In Vitro and Ex Vivo Evaluation of Novel Methacrylated Chitosan-PNIPAAm-Hyaluronic Acid Hydrogels Loaded with Progesterone for Applications in Vaginal Delivery.

Miscarriage is defined as the loss of a pregnancy before 24 weeks and administration of progesterone in pregnancy has considerably decreased the risk of premature birth. Progesterone (PGT) starting from the luteal phase stabilizes pregnancy, promotes differentiation of the endometrium, and facilitates the implantation of the embryo. Within the present study, novel hybrid hydrogels based on chitosan methacrylate (CHT), hyaluronic acid (HA), and poly(N-isopropylacrylamide) (PNIPAAm) for vaginal delivery of progesterone were evaluated. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) for structural identity assessment and evaluation of their morphological aspects. The ability to swell, the release capacity, enzymatic degradation, cytotoxicity, and mucoadhesion were also reported. The characterized hydrogels demonstrated mucoadhesive properties in contact with the vaginal tissue of swine and bovine origin as substrates, and biodegradability and controlled release in a simulated vaginal environment. Cytocompatibility tests confirmed the ability of the hydrogels and progesterone to support cell viability and growth. The results showed pH-dependent behavior, controlled drug release, good cytocompatibility, and mucoadhesive properties. The hydrogels with higher chitosan amounts demonstrated better bioadhesive properties. This study provides insights into the potential of these hydrogels for the controlled vaginal delivery of progesterone, with promising therapeutic effects and no cytotoxicity observed. The experimental results indicated that a composition with a moderate content of PNIPAAm was suitable for the controlled delivery of progesterone.

Development of Vaginal Carriers Based on Chitosan-Grafted-PNIPAAm for Progesterone Administration.

Chitosan-based hydrogels possess numerous advantages, such as biocompatibility and non-toxicity, and it is considered a proper material to be used in biomedical and pharmaceutical applications. Vaginal administration of progesterone represents a viable alternative for maintaining pregnancy and reducing the risk of miscarriage and in supporting the corpus luteum during fertilization cycles. This study aimed to develop new formulations for vaginal administration of progesterone (PGT). A previously synthesized responsive chitosan-grafted-poly (N-isopropylacrylamide) (CS-g-PNIPAAm) was formulated in various compositions with polyvinyl alcohol (PVA) as external crosslinking agent to obtain pH- and temperature-dependent hydrogels; the hydrogels had the capacity to withstand shear forces encountered in the vagina due to its mechanism of swelling once in contact with vaginal fluids. Three different hydrogels based on grafted chitosan were analyzed via Fourier-transform infrared spectroscopy (FTIR), swelling tests, in vitro drug release, and bioadhesion properties by TA.XTplus texture analysis. A higher amount of PVA decreased the swelling and the bioadhesion capacities of the hydrogel. All hydrogels showed sensitivity to temperature and pH in terms of swelling and in vitro delivery characteristics. By loading progesterone, the studied hydrogels seemed to possess even higher sensitivity than drug-free matrices. The release profile of the active substance and the bioadhesion characteristics recommended the CS-g-PNIPAAm/PVA 80/20 +PGT (P1) hydrogel as a proper constituent for the vaginal formulation for progesterone administration.