Thermosensitive Hydrogel Of Hydrophobically-modified Methylcellulose And Its Properties For Drug Delivery

Hydrogels with the advantages of prolonging drug release and administrationconvenience are necessary for intravaginal drug delivery system to prevent sexualtransmission of HIV and other vaginal infections. In this study, the methylcellulosemodified by stearic acid (MCS) was synthesized by esterification, and the injectablethermosensitive hydrogels of MCS aqueous solutions for intravaginal drug deliverywere prepared. The grafting polymer was characterized by1H-NMR and the resultshowed that the grafting polymer was obtained with designed structure. Although theintroduction of stearyl could greatly reduce the Sol-to-Gel phase transitiontemperature of MC solutions and the gelation temperature decreased with theincrement of concentration of MCS, but still higher than40oC. Higher concentrationNaCl could efficiently decrease the gelation temperature of MCS solutions, at thesame time also leads to mucosal irritation. In order to adjust the gelation temperatureof the MCS aqueous solutions, two methods had been developed in this thesis.Firstly, we used0.05M phosphates with pH in the vaginal environment (pH,4.5~5.5) cooperating with NaCl to adjust the gelation of MCS solutions. We foundthat the combination of phosphates could decrease the viscosity and the gelationtemperature of the MCS solutions. CHO cells growth situations on the hydrogelproved that MCS thermosensitive hydrogel with2wt%NaCl had better celladhesivity properties and biocompatibility. The in vitro cytotoxicity and in vivomucosal irritation were investigated and the results showed that MCS hydrogel wasnon-toxic and safe for intravaginal drug delivery. Significantly, the release studiesrevealed that MCS hydrogel could control hydrophilic drug TFV sustained releasefor10h without burst release.Secondly, nano-cellulose (NC) colloidal was used to adjust the gelation of MCSsolutions. We used new method to prepare uniform NC colloidal solution and mixedwith MCS solution, and then added0.05M phosphates to tune the pH. Thethermogelling properties and rheology were evaluated and the results showed thatthe blending solutions containing2wt%MCS and0.2wt%NC could form ahydrogel at34oC without NaCl. The results of the release studies indicated thatthermosensitive hydrogel had controlled release properties for both hydrophilic drugTFV and macromolecular drug bovine serum albumin (BSA). The results of cytotoxicity assay indicated that the MCS/NC blending hydrogel was non-toxic.