Protective role of transforming growth factor-Β3 (TGF-Β3) in the formation of radiation-induced capsular contracture around a breast implant: In vivo experimental study

• Published in: International journal of pharmaceutics 2024-11, Vol.665, p.124715, Article 124715
• Main Authors: Sezer, Aysima, Ozalp, Hulya, Imge Ucar-Goker, Bercis, Gencer, Ayse, Ozogul, Ece, Cennet, Omer, Yazici, Gozde, Arica Yegin, Betul, Yabanoglu-Ciftci, Samiye
• Format: Article
• Language: English
• Subjects: Capsule contracture; Chitosan; PLGA-b-PEG nanoparticle; Radiotherapy; TGF-β3
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124715

[Display omitted] •TGF-β3-loaded PLGA-b-PEG nanoparticles showed controlled release profile and high encapsulation efficiency.•Radiotherapy-induced fibrosis reduced by film formulations containing free TGF-β3 or TGF-β3-loaded nanoparticles.•In implant reconstitution, capsular contracture formation was prevented by placing film formulations containing free TGF-β3 or TGF-β3-loaded nanoparticles on the breast implant. Postmastectomy radiotherapy causes capsular contracture due to fibroproliferation of the capsular tissue around the implant. In fibrosis, unlike normal wound healing, structural and functional disorders are observed in the tissues caused by excessive/irregular accumulation of extracellular matrix proteins. It has been reported that transforming growth factor-β3 (TGF-β3) prevents and reverses fibrosis in various tissues or provides scarless healing with its antifibrotic effect. Additionally, TGF-β3 has been shown to reduce fibrosis in radiotherapy-induced fibrosis syndrome. However, no study in the literature investigates the effects of exogenously applied TGF-β3 on capsular contracture in aesthetic or reconstructive breast implant application. TGF-β3, which has a very short half-life, has low bioavailability with parenteral administration. Within the scope of this study, free TGF-β3 was loaded into the nanoparticles to increase its low bioavailability and extend its duration of action by providing controlled release. The aim of this study is to investigate the preventive/improving effects of radiation induced capsular contracture using chitosan film formulations containing TGF-β3 loaded poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles in implant-based breast reconstruction. In the characterization studies of nanoparticles, the particle size and zeta potential of the TGF-β3-loaded PLGA-b-PEG nanoparticle formulation selected to be used in the treatment group were found to be 123.60 ± 2.09 nm and −34.87 ± 1.42 mV, respectively. The encapsulation efficiency of the formulation was calculated as 99.91 %. A controlled release profile was obtained in in vitro release studies. Chitosan film formulations containing free TGF-β3 or TGF-β3-loaded PLGA-b-PEG nanoparticles were used in in vivo studies. In animal studies, rats were randomly distributed into 6 groups (n = 8) as sham, implant, implant + radiotherapy, implant + radiotherapy + chitosan film containing unloaded nanoparticles, implant + radiotherapy + chitosan film co