editing, supervision.

This publication was made possible by Grant Number K12DA035150 from the Office of Women's Health Research and the National Institute on Drug Abuse at the National Institutes of Health (NIH) and Grant Number R03EB037115 from the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH.

Biomaterials address critical, unmet needs in engineering and medicine. Tissue engineering, organoid engineering, micro‐physiological system design, and drug delivery system design are all applications of biomaterials in engineering that can advance science, technology, engineering, and medicine (STEM) research (Koons  2025 ; Oyen  2022 ). Women's health encompasses age‐related changes, hormonal fluctuations, and the distinct impacts of diseases and conditions, given female physiology (Moore and Raghavan  2025 ). In this review, recent advances in the areas of mucodiffusive drug delivery vehicles and stimuli‐responsive drug delivery vehicles are highlighted for the unique barriers experienced with the female reproductive system. Throughout this review article, the term “women's health” is used to describe individuals with female reproductive organs and female breasts. However, the authors acknowledge that sex and gender are not identical definitions, nor are they all‐encompassing. Therefore, individuals who may be affected by these conditions and those who may benefit from these solutions may span a broader range of identities. Traditionally, conditions that disproportionately affect women and investigations that highlight anatomical and physiological differences for women compared with men have been understudied. Part of this failure of progress in the field of specifically women's health can be attributed to the disproportionate underfunding of it compared to men's specific health condition research (Mirin  2021 ). This underscores the need for innovative therapeutic technologies to address longstanding gaps in clinical care. Despite significant advances in modern medicine, women's health continues to face persistent therapeutic gaps in which current, widely used drug delivery strategies fail to provide safe, effective, and localized treatment. Engineering tools have expanded the research landscape for addressing these knowledge gaps (Oyen  2023 ). The female reproductive system consists of the vagina, cervix, uterus, fallopian tubes, and ovaries (Figure  1 ). Drug delivery to the female reproductive system is challenging due to the unique physiology and barrier protection offered through the vagina and cervix. The uterine body is comprised of three tissue layers: the endometrium, myometrium, and perimetrium, with the endometrium serving as the primary tissue layer for abnormalities (Esmaeilzadeh and Nasirzadeh  2023 ). However, the vaginal walls are also highly vascularized and therefore are a favorable site for localized drug delivery (Alexander et al.  2004 ). Specifically, vaginal drug delivery is common for antifungals, contraceptives, and other hormonal therapies. Most uterine abnormalities form within the endometrial layer of the uterus. Other gynecological malignancies include cervical cancer, ovarian cancer, and vulvovaginal cancer (Berezowitz and Givens  2025 ). Diseases and conditions influencing these organs include, but are not limited to, uterine fibroids, endometriosis, prolapse, vaginal stenosis, bacterial, viral, and fungal infections. Biomaterial systems offer solutions to these through structural support, localized drug delivery, and other scientific innovations. Diagram of the human female reproductive organs, including the vagina, cervix, uterus, fallopian tubes, and ovaries. Additionally, it includes the uterine tissue layers. BioRender. Several prevalent women's health needs, such as gynecological cancers, endometriosis, vaginal infections, contraceptive delivery, and fertility enhancement have all shown potential for being addressed via nano‐scale drug delivery platforms (Cai et al.  2022 ; Swingle et al.  2023 ). Existing drug delivery methods for treating women's health needs include oral hormonal therapies, suppositories and creams via vaginal delivery, intravaginal rings, and implants/systemic therapies (das Neves et al.  2021 ; Mehta et al.  2021 ; Swingle et al.  2023 ). These methods are insufficient for several reasons, but the most consistent is that they are not well‐suited to the physiological environment that the system is intended to remedy. For example, the mechanical properties of the multi‐layered uterine tissue change as a function of the menstrual cycle and pregnancy (Fodera et al.  2024 ). Like the uterus, vaginal tissue is comprised of multiple layers, and these layers undergo mechanical variation (Hicks et al.  2024 ). Additionally, the vaginal tissue has high cervicovaginal mucosal turnover, acidic pH, hormone fluctuations, and microbiome changes (das Neves et al.  2021 ). Therefore, existing therapies tend to have lower efficacy. In this review article, we detail the most promising applications of these biomaterials‐based nanoparticles in women's health and outline potential future directions for research. The vaginal and cervical mucosa serve as selective barriers, with the epithelium, underlying connective tissue, and mucus/cervical fluid layers restricting drug permeation and promoting rapid dispersion of drug doses (Acarturk  2009 ). The vagina is an elastic, fibromuscular organ that has a critical role in menstruation, pregnancy, and sexual health (Balakrishnan et al.  2022 ; Mazloomdoost et al.  2017 ). The vaginal mucosa plays an important role in immunity and pathogen defense, because the vagina serves as a connection between the cervix and the external environment (Kumamoto and Iwasaki  2012 ). The dense mucus network, tight‐junction epithelium, immune cell clearance, and competitive microbiome interactions must all be overcome when considering the effectiveness of a drug delivery platform to traverse the mucus and reach the epithelial tissue. For example, the mucosal network has been shown to trap foreign particles and limit the diffusion of drug vehicles toward the epithelium (Zierden et al.  2021 ). Additionally, the biochemical environment is constantly changing. A healthy vaginal pH is typically 3.5–4.5, but it can shift to neutral or even alkaline under certain conditions (Lykke et al.  2021 ). These changes in pH, along with changes in the microbiome, can alter the ionization, stability, and absorption of drugs within the female reproductive system. Finally, XX females of reproductive age follow a 28‐day hormonal cycle that influences the levels of estrogen, progesterone, testosterone, luteinizing hormone, and follicle‐stimulating hormone (FSH). These hormonal shifts result in cyclic alterations of thickness, vascularity, mucus composition, and mechanical stresses (Sanchez Armengol et al.  2025 ). Together, these complex factors imply that standard drug delivery systems struggle to maintain adequate drug concentration, retention, and release over desired durations. Biocompatibility has several definitions and universally describes the ability of a biomaterial to be implanted into the body without adverse local or systemic effects (Ratner  2011 ). Additionally, biocompatibility is a function of interactions between the tissue and the material (Anderson and Miller  1984 ). Considering these two definitions as a basis, the biocompatibility of materials for women's health applications must exist within the tissue of interest, for example, the female reproductive