Reducing cytotoxicity and fabricating mucoadhesivity of pluronic F127 in situ gels by xyloglucan (a natural polysaccharide)

Xyloglucan from the seed of Tamarindus indica (TSX) is a natural polysaccharide widely used as a food additive and a cosmetic ingredient. It comprises (1 – 4)-β-D-glucan backbone, with three of every four glucose residues substituted with (1 – 6)-α-D-xylose and some xylose residues are substituted with (1 – 2)-β-D-galactose. TSX has various pharmacological activities including antitumor and immune stimulating activity, it can reduce UV-induced repression of the delayed type hypersensitivity response and promote skin regeneration by direct influence on cell proliferation. Unmodified TSX cannot form gel but it has suitable properties for use in pharmaceutical formulations such as biocompatibility, biodegradability and mucoadhesivity. The aim of this study was to prepare the blends of TSX and Pluronic F-127 (PF) to produce mucoadhesive in situ hydrogels with possibility to reduce cytotoxicity of PF. Aqueous solutions of PF (> 15 wt%) are known to undergo thermogelling upon heating. However PF at high concentrations that forms gel is cytotoxic. The thermoresponsive in situ hydrogels were prepared from co-solutions of 18 and 20 wt% PF with 0.1 wt % TSX (18PF/0.1TSX and 20PF/0.1TSX). Based on MTT assay on MC3T3-E1 cells, extractables released from PF/0.1TSX are cytocompatible with similar cell viability to the control (culture medium) whereas those from PF are cytotoxic with cell viability of 54 – 60% compared with the control. Therefore the addition of 0.1TSX results in a significant decrease cytotoxicity of PF. Furthermore PF/0.1TSX gels exhibit improved mucoadhesive strength against mucin compared with PF gels. According to micellization and gelation temperatures analyses using test tube inversion, DSC and rheological measurements, 18PF/0.1TSX and 20PF/0.1TSX are solution at room temperature and can turn to gel at body temperature. Therefore these PF/0.1TSX blends may be useful as injectable thermally responsive mucoadhesive gel for sustained drug delivery.