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Thermogel Loaded with Low-Dose Paclitaxel as a Facile Coating to Alleviate Periprosthetic Fibrous Capsule Formation
Version 2 2018-08-28, 12:05
Version 1 2018-08-24, 13:38
journal contribution
posted on 2018-08-13, 00:00 authored by Jiabin Luan, Zheng Zhang, Wenjia Shen, Yipei Chen, Xiaowei Yang, Xiaobin Chen, Lin Yu, Jian Sun, Jiandong DingMedical-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.
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Alleviate Periprosthetic Fibrous Capsule Formation Medical-grade siliconesreleasefibrotic capsule formationentrapped microgram-level PTXacidperi-implant capsule thicknesspoly1 month postoperationmicrogram-level PTX-loaded thermogelCustomized silicone implantssubpanniculus carnosus planesilicone implantscapsular formation
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