tract, without eliciting adverse effects. Biomaterials may be derived from natural sources, which are biomaterials derived from plants, animals, and microorganisms (Asadi et al.  2024 ). These natural biomaterials often possess functional moieties, such as —NH 2 , —COOH, and —OH, which make them responsive to native physiological stimuli (Samiraninezhad et al.  2023 ). In contrast, synthetic biomaterials are derived from polymers synthesized in the laboratory, such as polyurethanes, polyesters, polymethacrylates, and others. Material selection, then, depends on both the desired applications and the delivery site. For example, nanogels have high biocompatibility, local retention, and tuneable therapeutic release, including in the female reproductive tissues (Huynh et al.  2023 ; Yang et al.  2022 ). Nanogel‐based platforms are highly deformable and therefore adapt to tissue geometry and swelling behavior, which enables conformational contact. Furthermore, these nanogels have tuneable crosslink density and can incorporate functional groups that enable responsive behavior to local stimuli (Dos Santos et al.  2020 ). These nanogels have been increasingly referenced in reviews of vaginal and mucosal delivery systems to overcome mucosal clearance and variable physiological conditions (Dos Santos et al.  2020 ). Building on this clinical rationale, the remainder of this review highlights how emerging nanogel systems are being engineered to address these challenges across several application areas in women's health. In this review, we first introduce key materials‐design strategies for passive and active targeted cancer therapies. Passive targeting leverages the physicochemical properties of nanogels and tumor microenvironment features such as the enhanced permeability and retention (EPR) effect in cancer, whereas active targeting involves ligand‐receptor interactions that direct nanogels to specific cell‐associated markers. For example, gynaecologic cancers such as ovarian, cervical, and endometrial cancers typically overexpress CD44, a cell‐surface glycoprotein that can be selectively engaged using hyaluronic acid‐based nanogels. Additionally, CD44 is also natively expressed in the uterus, with expression varying as a function of the menstrual cycle (Yaegashi et al.  1995 ). We then examine nanogel design strategies aimed at improving drug transport across mucosal tissues through the foundational concepts of mucoadhesion and mucodiffusion. Mucoadhesive formulations are engineered to interact with and transiently bind to components of the vaginal mucus layer, which prolongs residence time and enhances local drug availability. In contrast, mucodiffusive systems are designed to minimize adhesive interactions and instead traverse the mucus network to reach the underlying epithelium more effectively. These two approaches represent distinct yet complementary strategies for overcoming the significant barrier functions of the female reproductive mucosa, and their selection is governed by the therapeutic objective and required depth of tissue access. Finally, we review the rapidly growing field of stimuli‐responsive (or “smart”) nanogels. Targeted responsive versions of these smart nanogels incorporate molecular cues or binding motifs that concentrate responsiveness within defined tissues or receptor‐expressing cell subsets. In contrast, non‐targeted responsive systems respond to general environmental triggers, such as temperature or pH, without their action being directed by specific cell populations. Two key classes of smart nanogels are highlighted in this article: thermo‐responsive, which undergo phase transitions or swelling changes in response to physiologically relevant temperature changes, and pH‐responsive, which use pH gradients present throughout the female reproductive tract to modulate drug release. These adaptive platforms exemplify how smart materials can be engineered to align release kinetics and activity with dynamic physiological conditions.

An integral aspect of the female reproductive tract is cervicovaginal mucus (CVM). CVM mimics the nasal mucosa in that the nasal mucosa is tailored for inhalable contaminants (Beule  2011 ), however, the CVM serves as a protective barrier for the vagina and internal female reproductive organs and is a selective barrier for foreign particulates and pathogens. Secreted primarily by the endocervical epithelium, the CVM is comprised mainly of water and glycoproteins (Lacroix et al.  2020 ), serves as a selective barrier, and provides immune defense (Acarturk  2009 ; Anahtar et al.  2018 ; Kumamoto and Iwasaki  2012 ; Lacroix et al.  2020 ). Since CVM is present in epithelial tissues and contacts the external environment, it serves as a defensive mechanism between the two. CVM also influences fertility by changing its viscosity throughout the menstrual cycle to promote or inhibit sperm transport (Anahtar et al.  2018 ; Lacroix et al.  2020 ). Engineered biomaterials can take advantage of CVM properties (Ensign et al.  2012 ; Hernández‐González et al.  2023 ) by leveraging mucoadhesion and mucodiffusion in therapeutic delivery technologies. Biological adhesion refers to the attachment of natural or synthetic materials to a biological surface via hydrophobic interactions, hydrogen bonding, or physical interlocking (Morales and McConville  2011 ; Pollini et al.  2025 ). Cell adhesion is mediated by cadherins, integrins, selectins, and proteoglycans, and changes in the expression of these molecules can provide insights into cell adhesion, including those occurring during cancer cell progression and metastasis (Mehanna et al.  2025 ). Additionally, adhesion properties differ by cell type, even when cells are colocalized within the same tissue, as evidenced by differences in gravitational resistance between mature cervical cells and placental trophoblasts (Bailey‐Hytholt et al.  2021 ). Mucoadhesion specifically describes the attractive forces that occur between a material, such as a nanoparticle, and components of mucus such as glycoproteins and sialic acids (Thornton and Sheehan  2004 ). This phenomenon can be utilized within drug delivery to facilitate controlled release. In contrast, mucodiffusion is a process by which a particle or substance moves through a mucus layer, similar to the diffusion theory of mucoadhesion (Shaikh et al.  2011 ). Since cervicovaginal mucus acts as a protective barrier against unwanted substances, it can be difficult to deliver a drug through this barrier. The CVM is predominantly comprised of water and gel forming mucins, and its barrier properties are strengthened by the high viscoelasticity of the CVM (Adnane et al.  2018 ; Lai et al.  2009 ). Throughout the menstrual cycle, the CVM is dynamic with different levels of immunoactive proteins, including immunoglobulin A, lactoferrin, and lysozyme as well as inflammatory biomarkers, such as interleukin (IL)‐1β, IL‐6, and IL‐8 (Adnane et al.  2018 ). The penetrative ability of CVM varies as a function of the menstrual cycle and during pregnancy (Chrétien  2003 ). Although sparse, the existing literature agrees that mucus glycoproteins dominate the mucoadhesive properties of the CVM (Figure  3 ). Mucodiffusive polymers also offer a means to overcome the rapid mucosal turnover of the CVM, estimated at less than a few hours (Chater et al.  2018 ), which undermines the effectiveness of mucoadhesive technologies. Differences between mucodiffusion and mucoadhesion of nanomaterials. Mucodiffusion refers to the