A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy

Abstract

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

Injectable Nanosponge-Loaded Pluronic F127 Hydrogel for Pore-Forming Toxin Neutralization

“… 25–27 Recently, a variety of thermosensitive hydrogels have been developed, such as Pluronic F127, poly(N-isopropylacrylamide) and methylcellulose. 28 , 29 Pluronic F127, also named Poloxamer 407, is an FDA-approved novel temperature-sensitive hydrogel material that has been used for drug delivery and wound healing. 30–32 Compared to chemical cross-linking hydrogels, the pharmaceutical formulation of the Pluronic F127 hydrogel is simple and completely relies on physical methods without requiring chemical cross-linking agents, thus improving safety and reducing production costs.…”

Hybrid Injectable Sol-Gel Systems Based on Thermo-Sensitive Polyurethane Hydrogels Carrying pH-Sensitive Mesoporous Silica Nanoparticles for the Controlled and Triggered Release of Therapeutic Agents

“…Additionally, they can be easily loaded with therapeutic agents, which are then locally released over time in a sustained and controlled way. Interestingly, in the case of thermo-sensitive hydrogels based on amphiphilic polymers, both hydrophilic and hydrophobic drugs can be easily encapsulated at high concentration by exploiting the arrangement of the polymeric chains into micelles, which are also the driving-force for system transition from the sol to the gel state (Xi et al, 2014;Boffito et al, 2016Boffito et al, , 2019aAnggelia et al, 2019). Payload release from thermo-sensitive hydrogels is usually driven by passive diffusion, swelling/erosion or the co-presence of both diffusion and swelling/erosion phenomena (Huang et al, 2019).…”

The Advantages of Polymeric Hydrogels in Calcineurin Inhibitor Delivery

“…Studies were performed on different delivery systems for the administration of TAC, such as mPEG-poly(lactic acid) nanoparticles [83], poly (lactide-co-glycolide) microspheres [129], and triglycerol monostearate hydrogels [130]. Recently, a mixed PolyHy system based on thermosensitive polypeptides and poloxamer was proposed to develop a sustained release reservoir for the delivery of subcutaneously administered TAC in an in vivo model [131]. In addition, the rational design of two hydrogelators was reported to establish an easy method for the release of TAC that induces an immune response to overcome the organ transplant rejection in an animal model [132].…”