Controlled release of transforming growth factor-beta receptor kinase inhibitor from thermosensitive Chitosan-based hydrogel: application for prevention of capsular contracture.

ABSTRACT

BACKGROUND: Capsular contracture has become the most common complication associated with breast implant. Transforming growth factor-beta (TGF-ß) is well known for a prominent role in fibrotic diseases. Due to the critical role of TGF-ß in pathogenesis of capsular formation, we utilized thermosensitive C/GP hydrogel to controlled release of TGF-ß receptor kinase inhibitor (SD208) and investigated their effects on capsular contracture. METHODS: In vitro degradation and drug release of C/GP hydrogel were performed. Twenty-four rabbits underwent subpanniculus implantation with 30 ml smooth silicone implants and were randomly divided into four groups as follows Group 1 received saline solution; Group 2 received SD208; Group 3 received SD208-C/GP; Group 4 received C/GP. At 8 weeks, the samples of capsular tissues were analyzed by hematoxylin and eosin and immunohistological staining. The mRNA expression of collagen III and TGF-ß1 was detected by RT-PCR assay. RESULTS: C/GP hydrogel could be applied as an ideal drug delivery vehicle which supported the controlled release of SD208. SD208-C/GP treatment showed a significant reduction in capsule thickness with fewer vessels. The histological findings confirmed that the lower amounts of inflammatory cells and fibroblasts infiltrate in SD208-C/GP group. In contrast, typical capsules with more vessel predominance were developed in control group. We did not observe the same inhibitory effect of SD208 or C/GP treatment on capsular contracture. Moreover, SD208-C/GP therapy yielded an evident down-regulation of collagen III and TGF-ß1 mRNA expression. CONCLUSIONS: This study demonstrated that controlled release of TGF-ß receptor kinase inhibitor from thermosensitive C/GP hydrogel could significantly prevent capsule formation after mammary implants.