penetration of particles through the mucus layer whereas mucoadhesion refers to the attachment of particles to components of the mucus, such as glycoproteins. BioRender. Mucoadhesive polymers have been identified as having favorable properties for attaching to mucus components. For example, the presence of hydroxyl, carboxyl, or amine functional groups can form hydrogen bonds with the mucus layer. Also, the polymer chains need to be flexible and possess charged surfaces. The polymeric chain of mucoadhesive polymers should also remain structurally intact throughout. Examples of mucoadhesive polymers include thiolated polymers, such as chitosan‐iminothiolane and poly(methacrylic acid)‐cysteine, which contain a free thiol group in the polymer backbone (Kavitha et al.  2011 ). Additionally, thiolated polymers may be cleaved via enzymes (Lee et al.  2013 ). Chitosan is a natural polymer with strong mucoadhesive qualities owing to its positive charge and electrostatic interactions with CVM (Andersen et al.  2015 ). The use of mucoadhesive polymers in drug delivery increases retention time on the mucus surface, therefore increasing the capacity of the polymeric system for controlled release (Bruschi et al.  2020 ). Several theories explain the mechanism of mucoadhesion, including the wetting, electrostatic, diffusion, and adsorption theories (Shaikh et al.  2011 ). Each theory describes distinct phenomena in the interactions between mucus and other materials. For example, the wetting theory applies to liquid systems with viscosities near that of water (1 mPa·s). Therefore, wetting theory describes adhesion caused by surface tension at the mucus surface. Additionally, the ability of the adhesive agent to interact with the ridges of a surface is highlighted within this theory. In contrast, the electrostatic theory focuses on charge transfer between the adhesive agent and the mucus surface. In the female reproductive system, the CVM is negatively charged; therefore, positively charged materials are attracted to it according to this theory. Similarly, the adsorption theory describes adhesion based on intermolecular interaction such as hydrogen bonding. Hydrogen binding of a polymer backbone may contribute to mucoadhesion in the CVM (Wake  1978 ). Finally, the diffusion theory assumes that polymer chains interacting with the mucus surface penetrate the top layer and diffuse within the mucus. Certain characteristics of the polymers make them well‐suited to penetrate the mucus barrier. A polymer with an overall neutral charge limits its interactions with the mucus, which promotes penetration. Hydrophilic polymers also influence the degree of penetration by limiting hydrophobic interactions between the polymer and mucus (Bruschi et al.  2020 ). Examples of mucodiffusive polymers include zwitterionic polyethylene glycol (PEG)‐functionalized polymers that result in a hydrophilic molecule with a zero net charge (Tang et al.  2009 ). PEG is known to have mucodiffusive properties; particles coated with PEG can diffuse uniformly through mucus layers (Valamla et al.  2022 ). Although there is limited information on PEG use in gels for diffusion, the qualities of PEG used in particle diffusion could be capitalized on in gels as well. Overall, less work has focused on mucodiffusive drug delivery than on mucoadhesive drug delivery. This can be attributed to the challenges faced when navigating movement through such an advanced barrier such as the CVM rather than adhesion to it. However, much of the research on mucoadhesion can be used to better understand mucodiffusion as many of the polymeric attributes improving one strategy can limit the other. Over the course of the menstrual cycle, the body undergoes physiological changes that affect the properties of the CVM secreted. These changes can affect factors including viscosity, pH, and even the CVM's overall composition (Chappell et al.  2014 ). Variations in these qualities of the CVM then affect a formulation's ability to achieve optimal mucoadhesion or mucodiffusion. Early in the menstrual cycle and during menstruation, the CVM is typically watery due to increased oestradiol (Adnane et al.  2018 ; Chappell et al.  2014 ). This has the potential to increase mucodiffusion and decrease mucoadhesion. In the later stages of the menstrual cycle, the CVM has a lower pH and increasing progesterone levels cause the CVM to increase in viscosity, increasing mucoadhesion and decreasing mucodiffusion (Adnane et al.  2018 ; Chappell et al.  2014 ). It is also important to note the impact of other factors on CVM. A study by Najmabadi et al. reports that CVM decreases in both quality (defined as increased viscosity and dryness) and quantity as age increases (Najmabadi et al.  2021 ). Since CVM is a protective barrier in the female reproductive tract, the presence of bacteria and infection can also greatly vary the properties of CVM (Vagios and Mitchell  2021 ). Additionally, pregnancy alters CVM qualities due to the formation of the mucus plug, which is a viscous mucus barrier intended to strongly protect the uterus from bacteria (Lacroix et al.  2020 ). All of these changes affect the ability of a system designed to mucoadhere or mucodiffuse to be effective. Gels can be classified into two categories: hydrogels and organogels, both with advantages for drug delivery. Hydrogels are polar, whereas organogels are nonpolar; combining these polar and nonpolar components into a single gel results in a bigel. Bigels are amphiphilic and react differently in nonpolar versus polar environments. The hydrogel component of a bigel enables adhesion within the mucus via electrostatic interactions. The organogel component decreases the amount of water capacity of the gel, thereby reducing overall swelling behavior, and contains drugs within the network for longer, promoting gradual, controlled release (Singh et al.  2014 ). Overall, a bigel can exhibit both mucoadhesive and mucodiffusive properties. This allows bigels to offer a longer retention time within the female reproductive system than other methods (Martin‐Illana et al.  2022 ). It also allows for the incorporation of both nonpolar and polar drugs into the gel itself, allowing for a comprehensive range of drugs applicable for use within the same gel. In the female reproductive tract, bigels can overcome the protective CVM barrier. The mucus layer itself is aqueous, and the glycoprotein surface is rich in lipids (Lacroix et al.  2020 ). The implementation of a bigel allows for the gel to have a favorable interaction in both environments, giving the gel enhanced adhesion and permeation abilities (Singh et al.  2014 ). The mucoadhesive success of a bigel was demonstrated using Carbopol 934 as the hydrogel and sorbitan monostearate as the bigel to administer metronidazole for the treatment of bacterial vaginosis (Singh et al.  2014 ). The sorbitan monostearate organogel promoted mucodiffusion due to the hydrophobicity. Designing vaginal drug delivery systems requires a balance between mucoadhesion and mucodiffusion. The polymeric system needs to be able to both have extended mucosal retention and enhanced mucus penetration to capitalize on the environment of the female reproductive system and have the highest capability of successful drug delivery. Formulations that integrate both mucoadhesion and mucodiffusion such as bigels are promising strategy for overcoming the complex environment of the female reproductive tract and its integral protective barrier, cervicovaginal mucus.

