In situ-forming and pH-responsive hydrogel based on chitosan for vaginal delivery of therapeutic agents

Abstract

One of the important routes of drug administration for localized delivery of contraceptives and cervical cancer treatment agents is vaginal canal. Due to the low pH of vagina, a pH-responsive drug delivery system was developed. This hydrogel was synthesized based on a mucoadhesive biopolymer, chitosan (CS), that promotes the interaction between the hydrogel and mucosal surface of the vagina, potentially increasing the residence time of the system. This injectable hydrogel was formed via acid-labile Schiff-base linkages between free amine groups and aldehyde functionalities on modified chitosan. A novel approach was taken to add aldehyde functionalities to chitosan using a two-step reaction. Two types of slow and fast degrading hydrogels were prepared and loaded with iron (II) gluconate dihydrate, a non-hormonal spermicide, and doxorubicin hydrochloride, an anti-cancer drug. The release profiles of these drugs at different pH environments were assessed to determine the pH-dependent release mechanism. Mechanical properties, swell-ability and degradation rate of these matrices were studied. The cross-linking density of the hydrogel as well as pH changes played an important role in the characteristic of these hydrogels. The hydrogels degraded faster in lower pH, while the hydrogel with lower cross-linking density showed longer gelation time and faster degradation rate compared to the gel with higher cross-linking density. In vitro cytotoxicity assessment of these hydrogels in 48 h indicated the non-toxic effect of these hydrogels toward mesenchymal stem cells (MSCs) in the test period.

Chitosan and Aloe vera gel formulations as wound healing agents in episiotomy

“…The cell lines used in their study were lymphoblastic and uterus epithelial cell lines (MT-2, HEC-1A). Similarly, Jalalvandi and Shavandi (2018) found percentages of cell viability (MSCs, passage 5) greater than 80% for chitosan-gluconate dihydrate and doxorubicin hydrochloride gels. As illustrated in Figure 5, the three formulations exhibited a decrease in apparent viscosity with an increase in the shear rate.…”

Vaginal Administration of Contraceptives

“…Until the 1920s, the vagina was considered a site for the delivery of locally acting drugs only. However, this organ proved to be of great importance for systemic drug delivery, uterine targeting, or even vaccination [28,29] due to its large surface area, a dense network of blood vessels, and permeability to a wide range of compounds [30]. Topical delivery to the vaginal mucosa has many significant applications for preventing human immunodeficiency virus (HIV) and other STDs, mucosal vaccines, treatment of various sexually transmitted infections (STIs), and maintenance of reproductive health.…”

“…High levels of fatty acids present in human sperms make these cells susceptible to the free radical species upon exposure to iron gluconate. This encourages constant formation and decomposition of lipid peroxides and eventually causes structural damage, a decline in metabolic activity, and spermicidal effect [29,137]. Han et al designed two different vaginal rings composed of acacia gum or non-biodegradable hydrogel of 2-hydroxyethyl methacrylate and sodium methacrylate.…”

Injectable Hydrogels for Cancer Therapy over the Last Decade

“…SCS was combined with oxCS [221] or oxALG [222] to obtain pH-responsive injectable hydrogels for DOX sustained release. Other examples of CS derivatives include GTMACS [223] and CS-CAT [224], used for DTX or DOX/DTX combination therapy, respectively.…”