作者
Rondinelli Donizetti Herculano,Camila Eugênia dos Reis,Silvia Maria Batista de Souza,Giovana Sant’Ana Pegorin Brasil,Mateus Scontri,Satoru Kawakita,Bruna G. Carvalho,Camila Calderan Bebber,Yanjin Su,Ana Paula de Sousa Abreu,Marvin Mecwan,Kalpana Mandal,Ana Marisa Fusco‐Almeida,Maria José Soares Mendes‐Giannini,Nayrim Brizuela Guerra,Cassamo U. Mussagy,Maria Rachel Melo Bosculo,José Lúcio Pádua Gemeinder,Breno Fernando Martins de Almeida,Juliana Ferreira Floriano,Neda Farhadi,Mahsa Monirizad,Danial Khorsandi,Huu Tuan Nguyen,Alejandro Palomar Gómez,Zuzana Tirpáková,Arne Peirsman,J Sasaki,Siqi He,Samuel C. Forster,Betina Sayeg Burd,Mehmet R. Dokmeci,Maíra Terra Garcia,Juliana Campos Junqueira,Ricardo José de Mendonça,Marcos Roberto Cardoso,Lindomar Soares dos Santos,Gláucio Ribeiro Silva,Natan Roberto de Barros,Vadim Jucaud,Bingbing Li
摘要
Amphotericin B (AmB) is the gold standard for antifungal drugs. However, AmB systemic administration is restricted because of its side effects. Here, we report AmB loaded in natural rubber latex (NRL), a sustained delivery system with low toxicity, which stimulates angiogenesis, cell adhesion and accelerates wound healing. Physicochemical characterizations showed that AmB did not bind chemically to the polymeric matrix. Electronic and topographical images showed small crystalline aggregates from AmB crystals on the polymer surface. About 56.6% of AmB was released by the NRL in 120 h. However, 33.6% of this antifungal was delivered in the first 24 h due to the presence of AmB on the polymer surface. The biomaterial's excellent hemo- and cytocompatibility with erythrocytes and human dermal fibroblasts (HDF) confirmed its safety for dermal wound application. Antifungal assay against Candida albicans showed that AmB-NRL presented a dose-dependent behavior with an inhibition halo of 30.0 ± 1.0 mm. Galleria mellonella was employed as an in vivo model for C. albicans infection. Survival rates of 60% were observed following the injection of AmB (0.5 mg.mL−1) in G. mellonella larvae infected by C. albicans. Likewise, AmB-NRL (0.5 mg.mL−1) presented survival rates of 40%, inferring antifungal activity against fungus. Thus, NRL adequately acts as an AmB-sustained release matrix, which is an exciting approach, since this antifungal is toxic at high concentrations. Our findings suggest that AmB-NRL is an efficient, safe, and reasonably priced ($0.15) dressing for the treatment of cutaneous fungal infections.