Preparação e caracterização de nanofibras magnéticas para liberação controlada de fármacos e hipertemia

Abstract

In the present work, magnetic nanofibers containing nanohydroxyapatite (nHAm) were obtained for the release of antineoplastic agent mitomycin C (MCC) using PLGA and PLGA modified with sulfamethoxazole (PLGA-S) as polymer matrix. This work deals the synthesis of n-HAm and the functionalization of PLGA with sulfamethoxazole (SMZ) and the preparation of nanofibers by the electrospun technique. Physical-chemical characterization and cytotoxicity tests were made for all materials in normal cells (osteoblast and fibroblast) and tumorcells (osteosarcoma and mammary carcinoma). The n-HAm were synthesized by co-precipitation method. The physicalchemical and morphological results showed that n-HAm exhibited a rod shape,size of 94x14 nm, high magnetization of saturation, superparamagneticbehavior and composed by a mixture of magnetite, maghemite, iron oxidehydroxide and iron phosphate. The functionalization of PLGA with SMZ was effectively performed and characterized by FTIR and NMR, obtaining 3 % of functionalization. The nanofibers were prepared with 30 % of n-HAm incorporated within the polymeric matrix, promoting a fast heating through the application of an alternating magnetic field and releasing the MCC up to 30 days. Cytotoxicity assays showed that PLGA/MMC and PLGA/HAm/MCC nanofibers display high cytotoxicity on tumor cells. The PLGA modified with SMZ nanofibers, PLGA-S/MCC and PLGA-S/Ham, also showed remarkable cytotoxicity against tumor cells. In addition, preliminary tests in mice with subcutaneous implant of PLGA/HAm/MCC nanofibers showed significant tumor suppression in comparison to the untreated group by hyperthermia, suggestingthat hyperthermic treatment may increase the cytotoxic effect of this material.