Vaginal Polyelectrolyte Layer-by-Layer Films Based on Chitosan Derivatives and Eudragit® S100 for pH Responsive Release of Tenofovir

Abstract

Women are still at high risk of contracting the human immunodeficiency virus (HIV) virus due to the lack of protection methods under their control, especially in sub-Saharan countries. Polyelectrolyte multilayer smart vaginal films based on chitosan derivatives (chitosan lactate, chitosan tartate, and chitosan citrate) and Eudragit® S100 were developed for the pH-sensitive release of Tenofovir. Films were characterized through texture analysis and scanning electron microscopy (SEM). Swelling and drug release studies were carried out in simulated vaginal fluid and a mixture of simulated vaginal and seminal fluids. Ex vivo mucoadhesion was evaluated in bovine vaginal mucosa. SEM micrographs revealed the formation of multilayer films. According to texture analysis, chitosan citrate was the most flexible compared to chitosan tartrate and lactate. The swelling studies showed a moderate water uptake (<300% in all cases), leading to the sustained release of Tenofovir in simulated vaginal fluid (up to 120 h), which was accelerated in the simulated fluid mixture (4–6 h). The films had high mucoadhesion in bovine vaginal mucosa. The multilayer films formed by a mixture of chitosan citrate and Eudragit® S100 proved to be the most promising, with zero toxicity, excellent mechanical properties, moderate swelling (<100%), high mucoadhesion capacity, and Tenofovir release of 120 h and 4 h in vaginal fluid and the simulated fluid mixture respectively.

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

“…This contributed to a rapid drug release. Cytotoxicity experiments deduced that citric acid and ES100 were non-toxic and demonstrated little damage to mucosal integrity [ 123 ].…”

“…Apart from its mucoadhesive properties, chitosan is capable of showing both thermo-responsive and pH-responsive characters [ 106 , 112 , 123 ]. Ionic cross-linking agents (e.g., β-glycerophosphate), and diluted acid (e.g., citric acid) are added to allow the gelation of chitosan, improve viscoelastic and mechanical performance of designed formulations [ 123 , 175 , 176 , 177 ]. These polymers are useful in the development of drug-delivery system due to their good biodegradability, biocompatibility, low toxicity, and good solubilizing capacity [ 112 ].…”

Amino Functionalized Micro-Mesoporous Hybrid Particles for the Sustained Release of the Antiretroviral Drug Tenofovir

“…The drug adsorption capability can be also tuned depending on its degree of functionalization showing a linear response in both the adsorption characteristic as in the drug releasing capability with the amount of free amino groups in surface forming a monolayer. In our group, several mucoadhesive vaginal formulations have been already developed for the sustained release of TFV [22,24,25]. After the incorporation of the particles, the next step for the consecution of a ready-to use mucoadhesive vaginal formulation will be the determination of the behavior of the composite gel in in-vivo and in-silico experiments, as well as the possibility to manufacture these formulations in a cheap and fast manner for better accessibility to all the collectives potentially affected by VIH disease.…”

“…These hybrid particles are intended to take part of a mucoadhesive vaginal composite, as described by Veiga-Ochoa et al [21][22][23][24][25][26]. After selecting the appropriate carrier, it must be included into the vaginal formulation for in-vivo tests, processability and comfortability assays.…”

Mucoadhesive Vaginal Discs based on Cyclodextrin and Surfactants for the Controlled Release of Antiretroviral Drugs to Prevent the Sexual Transmission of HIV

“…The inclusion of cyclodextrins in these formulations performs numerous functions: 2HPβCD modulates the release of TFV, significantly improves the mechanical properties of the formulations (without which they would be too fragile to administer), and particularly increases the adhesiveness of the formulation to the vaginal mucosa, which is essential for it to be retained in the vaginal environment until all of the drug is released. If we compare the adhesiveness force of the developed formulations to vaginal films developed for the administration of antiretroviral drugs, we can appreciate that the force required to detach both formulations from the vaginal mucosa is really similar [68]. Cyclodextrins are also considered to play a fundamental role in counteracting the cytotoxicity of SDS.…”