Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation.\nHowever, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection\ndosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver\ntacrolimus. The copolymers, which consist of poloxamer and poly(l-alanine) with l-lysine segments\nat both ends (P-Lys-Ala-PLX), are able to carry tacrolimus in an in situ gelled form with acceptable\nbiocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding\nPluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain\nsuitable drug levels in animals with transplants. Under this formulation, the in vitro release of\ntacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model\nshowed that rejection from skin allotransplantation was prevented for at least three weeks with one\nsingle administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus\ndemonstrates advancement in immunosuppressive therapy.
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