The authors declare no conflicts of interest.

Nanoengineering is the process by which particles from 1 to 100 nm are formed to generate novel materials, such as biomaterials for drug delivery systems (Davis Jr. et al.  2025 ; Mozafari  2020 ). Nano‐engineered materials encompass polymers, liposomes, metals, and other materials. For biomaterials, including polymers, carbohydrates, peptides, and proteins used for biological applications, the surface properties are extremely important because they dictate the interactions with the tissue of interest (Engel et al.  2012 ). Nanocarriers offer several benefits, including increasing the solubility of certain hydrophobic drugs, protecting drugs from degradation, and prolonging their blood circulation (Shi et al.  2023 ). These carriers can be engineered for passive or active targeting of gynecological cancers to reduce systemic side effects. Biomaterials can be used to form a variety of nano‐scale carriers for therapeutic applications. Nanoparticles are comprised of solid materials, are typically spherical, and have distinct physicochemical properties compared to the bulk materials (Mourdikoudis et al.  2018 ). In contrast, nanogels are deformable biomaterials made from cross‐linked networks of polymer chains that swell in aqueous solutions (Soni et al.  2016 ). Targeted nanomaterials are functionalized to achieve higher cell‐ and tissue‐selectivity. For example, antibody‐drug conjugates (ADCs) leverage monoclonal antibodies (mAbs) to selectively target cells (Mungra et al.  2024 ). Currently, lipid‐based nanoparticles, protein‐drug conjugates, and metallic nanoparticles are all US FDA‐approved for therapeutic use. These FDA‐approved nanotherapeutics rely on either passive targeting through the enhanced permeability and retention (EPR) effect or active targeting using ligands to deliver a drug or cargo to the desired site (Rodriguez et al.  2022 ). Chemotherapeutic treatment of gynecological cancer is limited by low stability, poor solubility in serum, lack of biocompatibility, rapid renal clearance, and low tumor specificity (Qasim Almajidi et al.  2024 ). Chemotherapeutics negatively impact fertility in both men and women (Abady et al.  2026 ). Specifically, in women, the use of chemotherapeutics causes premature ovarian failure, infertility, and premature menopause (Markowska et al.  2024 ; Shin et al.  2021 ). Developing alternative or more tumor‐specific therapies can assist in fertility preservation. Passive tumor targeting utilizes the enhanced permeability and retention (EPR) effect, a phenomenon where macromolecules (e.g., nanocarriers) preferentially accumulate in solid tumor tissues due to the leaky vasculature and impaired lymphatic drainage (Figure  2 ) (Rodriguez et al.  2022 ). Solid tumors may develop in the uterine endometrial tissue or the uterine muscle and connective tissues, the ovaries, cervix, or the vaginal wall. This approach can increase bioavailability, enhance tumor drug accumulation, and reduce off‐target effects compared with free drugs. In one in vitro investigation, 24‐EpiBrassinolide assemblies engineered to encapsulate doxorubicin demonstrated enhanced cellular uptake in HeLa cells relative to free drug (Banerjee et al.  2019 ). However, passive targeting remains inefficient and often results in nanocarrier accumulation at sites such as the liver and spleen (Kumar et al.  2023 ). Demonstration of healthy tissue vasculature (top left) which prevents nanoparticle delivery, leaky tumor vasculature (top right) which promotes nanoparticle delivery through the enhanced permeability and retention (EPR) effect. Common female‐linked cancers include breast, ovarian, and endometrial solid tumors (pictured) as well as cervical and vulvovaginal tumors (not pictured). The differences in passive targeting (bottom left) versus active targeting (bottom right) with surface ligands on the nanoparticle and cell surface receptors on the cancer cell. Common surface receptors in female‐linked cancers include ERα, FRα, CD44, HAPB1, and HAPB2. BioRender. Emerging evidence further highlights the limitations of passive tumor targeting in gynecological tumors. In vivo mouse models have demonstrated that the female menstrual cycle can influence nanoparticle accumulation for both ovarian and breast cancer tumors. In these studies, researchers reported two‐fold increases in gold and lipid nanoparticle accumulation in murine ovaries and uteruses during the oestrus (ovulatory) stage compared with the dioestrus (nonovulatory) stages (Poley et al.  2022 ). This variation was shown to differentially impact therapeutic outcomes. In the ovarian cancer mouse models, utilizing the mouse ovarian surface epithelium cell line with luciferase reporter (MOSE‐Luc) in C57BL/6 mice, increased drug accumulation during ovulation improved therapeutic efficacy, whereas in the breast cancer mouse models, utilizing 4T1 murine breast cancer cells transfected with mCherry reporter in BALB/c mice, accumulation in reproductive tissues reduced efficacy due to off‐target distribution. These findings emphasize the need to consider physiological factors such as the menstrual cycle when designing nanomedicines for women. Research is lacking regarding women's health across the lifespan, specifically in that the ovaries are known to have increased fibrosis and stiffness in women over 38 years of age, but similar effects on the endometrium, cervix, and vagina have not been explored (Abady et al.  2026 ). Active targeting uses ligands, antibodies, or proteins with enhanced specificity for the target location (Attia et al.  2019 ). In gynecological cancers, many tumors overexpress receptors, which can be exploited for targeted delivery. Ovarian cancer, for example, commonly overexpresses estrogen receptors, such as ERα, as well as folate receptor FRα. These receptors are key drivers of tumor proliferation and growth. Strategies targeting these overexpressed receptors have been explored to improve delivery (Xie et al.  2023 ). For example, including poly(lactic‐co‐glycolic acid) (PLGA) particles loaded with paclitaxel exhibited greater cytotoxicity and a 3.6‐fold higher cell uptake in SKOV‐3 ovarian cancer cells when modified with a folate conjugation compared to non‐functionalized particles (Luiz et al.  2019 ). By engineering nanocarriers to target features associated with the tumor, chemotherapeutics can be more effectively delivered, minimizing negative side effects while enhancing therapeutic efficacy and therefore significantly increasing the quantity of drug delivered to the target cell compared to passively targeting nanotherapeutics (Attia et al.  2019 ). The total time from inception to FDA approval occurs over a minimum of 12 years (Berezowitz and Givens  2025 ). A major barrier in translating novel nanocarriers to the clinic is the gap between pre‐clinical and clinical outcomes. Although many nanomaterials