Abstract
Tacrolimus (FK506) is a common immunosuppressive drug that is capable of suppressing acute rejection reactions, and is used to treat patients after allotransplantation. A stable and suitable serum concentration of tacrolimus is desirable for better therapeutic effects. However, daily drug administration via oral or injection routes is quite inconvenient and may encounter drug overdose or low patient compliance problems. In this research, our objective was to develop an extended delivery system using a thermosensitive hydrogel of poly ethylene glycol, D,L-lactide (L), and ϵ-caprolactone (CL) block copolymer, mPEG-PLCL, as a drug depot. The formulation of mPEG-PLCL and 0.5% PVP-dissolved tacrolimus was studied and the optimal formulation was obtained. The in vivo data showed that in situ gelling is achieved, a stable and sustained release of the drug within 30 days can be maintained, and the hydrogel was majorly degraded in that period. Moreover, improved allograft survival was achieved. Together, these data imply the potential of the current formulation for immunosuppressive treatments.
Highlights
Hydrogels are formed by crosslinking hydrophilic polymers, either through chemical or physical interactions
In our previous study [13], we successfully developed a thermosensitive mPEG-amino hydrogel for sustained release of a hydrophobic drug, which is tacrolimus
The synthesized mPEG-PLCL was characterized by 1H Nuclear Magnetic Resonance (1H-NMR), Gel Permeation Chromatography (GPC), and FTIR
Summary
Hydrogels are formed by crosslinking hydrophilic polymers, either through chemical or physical interactions They can be applied to many biomedical needs, such as drug delivery and tissue engineering [1,2,3,4,5,6,7,8]. Thermosensitive hydrogels synthesized from poly (ethylene glycol)-polyester copolymers are suitable for biomedical applications due to their good biocompatibility and gel-forming properties [11]. The degradation rates of this type of hydrogels were very slow, so the depot persisted more than 3 months It raises concerns about fibrosis formation at the injected site [14,15]. Thermosensitive hydrogel methoxy-poly(ethylene glycol)-co-poly(lactic acid)-poly(e-caprolactone), mPEG-PLCL, was examined for its suitability as a drug carrier
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