Freeze-dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA

Abstract

Topical vaginal sustained delivery of siRNA presents a significant challenge due to the short residence time of formulations. Therefore, a drug delivery system capable to adhere to the vaginal mucosa is desirable, as it could allow a prolonged delivery and increase the effectiveness of the therapy. The aim of this project is to develop a polymeric solid mucoadhesive system, loaded with lipoplexes, able to be progressively rehydrated by the vaginal fluids to form a hydrogel and to deliver siRNA to vaginal tissues. This study demonstrates the feasibility of entrapping pegylated lipoplexes into a solid matrix system for a prolonged delivery of siRNA into the vagina.

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

“…The loss of deformability of the discs is minimal in the batches incorporating only HPMC and increases with the addition of cyclodextrins or surfactants separately; it is even greater in the combination with both solubilizing agents. This is consistent with other studies that evaluate the deformability of freeze-dried systems based on cellulose derivatives, since adding more substances to the systems increases their loss of elasticity [48].…”

Recent advances in the mucus-interacting approach for vaginal drug delivery: from mucoadhesive to mucus-penetrating nanoparticles

“…Poly(ethylene glycol) (PEG) is a neutral hydrophilic polymer able to minimize mucoadhesive interactions between nanosystems and mucins, allowing a rapid penetration through vaginal mucus [27]. The efficacy of PEG coating on NPs penetration properties is related to its MW and coating grade of NPs surface (Figure 2).…”

“…The film was characterized by suitable mechanical properties for vaginal administration and rapidly disintegrated upon contact with simulated vaginal fluid, releasing the loaded NPs. A freeze-dried solid vehicle based on the mucoadhesive polymer hydroxyethyl cellulose (HEC) was employed by Furst et al [27] to release 'mucus-penetrating' lipoplexes, which are LPs encapsulating siRNA, densely coated with PEG. The release of lipoplexes from HEC matrix depended on HEC concentration: the higher the HEC concentration, the lower the NPs diffusion rate.…”

A Polymer Chemistry Point of View on Mucoadhesion and Mucopenetration

“…PEG containing hydrogels are 3D polymeric matrices capable of swelling under aqueous conditions. When exhibiting mucoadhesive properties, hydrogels have potential applications for instance in vaginal drug delivery, which is an excellent form of mucosal drug delivery due to the avoidance of the gastrointestinal absorption and of the hepatic first‐pass metabolism . PEG‐containing hydrogels have also been used as animal tissue mimetic in mucoadhesion studies …”