demonstrate strong efficacy in murine models, they often fail in humans, in part because the enhanced permeability retention (EPR) effect is less pronounced in solid human tumors (Zhao et al.  2025 ). Additionally, translation in gynecological oncology is further constrained by ethical concerns surrounding reproductive health and potential off‐target effects in female‐specific tissues (Yadav and Sharma  2026 ). Initial pre‐clinical screening often occurs in vitro using cell‐based analyses (Clarridge et al.  2022 ). Commonly used cell lines for gynecological cancers include Ishikawa and KLE for Type 1 and Type 2 endometrial cancers, respectively; HeLa cells for cervical cancer, and SK‐OV‐3 and OVCAR‐3 for investigating invasive and drug‐resistant ovarian cancers, respectively (Skok et al.  2021 ). Few studies have isolated tumor cells from patients in ovarian cancer (Zhao et al.  2016 ). These investigations may include cellular uptake and intracellular localization of nanocarriers (Jani et al.  2025 ), viability (Coulter et al.  2024 ; Jani et al.  2025 ; Liu et al.  2025 ; Panwar et al.  2023 ), apoptosis and necrosis (Eder et al.  2022 ; Martinez‐Jothar et al.  2019 ), migration and invasion (Zhao et al.  2016 ), and molecular, genetic, and protein‐level impacts (Capaci et al.  2023 ; Chehade et al.  2020 ; Dixit et al.  2023 ). Although simple to conduct, these assays are limited in their mechanistic depth and do not capture the complexity of three‐dimensional 3D tumor environments in the female reproductive system (Bhattacharjee et al.  2012 ; Salinas‐Vera et al.  2022 ). Combining these approaches provides a more comprehensive understanding of cell death, but they remain limited when using simplified two‐dimensional systems. Recent work has focused on improving pre‐clinical models through the development of three‐dimensional culture systems including spheroids, organotypic cultures, and organoid models. Spheroids are in vitro cultures in which cancer cell lines are grown in low‐adherence tissue culture plastic plates or over inert substrates rather than extracellular matrix (ECM). These models have recently been used in high‐throughput drug screening for cervical and endometrial cancer, which can help to advance the pre‐clinical pipeline for drug investigations of new or repurposed drugs (Cadena et al.  2023 , 2024 ; Salinas‐Vera et al.  2022 ). Organotypic cultures are in vivo systems designed so cells are cultured on commercial Matrigel containing extracellular matrix proteins, enabling partial simulation of the tumor microenvironment. However, Matrigel has high batch‐to‐batch variability limiting reproducibility in research, and the mechanical properties of Matrigel differ from the native tissues, which can limit accuracy (Aisenbrey and Murphy  2020 ). Despite these limitations these models have been used to demonstrate how micelles loaded with anticancer compound, RAPTA‐C, inhibited the invasion of OVCAR‐4 ovarian cancer cells into a model of the omentum. OVCAR‐4 cells are high‐grade serous ovarian adenocarcinoma which have multidrug resistance, and the omentum is an apron‐like fold of fatty tissue and peritoneum that drapes over the intestines and organs in the abdomen. Although the omentum has a protective layer of mesothelial cells that can inhibit cell attachment, ovarian cancer cells can secrete adhesive factors that allow them to attach and spread to other sites (Lu et al.  2019 ). By using a model of the omentum, researchers can better test how therapeutics may inhibit ovarian cancer cells from attaching to the omentum and spreading to other parts of the body. Compared to two‐dimensional cultures, this approach enables a more detailed evaluation of how nanotherapeutics interact with tumor cells in a physiologically relevant context despite the limitations of Matrigel. Finally, organoid models are three‐dimensional miniaturized versions of organs or tissues that are derived from cells with stem potential. Cells with stem potential can self‐organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts in an organoid model. Using patient‐derived models, especially in cancer research, allows researchers to maintain the genetic diversity of the original tumor and therefore better capture the drug sensitivity of the original tumor. Ex vivo patient‐derived explants (PDEs) and patient‐derived xenografts (PDXs) are excellent model types currently being used in the women's health space. PDEs are cultured in matrix systems and mimic the extracellular environment, facilitating drug testing in intact human tumor tissue. Recent works have explored using PDEs to better model endometrial cancer where researchers have been able to develop a rapid low‐cost PDE that would allow for personalized drug testing (Collins et al.  2021 ). Similarly, PDXs are advanced tools that allow researchers to maintain the three‐dimensional structure and cellular diversity of the original tissue. PDXs have recently been used to determine potential novel biomarkers that could be used to better treat the cancer. In one study, researchers reconstructed PDXs from 40 ovarian cancer patients to explore ADP‐ribose polymerase inhibitors (PARPi), Niraparib and Olaparib, in ovarian cancer treatment and determine if the PDX would predict actual patient outcomes. They found that this model was able to more accurately predict PARPi response than currently used biomarkers; however, they also found that the PARPi did not outperform chemotherapeutics like paclitaxel and carboplatin (Chen et al.  2022 ). While these systems are great for maintaining the original tumor architecture there is a lack of reproducibility due to tumor heterogeneity. Together, these approaches highlight the importance of physiologically relevant pre‐clinical models for improving the translation of nanocarriers in gynecological cancer treatment. CD44 is a cell surface glycoprotein that is commonly overexpressed in cancers, including breast, ovarian, cervical, and uterine cancers, and therefore serves as a target receptor in nano‐therapeutics via CD44 antibodies, hyaluronic acid, and Levan (Lee et al.  2023 ; Mutlu et al.  2021 ). For example, hyaluronic acid‐functionalized titanium dioxide (TiO 2 ) nanoparticles that allow for the passive and active targeting of 4T1 murine breast cancer cells (Cheng et al.  2025 ). Hyaluronic acid nanogels were synthesized to deliver cisplatin in combination with the kinase inhibitor gefitinib, resulting in enhanced therapeutic benefit compared with either component alone in vitro (Guo et al.  2024 ). Other studies focusing on the treatment of cervical cancer have shown that incorporating a small molecule drug with hyaluronic acid effectively targeted HeLa cervical cancer cells, whereas a non‐cancer cervical cell line, HCerEpiC cells, exhibited weak cellular uptake (Wang et al.  2025 ). Paclitaxel‐loaded Levan particles were prepared via