Thermogel Loaded with Low-Dose Paclitaxel as a Facile Coating to Alleviate Periprosthetic Fibrous Capsule Formation

Medical-grade silicones as implants have been utilized for decades. However, the postoperative complications, such as capsular formation and contracture, have not yet been fully controlled and resolved. The aim of the present study is to elucidate whether the capsular formation can be alleviated by local and sustained delivery of low-dose paclitaxel (PTX) during the critical phase after the insertion of silicone implants. A biocompatible and thermogelling poly(lactic acid- co-glycolic acid)- b-poly(ethylene glycol)- b-poly(lactic acid- co-glycolic acid) triblock copolymer was synthesized by us. The micelles formed by the amphiphilic polymers in water could act as a reservoir for the solubilization of PTX, a very hydrophobic drug. The concentrated polymer aqueous solution containing PTX exhibited a sol-gel transition upon heating and formed a thermogel depot at body temperature. In vitro release tests demonstrated that the entrapped microgram-level PTX displayed a sustained release manner up to 57 days without a significant initial burst effect. Customized silicone implants coated with the PTX-loaded thermogels at various drug concentrations were inserted into the pockets of the subpanniculus carnosus plane of rats. The histological observations performed 1 month postoperation showed that the sustained release of PTX with an appropriate dose significantly reduced the peri-implant capsule thickness, production and deposition of collagen, and expression of contracture-mediating factors compared with bare silicone implants. More importantly, such an optimum dose had an excellent repeatability for the suppression of the capsular formation. Therefore, this study provides a strategic foothold regarding the sustained release of low-dose PTX to alleviate fibrotic capsule formation after implantation, and the microgram-level PTX-loaded thermogel holds great potential as an "all-purpose antifibrosis coating" for veiling the surfaces of various implantable medical devices.