ABSTRACT
The polymeric nanofiber mats were produced from polylactic acid, methylcellulose, and polyethylene glycol with 5-fluorouracil (5Fu) drug and iron oxide (Fe3O4) nanoparticles. Spectral and crystallographic studies clearly elucidated the ionic interactions, structure and nature of the mats. Fe3O4 nanoparticles <10 nm in size, along with methyl cellulose and polyethylene glycol, have significantly reduced the size of nanofiber mats. The mechanical properties for the mats was found to be challenging; however, surface wettability, swelling capacity, and drug encapsulation efficiency results were promising. A controlled drug release pattern was observed from in vitro drug release study, zero-order kinetics, and a Higuchi model. Nanofiber mats showed higher anticancer activity (78%) against MDA-MB 231 cancer cells, which reveals that a small amount of 5Fu drug (15.86%) with high levels of O2â¢â¢, H2O2, and OH⢠radicals generated from Fe3O4 have catalyzed the Fenton's reaction to eradicate the cancer cells, in a shorter span of 24 h, itself. In addition, the apoptosis assay by dual AO/PI staining method clearly exhibited the apoptotic cancer cells by fluorescence microscopy. Incorporation of Fe3O4 nanoparticles enhanced the anticancer activity of the mats, compared to the commercially available standard 5Fu drug. Nanofiber mats significantly controlled the growth of selected pathogenic microbial strains by the action of the 5Fu drug and Fe3+ ions. The degradation of mats was investigated by an in vitro mass loss study for a period of 360 days. In a nutshell, promising nanofiber mats were produced as targeted drug delivery devices for chemotherapy.
Subject(s)
Antineoplastic Agents , Apoptosis , Breast Neoplasms , Cell Proliferation , Drug Carriers , Drug Screening Assays, Antitumor , Fluorouracil , Nanofibers , Particle Size , Humans , Apoptosis/drug effects , Nanofibers/chemistry , Fluorouracil/pharmacology , Fluorouracil/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Materials Testing , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Line, Tumor , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Drug Liberation , Microbial Sensitivity Tests , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Nanoparticles/chemistryABSTRACT
Nanosized metal oxide-incorporated drug carriers have received significant attention due to their biocompatibility, mechanical strength, controlled drug release, and biodegradability. Herein, an attempt was made to fabricate polycaprolactone-based electrospun nanofiber mats involving the 5-fluorouracil (5Fu) drug, MgO nanoparticle, methyl cellulose, and polyethylene glycol. The chemical interactions, surface wettability, mechanical properties, structural and morphological changes, and thermal stability were studied by the respective analyses. The ionic interaction between 5Fu, MgO, and polymers were found to be responsible for the controlled drug release. Zero-order kinetic and model data also revealed that a controlled drug release pattern was observed in a period of 16 days. Furthermore, the nanofiber mats were subjected to cytotoxicity studies against MDA-MB-231 cancer cell line and the results showed higher cytotoxicity in a short time of 24 h and less toxicity to normal L929 fibroblast cell line. The apoptosis in cancer cell lines was also tested by AO/PI staining assay and confirmed by fluorescence microscopy. In addition, the growth inhibition of several bacterial and fungal strains was tested for the mats and the results exhibited good inhibition activity. Hence, the reported nanofiber drug carrier was found to be an efficient implant for the controlled release of anticancer drug along with other significant properties.