nanoprecipitation, which resulted in selective binding to cells that expressed the CD44‐receptor. Additionally, the nanoparticles also demonstrated sustained release over 7 days and exhibited long‐term stability (Lee et al.  2023 ). Other techniques for actively targeting cancer cells include antibody‐drug conjugates (ADCs). ADCs are defined as biopharmaceutical agents that contain a monoclonal antibody, a cytotoxic payload (typically a chemotherapeutic), and a linker that connects the antibody to the payload (Dean et al.  2021 ; Huynh et al.  2023 ). One key advantage of ADCs is that the conjugate provides enhanced targeting, thereby reducing systemic toxicity (Huynh et al.  2023 ). ADCs are primarily used to treat cancer and have FDA‐approved formulations to treat the following cancers: breast cancer, urothelial cancer, myeloma, acute leukemia, and lymphoma (Dean et al.  2021 ). The ADC Rinatabart sesutecan (Rina‐S) has advanced to clinical trials in advanced ovarian cancer (Plummer et al.  2020 ). An ADC based on the transtuzumab monoclonal antibody combined with doxorubicin or mertansine for treating HER2‐positive breast cancer selectively targeted HER2‐breast cancer cells in vitro (Huynh et al.  2023 ). Additionally, a cell adhesion molecular 1 (CADM1)‐targeted ADC successfully targeted endometrial carcinoma cells in vitro (Hagiyama et al.  2024 ). In a phase III clinical trial, it was shown to improve the survival of breast cancer patients by increasing the bioavailability of the chemotherapy drugs, enhancing localized targeting, and reducing damage to healthy tissues (Mamounas et al.  2021 ; von Minckwitz et al.  2019 ). Monoclonal antibodies can be further used in ADCs to specifically target CD44 when overexpressed in tumor cells. Click chemistry is a widely used approach for biomaterials to reduce cytotoxic processing, such as photopolymerization or the use of toxic reactants or solvents (Battigelli et al.  2022 ). Additionally, click chemistry is a rapid processing method with high yield, thereby streamlining the production process (Best  2009 ). Using these properties, an ADC was prepared from an antimitotic drug combined with a SNAP‐tag protein and a single‐chain fragment variable region of the CD44 antibody (Mungra et al.  2024 ). This novel ADC selectively targeted breast cancer cells expressing CD44. Specifically, researchers quantified binding to the CD44 receptor in five cell lines and demonstrated that Hs578T (triple‐negative breast cancer) cells had the highest binding, whereas HEK293T (embryonic kidney) and MDA‐MB‐231 (triple‐negative breast cancer) cells showed no binding. Other breast cancer cell lines, MDA‐MB‐468 (metastatic triple negative breast adenocarcinoma) and MCF‐7 (metastatic ductal carcinoma), had some binding, but not as strongly as the Hs578T cells. Additionally, the wells with low to no binding also did not exhibit cytotoxicity in response to the ADC, but the cells that positively expressed CD44 and therefore bound the ADC had greater cytotoxic responses. In addition to ADCs, nanoparticle‐based prodrugs are also a strategy for targeting and treating cancer. Prodrugs are medically inactive precursors to active drug molecules and combination with nanotechnology improves drug stability and bioavailability of poorly soluble drugs (Rautio et al.  2008 ). Nano‐prodrugs have been studied in many types of cancer treatment therapies, such as breast cancer, prostate cancer, and other solid tumors. In one study, a novel nano‐pro‐drug combination was synthesized for the treatment of MDA‐MB‐231 triple negative breast cancer (TNBC) cells and BALB/c mice with 4T1‐luc tumors (Lan et al.  2026 ). The combination successfully inhibited proliferation, migration, and invasion in vitro and suppressed the metastatic lung tumors in vivo. Biomaterials enhance tumor targeting through either the EPR effect or receptor‐mediated binding. This is particularly useful in gynecological tumors that overexpress certain receptors, such as CD44, which then bypass the native, healthy tissue for improved tumor targeting. These methods also reduce systemic toxicity by reducing uptake in non‐cancerous cells and tissues. These investigations support the exploitation of the unique tumor environment to enhance cancer therapeutics.

Stimuli‐responsive, or “smart,” biomaterials have become one of the most prevalent areas in modern drug delivery. Smart biomaterials respond to naturally occurring physiological cues such as changes or differences in pH, temperature, or enzyme activity. These smart hydrogels respond dynamically to changes in their microenvironment, modulating drug release rates and mechanical behavior (Xin and Naficy  2022 ). This function of smart biomaterials is vital in women's health applications where tissues, such as the vaginal mucosa, exhibit distinct chemical and physical conditions that differ from systemic environments (Arvejeh et al.  2025 ). In contrast, traditional biomaterials release drugs via passive diffusion from an area of high concentration within the material to an area of lower concentration in the surrounding tissue, without any external trigger controlling the release rate (Xin and Naficy  2022 ). Through engineering these smart hydrogel materials, drug delivery systems can achieve controlled, localized therapy while minimizing systemic effects (Thirupathi et al.  2022 ). Among the most widely studied classes of smart biomaterials are pH‐responsive materials, because of their ability to adjust their structure and drug‐release behavior in response to acidic conditions. These systems contain ionizable groups, such as —COOH or —NH 2 , that can protonate or deprotonate in response to pH changes, thereby modifying electrostatic repulsion and the hydrogel's swelling behavior (Gao and Xu  2025 ; Xin and Naficy  2022 ). Core swelling theory shows that the ionization state of functional groups like carboxylates or amines directly influences a hydrogel's' mesh size. This means that natural pH changes in tissues such as the vagina, uterus, or tumor ECM can meaningfully alter water uptake and drug diffusion patterns (Koetting et al.  2015 ). Leveraging material speciation as a function of the pKa allows biomaterials to undergo changes as a function of pH changes throughout the human body (Table  1 ), which therefore allows for targeted drug delivery. Of particular relevance to this review, tumor tissue exhibits mild acidity (pH ~6.5–6.8), while the vaginal mucosa is strongly acidic (pH ~3.8–4.5), each providing a unique trigger for protonation‐driven swelling and accelerated drug release (Gao and Xu  2025 ; Xin and Naficy  2022 ). Additionally, the uterus maintains a slightly neutral‐to‐alkaline pH (approximately 6.6–7.6), which shifts throughout the menstrual cycle due to hormone‐regulated changes in uterine fluid composition. These fluctuations create an additional microenvironment in which polymer ionization and