Potential of mucoadhesive chitosan glutamate microparticles as microbicide carriers – antiherpes activity and penetration behavior across the human vaginal epithelium

Abstract

Chitosan glutamate (gCS) spray-dried microparticles appear promising carriers to overcome challenges associated with vaginal microbicide delivery. This study aimed at elucidating the penetration and mucoadhesive behavior of developed gCS multiunit carriers with zidovudine (ZVD) as a model antiretroviral agent in contact with excised human vaginal epithelium followed with an examination of in vitro antiherpes activity in immortal human keratinocytes HaCaT and human vaginal epithelial cells VK2-E6/E7. Both ZVD dispersion and placebo microparticles served as controls. Microparticles displayed feasible (comparable to commercial vaginal product) mucoadhesive and mucoretention characteristics to isolated human vaginal tissue. Ex vivo penetration studies revealed that gCS increased the accumulation of active agent in the vaginal epithelium but surprisingly did not facilitate its penetration across human tissue. Finally, the obtained antiviral results demonstrated the potential of gCS as an antiherpes adjunctive, whose mode of action was related to blocking viral attachment.

Chitosan/Pomegranate Seed Oil Emulgel Composition as a New Strategy for Dermal Delivery of Hydrocortisone

“…This observation shows that the greater amount of CS in a formulation is a prerequisite for improving tissue retention of the model anti-inflammatory agent. The obtained findings are in accordance with our previous studies on vaginal CS multiunit carriers in which higher amounts of CS in the formulations facilitated the tissue accumulation of the microbicide agent [37]. Notably, a higher HTZ tendency to accumulation was observed in the studies using E-2 (p < 0.01), in which a faster rate of drug dissolution was simultaneously observed (Figure 2).…”

Ovarian Follicular Growth through Intermittent Vaginal Gonadotropin Administration in Diminished Ovarian Reserve Women

“…In recent years, vaginal drug administration has been broadened beyond the treatment of local vaginal infections. Spray-dried microparticles with chitosan glutamate multiunit carriers of zidovudine were developed to facilitate microbicide delivery for antiherpes activity in the human vaginal epithelium [63]. More promising, in the fight against HIV/AIDS, polymeric nanoparticles and freeze-dried bigels have been shown to enhance the distribution and retention of promising antiretroviral compounds in the vaginal mucosa [5,6,64].…”

Recent Reports on Polysaccharide-Based Materials for Drug Delivery

“…The microcrystalline CS is characterized by better bioactivity and sorption than chitosan, while the formulation could be applied as an effective dental dressing. A different use for CS microparticles was demonstrated by Szymańska et al [ 74 ]. A water-soluble chitosan derivative, CS glutamate, was mixed with antiretroviral drug–zidovudine–solution to obtain mucoadhesive microparticles for vaginal applications.…”