PHA-Based Thermogel as a Controlled Zero-Order Chemotherapeutic Delivery System for the Effective Treatment of Melanoma.

Promising applications of poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] (PHBHx) in tissue engineering have been extensively investigated. However, the application of PHBHx in drug delivery has been rarely explored due to its hydrophobic property, limited functionality, and the absence of active groups for reaction. In this work, PHBHx has been functionalized and copolymerized with poly(ethylene glycol) (PEG) and polypropylene glycol (PPG) oligomers to provide a series of novel PHBHx incorporated polyurethanes (PHxEP). In vitro docetaxel (DTX) release showed that DTX loaded thermogel can achieve sustained, zero-order release of DTX, that is, constant 10% release of the payload up to 10 days, which is unique and different from other systems previously reported. The inhibition effect of DTX loaded thermogel on solid tumors was evaluated using mouse tumor models, and its biosafety was evaluated. DTX-loaded thermogel showed enhanced antimelanoma effect on melanoma solid tumors compared to the free DTX drug and no apparent harm to other tissues including liver, heart, spleen, kidney, and lung tissues. The results indicated that the PHxEP-based thermogel can be a hopeful drug delivery candidate for sustained and constant delivery of anticancer drugs. It is the first time that the functionalized PHBHx-based water-soluble thermogels have been reported as the drug carrier for DTX release.