release behavior can be finely tuned for pH‐responsive delivery systems. In women's health, pH‐responsive hydrogels show potential due to their charge interactions, enhancing adhesion to mucosal tissues, allowing for localized and prolonged therapy. Some protonated polymer systems have maintained vaginal contact for over 24 h while still sustaining drug release (Permana et al.  2023 ; Torres‐Figueroa et al.  2021 ). Despite their advantages, some natural polymer–based hydrogels still face challenges related to biocompatibility and variability in raw materials, which can complicate consistency and limit translation toward clinical use (Yu et al.  2024 ). Physiological pH throughout the human body. Note that exact values of pH are dependent upon measurement methods and therefore may vary slightly outside of the range cited. The protonated amine groups in chitosan which provide the positive charge for mucoadhesion also enhance swelling in the physiological environment (Xin and Naficy  2022 ). Furthermore, chitosan‐PEG hydrogels released doxorubicin, a potent chemotherapeutic commonly used to treat breast cancer, faster under acidic conditions, such as the tumor microenvironment, confirming a pH‐dependent release (Xin and Naficy  2022 ). Recent work with 2‐(diethylamino)ethyl methacrylate (DEAEMA)‐based nanogels shows a similar pattern, where protonation of tertiary amines under specific conditions drives swelling and leads to efficient loading and intracellular uptake of both siRNA and doxorubicin in SW48 human colorectal cancer cells and Caco‐2 human colon carcinoma epithelial (Huang et al.  2025 ). Like endometrial cancer, colorectal cancer is linked to Lynch syndrome, a set of heritable DNA mismatch repair gene mutations (Olave and Graham  2022 ). Doxorubicin is also used in the treatment of several gynaecologic cancers, including ovarian, endometrial, and certain recurrent cervical cancers, further underscoring the relevance of pH‐responsive chitosan platforms for women's health applications. Additionally, an injectable, β‐glycerophosphate‐cross‐linked chitosan hydrogel with mesoporous silica nanoparticles (MSNs) to co‐deliver the chemotherapeutic 5‐fluorouracil and the mTOR inhibitor everolimus, achieving 70% release of 5‐fluorouracil and 60% release of everolimus over a 10‐day period in acidic pH (Arvejeh et al.  2025 ). Despite their advantages, some natural polymer–based hydrogels still face challenges related to biocompatibility and variability in raw materials, which can complicate consistency and limit translation toward clinical use (Yu et al.  2024 ). Some materials can respond to multiple stimuli simultaneously, thereby enhancing controlled drug delivery. A dual‐responsive poly(N‐isopropylacrylamide‐co‐polyacrylamide), pNIPAM, hydrogel was designed to release at pH 5.0 and 45°C (Thirupathi et al.  2022 ). In addition to the acidic pH of the tumor microenvironment, tumor‐associated hyperthermia occurs following inflammation and healing. This dual mechanism mirrors the conditions observed in cancerous tissues, demonstrating how multiple stimuli can enhance targeting efficacy. Additionally, adjusting monomer ratios and crosslinking density allows for further tuning to the pH‐responsive range by altering the number of ionizable groups, which can in turn expand applications to other tissues such as the vagina or uterus (Gao and Xu  2025 ). Temperature‐responsive hydrogels undergo reversible structural changes under physiological conditions (in situ) to control drug release (Harsanyi et al.  2024 ). Thermo‐responsive hydrogels are generally comprised of synthetic polymers that can leverage injectability, biocompatibility, and localized release (Dewey and Harley  2021 ). These properties make thermos‐responsive materials valuable for cancer therapy and vaginal drug delivery. Polymers such as pNIPAM exhibit a lower critical solution temperature (LCST) of approximately 32°C, transitioning from a hydrophilic liquid to a hydrophobic gel as temperature increases (Piao et al.  2024 ; Xin and Naficy  2022 ). Other injectable formulations exploit this behavior, remaining fluid at room temperature (23°C) but solidifying at body temperature. For example, polymerized high internal phase emulsions (polyHIPEs) have long‐term stability at 4°C and solidify in situ to form scaffolds for tissue regeneration (Moglia et al.  2014 ). These same properties are used in drug delivery, such as a PLGA‐PEG‐PLGA triblock copolymer that transitions from a liquid to a gel at approximately 37°C and was used to locally deliver epidermal growth factor (EGF) as a cervical cancer therapeutic (Piao et al.  2024 ). This hydrogel provided sustained release for over 1 week, and reduced tumor recurrence in NCG mice without systemic toxicity. Another such application was a shape‐memory polymer (SMP) foam which was used for a vaginal stent in which it is a narrow, compressed shape to facilitate insertion and expanding to fill the vaginal cavity upon temperature changes to treat vaginal stenosis (Hicks et al.  2024 ). Likewise, localized delivery to the vagina is achievable using this phenomenon to increase residence time (Coulter et al.  2024 ; Zhang et al.  2024 ). This residence time can be further enhanced by incorporating mucoadhesive polymers, such as pNIPAM and poloxamer (Permana et al.  2023 ; Torres‐Figueroa et al.  2021 ). Enzyme‐responsive hydrogels represent another form of smart material that release drugs in response to biochemical stimuli within the body. Enzyme‐responsive hydrogels are designed with linkages or short peptide sequences that are specifically targeted by enzymes for degradation (Coulter et al.  2024 ). MMP‐2 is an extracellular matrix‐degrading enzyme that is highly expressed in many invasive tumors, including breast cancer. MMP‐2 and MMP‐9 are also overexpressed in several gynaecologic malignancies, including ovarian, cervical, and endometrial cancers, making them attractive biological triggers for localized drug delivery systems (Kessenbrock et al.  2010 ; Roy et al.  2009 ). To target MMP‐2‐expressing tumors, a peptoid‐peptide hybrid hydrogel was developed that remained in the liquid phase until activated by endogenous phosphatases (Coulter et al.  2024 ). Once triggered, the phase transition from liquid to gel occurred. Some of the most novel enzyme‐responsive systems incorporate peptide sequences that are only cleaved when enzymes associated with disease are present. A similar study using an MMP‐2‐responsive peptide hydrogel co‐delivered the chemotherapeutic bufalin and the near‐infrared dye IR820, thereby combining chemotherapy and photothermal therapy (Zhang et al.  2024 ). This enables highly selective drug release in tissues with elevated protease levels, such as tumors or inflamed mucosa (Ulijn et al.  2007 ). These approaches may be particularly valuable in ovarian and endometrial cancers, where localized delivery may