[en] In the present work, magnetic nanofibers containing nanohydroxyapatite (n-HAm) 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 tumor cells (osteosarcoma and mammary carcinoma). The n-HAm were synthesized by co-precipitation method. The physical-chemical and morphological results showed that n-HAm exhibited a rod shape, size of 94x14 nm, high magnetization of saturation, superparamagnetic behavior and composed by a mixture of magnetite, maghemite, iron oxide-hydroxide 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, suggesting that hyperthermic treatment may increase the cytotoxic effect of this material. (author)

[en] Highlights: • Nanofibers delivered OTC and ZnO, antibacterial agents against periodontal disease. • PCL nanofibers exhibited a sustained OTC release for up to 5 days. • Nanofibers were not cytotoxic on fibroblastic cells. • Nanofibers exhibited good antimicrobial activity against mixed bacterial culture. -- Abstract: Periodontal diseases (PD) are mixed bacterial infections caused by microorganisms that colonize the tooth surface, leading to destructions at tooth-supporting tissues. Several local delivery systems, as nanofibers, have been developed for the treatment of PD. The purpose of the present study was developing polycaprolactone (PCL) nanofibers incorporating two antibacterial agents, OTC and ZnO, for use in the treatment of PD. Nanofibers were produced by electrospinning method: PCL loaded with ZnO (PCL-Z), PCL loaded with OTC (PCL-OTC), PCL loaded with OTC and ZnO (PCL-OTCz) and pristine PCL (PCL-P). The nanofibers were characterized physicochemically using different techniques. In addition, in vitro study of the OTC release from the nanofibers was performed. The PCL-OCT showed sustained release of the drug up to 10 h, releasing 100% of OTC. However, the PCL-OTCz nanofiber showed a slow release of OTC up to 120 h (5th day) with 54% of drug retention. The cytotoxicity assay showed that PCL-OTC nanofiber was slightly cytotoxic after 48 h and the other nanofibers were non-cytotoxic. The antibacterial activity of the nanofibers was evaluated by qualitative and quantitative analysis and against mixed bacterial culture, composed of four Gram-negative anaerobic bacteria involved in periodontal diseases. The disk diffusion method showed that the PCL-OTC displayed higher inhibition zone than PCL-OTCz (p < 0.001). The quantitative analysis, evaluated by broth culture, showed that the PCL-OTC and PCL-OTCz exhibited excellent activity against a mixed bacterial culture with growth inhibition of 98.0% and 97.5%, respectively. Based on these results, the PCL-OTCz nanofibers developed have great potential as a drug delivery system for the PD treatment.