Abstract
Vaginal drug delivery has gained significant interest due to its numerous advantages, such as good blood flow, bypassing the first-pass effect, low systemic side effects, and potential for sustained release of pharmaceuticals. Initially targeting contraception and local effects from antibacterial, antifungal, and antiviral agents, recent advancements have broadened its scope. Notably, microbicide formulations showed promise against sexually transmitted diseases, offering superior protection and effective hormone therapies due to the vagina’s large surface area and high permeability. The main agents used in vaginal delivery include contraceptives, prostaglandins, steroids, and antimicrobial substances, administered through tablets, suppositories, ointments, gels, creams, and vaginal rings. However, challenges such as slow dissolution and short residence time necessitate novel delivery systems. Mucoadhesive polymers are particularly valuable for enhancing drug absorption and extending treatment options. Comparative studies indicate that vaginal absorption of drugs like human growth hormone and insulin surpasses other parenteral routes. The development of standardized in vitro and in vivo testing methods remains crucial due to the diverse drug systems. While vaginal drug delivery offers benefits, such as high vascularization, low enzymatic activity, and increased bioavailability, it also faces drawbacks, including limited drug compatibility, sensitivity to vaginal pH, patient compliance issues, and potential local irritation. This review aims to elucidate the pathway, propose standardized methods for specific therapeutic areas, and highlight novel formulations like hydrogels and lipid nanoparticles for treating various diseases.
Introduction
Vaginal drug delivery has garnered significant interest over the centuries due to its unique physiological and pharmacolog ical advantages. This route bypasses the first-pass metabolism, ensuring good blood flow, low systemic side effects, and the potential for sustained drug release. Initially focused on con traception and local treatments for bacterial, fungal, and viral infections, the scope of vaginal drug delivery has expanded, with microbicide-based formulations showing promise against sexually transmitted diseases like HIV. Compared to traditional prevention methods, these formulations offer superior protection and systemic effects due to the large surface area, permeability, and high blood supply of the vagina, making it effective for hormone replacement therapies and contracep tion [1, 2]. It is of great importance that vaginal drug delivery systems ensure their safety, efficacy, and patient acceptability. Physicochemical properties, such as particle size, pH, viscosity, and drug solubility, play a key role in mucosal penetration, retention, and controlled drug release. Mucoadhesion and permeability are crucial for sustained local or systemic absorption, while an optimal release profile minimizes dosing frequency. Biocompatibility is another critical factor, as formulations must be nontoxic, nonirritating, and microbiome-friendly to maintain vaginal health. Additionally, microbiological quality must be ensured through sterility or appropriate preservative systems, particularly in multi-dose formulations. Stability is also essential, as both physical and chemical properties must remain consistent throughout the product’s shelf life. Lastly, patient acceptability factors, such as ease of application and minimal leakage, are important for adherence to treatment and overall user experience [3–5].
![Figure 1.(a) Viscosity (Pa*s) of the two commercially available pharmaceutical hydrogels, Gynodaktarin and Lubrilan, CVM and the three HEC-hydrogels tested by Furst et al. before lyophilization and after rehydration, (b) mucoadhesive strength of hydrogels in comparison to sponges and (c) adhesion energy (N*mm) [21].](https://www.pharmaexcipients.com/wp-content/uploads/2025/07/Figure-1sd.jpg)
substances. These agents are delivered through various forms, such as tablets, suppositories, ointments, gels, creams, and vaginal rings. Despite their efficacy, these formulations often suffer from slow dissolution and short residence times, necessitating the development of novel delivery systems. The vaginal mucosal layer’s mucoadhesive properties are exploited using mucoadhesive polymers to enhance systemic delivery and expand treatment possibilities. Enhanced absorption of pharmacological molecules like human growth hormone, insulin, and steroids has been observed when administered vaginally compared to other parenteral routes [6, 7].
An interesting property of the organ under considera tion is the mucosal layer that it presents, which makes the mucoadhesiveness of formulation an important property. Hence, mucoadhesive polymers are commonly used to establish a modification of the dosage form and achieve a systemic delivery through the vaginal mucosa and, thus, extend the range of possible treatments to be performed by this administration route. When comparing the vaginal absorption of pharmacological molecules, such as human growth hormone, insulin, or steroids, with other parenteral routes, an enhanced absorption can be observed [8, 9]. Furthermore, in vitro and in vivo testing methodologies play an important role in the progress of the vaginal drug delivery. Nevertheless, the wide variety of drug systems results in the difficult development of standardized testing methods [10].
Favourable properties of the vaginal administration route can be summarized as effective for orally inactive drugs, high
vascularization, low enzymatic activity, prolonged release, increased bioavailability, the avoidance of the first-pass me
tabolism, quick onset of action, possible self-medication, low systemic side effects, and a lower dose is used in compar
ison to the oral route of administration. Nonetheless, only few drugs can be administered, the sensitivity of the pharma
ceutical agent to vaginal pH is an important factor to consider, change in drug absorption as well as gender-specific,
patient incompliance, and local irritation of drugs are some drawbacks that are under scope [11–14].
This review aims to elucidate the vaginal drug delivery pathway and propose modifications to standardized methods for specific therapeutic areas. It also highlights novel drug formulations, such as hydrogels, polymer-based nanocarriers, lipid nanoparticles, and liquid crystals, and their application in treating various diseases. Nanocarriers offer significant advantages over conventional carriers for vaginal drug delivery, primarily due to their ability to enhance drug solubility, prolong retention time, and provide controlled release. Their nanoscale size allows for better mucosal penetration and interaction with vaginal epithelial cells, improving bioavailability. Additionally, nanocarriers can be engineered for targeted delivery, reducing systemic absorption and minimizing side effects. In contrast, conventional carriers, such as gels or creams, often exhibit rapid drug release and limited retention, leading to frequent reapplication and variable therapeutic outcomes. While traditional formulations remain widely used due to their ease of production and cost-effectiveness, nanocarriers represent a promising alternative for achieving more efficient and patient-friendly vaginal drug delivery [15, 16]. Despite its potential, many aspects of vaginal drug delivery require further research and development to realize its full potential.
Download the full article as PDF here Exploring the potential of vaginal drug delivery: innovations, efficacy, and therapeutic prospects
or read it here
Excipients mentioned in the paper: chitosan, PLGA, Carbopol SF, Eudragit RL 100
Eva Sanchez Armengol, Florina Veider, Gioconda Millotti, Gergely Kali, Andreas Bernkop-Schnürch, Flavia Laffleur, Exploring the potential of vaginal drug delivery: innovations, efficacy, and therapeutic prospects, Journal of Pharmacy and Pharmacology, 2025;, rgaf045, https://doi.org/10.1093/jpp/rgaf045