reduce off‐target toxicity associated with conventional chemotherapy (Zhang et al.  2024 ). The MMP‐2‐responsive hydrogel self‐assembled under physiological conditions and degraded in the presence of proteolytic enzymes, thereby facilitating sustained delivery and minimizing off‐target effects (Zhang et al.  2024 ). Peptide and peptoid materials also offer structural tunability, as their sequences can be created to respond to specific cleavage sites or motifs. This control makes them applicable to women's health applications where enzyme expression levels may vary throughout the reproductive tract. Enzyme‐responsive systems also show strong potential for vaginal and cervical drug delivery applications, as the vaginal mucosa contains endogenous enzymes and inflammatory mediators that vary during infection, menstruation, and dysbiosis (Monin et al.  2020 ; Wira et al.  2015 ). Hydrogels designed to respond to these biochemical changes may improve the localized residence time within the vaginal cavity (Permana et al.  2023 ). Asadi et al. ( 2024 ) emphasize that natural‐polymer hydrogels in combination with enzyme‐responsive linkages can offer biocompatibility and selective degradability while maintaining mechanical integrity (Asadi et al.  2024 ). Overall, enzyme‐responsive peptide systems represent a promising strategy for women's health because they provide highly selective, localized drug release in gynaecologic cancers and reproductive tract diseases while minimizing premature drug loss and reducing systemic side effects. Hyaluronic acid (HA) is a naturally derived and highly biocompatible polymer widely used in smart hydrogel systems for targeted drug delivery. HA‐based hydrogels can deliver drugs directly to diseased cells while maintaining the high biocompatibility of HA (Luo et al.  2019 ). HA‐based biomaterials are especially useful in women's health applications because HA interacts with several receptors and hyaluronic acid binding proteins (HABPs) that are overexpressed in gynaecologic cancers and inflamed reproductive tissues (Wira et al.  2015 ). HABP1 and other HA‐associated proteins are involved in extracellular matrix remodeling and tumor progression. HABP1 expression has been associated with tumor progression in several cancers (Stern  2008 ). These receptor‐specific interactions can also improve cellular uptake and retention of HA‐functionalized biomaterials in diseased tissues (Luo et al.  2019 ). One of the most studied HA receptors is CD44, which is highly expressed in ovarian, cervical, and endometrial cancers and is associated with tumor progression, metastasis, and chemoresistance (Misra et al.  2015 ). Because of this receptor specificity, HA‐based hydrogels and nanoparticles may accumulate more effectively within tumor tissues through receptor‐mediated interactions. This may improve localized delivery of chemotherapeutics while reducing systemic toxicity. For example, injectable HA hydrogels loaded with doxorubicin were used for breast cancer therapy and showed sustained tumor‐site retention with reduced metastasis in BALB/c mice with tumors derived from the 4T1 murine breast cancer cell line (Shi et al. 2025 ). Although this study focused on breast cancer, similar receptor‐targeting mechanisms may also apply to gynaecologic cancers that overexpress CD44, including ovarian and endometrial cancers (Misra et al.  2015 ). Chemically modified HA can exhibit tuneable degradation and drug‐release kinetics, improving retention and tumor targeting within localized microenvironments (Luo et al.  2019 ). Due to their biocompatibility, mucoadhesive properties, and receptor‐specific targeting ability, HA‐based smart biomaterials remain promising candidates for localized treatment of gynaecologic cancers and other women's health applications. Recent studies are combining multiple stimuli to mimic the complex biochemical and physical cues of mucosal tissues. For example, a dual‐responsive pNIPAM‐co‐pAAM system displays excellent control over drug release compared to a single stimuli‐responsive system (Thirupathi et al.  2022 ). pNIPAM‐co‐pAAM refers to a copolymer of poly(N‐isopropylacrylamide) and polyacrylamide, combining temperature‐responsive and water‐swelling characteristics to tune gel behavior. Similar multi‐responsive systems are also being explored in women's health applications. Thermosensitive and mucoadhesive vaginal hydrogels based on polymers such as poloxamer and chitosan have been developed to improve vaginal retention and localized drug delivery under physiological conditions within the reproductive tract (AlAnsari et al.  2024 ). Other multi‐stimuli systems designed for cervical cancer therapy combine pH–responsive drug release with thermoresponsive gelation to improve localized chemotherapeutic delivery (Piao et al.  2024 ). Additionally, natural‐polymer hydrogels that responded to both temperature and pH achieved greater cytocompatibility and efficacy in breast cancer models (Asadi et al.  2024 ). As research progresses, the integration of multi‐responsive hydrogels targeting enzymes, receptors, and pH and temperature gradients could be the future of therapeutic systems for both cancer and women's health applications. Much of the research presented herein is focused on physics, chemistry, and engineering of materials to achieve a desired response. For clinical translation, the basic and medical sciences must be integrated to advance to subsequent stages of development. Overall, the pathway to translation is slow to ensure the safety and efficacy of materials, and even then, most drugs and drug delivery systems fail before reaching the market. However, the distinct advantage presented in this review is that the basic sciences have determined, through theory and experiment, the physiological properties that make women unique and how drug delivery systems can leverage these properties for enhanced delivery. Biomaterials for women's health offer innumerable potential for advancing science and medicine. These biomaterials are designed to use the properties of the female reproductive system as advantages, rather than barriers. Much of the innovative materials presented fall into the category of engineered nanomaterials, which are 1–100 nm in diameter. These nanomaterials enhance drug delivery beyond conventional therapeutics by increasing bioavailability in target tissues. Furthermore, delivery in the female reproductive system may benefit from the unique mucosal environment. Mucoadhesion of polymers for enhanced retention in the vagina can be leveraged by using cationic particles, which undergo electrostatic and diffusive interactions with the mucus. Furthermore, stimuli‐responsive materials leverage the pH of the vagina and tumors to release cargo under specific pH conditions via protonation and speciation. These phenomena are highly advantageous toward the advancement of women's health solutions.