RESUMEN
Hybrid composite nanofibers, with the potential to enhance cell adhesion while improving sustained drug release profiles, were fabricated by the blend electrospinning of poly(d,l-lactic-co-glycolic acid) (PLGA), gelatin, pluronic F127 and prodigiosin (PG). Scanning Electron Microscopy (SEM) images of the nanofibers revealed diameters of 1.031⯱â¯0.851⯵m and 1.349⯱â¯1.264⯵m, corresponding to PLGA/Ge-PG and PLGA/Ge-F127/Ge, respectively. The Young's moduli were also determined to be 1.446⯱â¯0.496â¯kPa and 1.290⯱â¯0.617â¯kPa, while the ultimate tensile strengths were 0.440⯱â¯0.117â¯kPa and 0.185⯱â¯0.480â¯kPa for PLGA/Ge-PG and PLGA/Ge-F127/Ge, respectively. In-vitro drug release profiles showed initial (burst) release for a period of 1â¯h to be 26.000⯱â¯0.004% and 16.000⯱â¯0.015% for PLGA/Ge and PLGA/Ge-F127 nanofibers, respectively. This was followed by 12â¯h of sustained release, and subsequent slow sustained release of PG from the composite nanofibers. The cumulative release of PG (for three days) was determined to be 82.0⯱â¯0.1% for PLGA/Ge and 49.7⯱â¯0.1% for PLGA/Ge-F127 nanofibers. The release exponents (n) show that both nanofibers exhibit diffusion-controlled release by non-Fickian (zeroth order) and quasi-Fickian diffusion in the initial and sustained release regimes, respectively. The suitability of the composite nanofibers for supporting cell proliferation and viability, as well as improving sustained release of the drug were explored. The in-vitro effects of cancer drug (PG) release were also studied on breast cancer cell lines (MCF-7 and MDA-MB-231 cells). The implications of the results are discussed for the potential applications of drug-nanofiber scaffolds as capsules for localized delivery of chemotherapeutic drugs for the treatment of triple negative breast cancer.
Asunto(s)
Nanofibras , Neoplasias de la Mama Triple Negativas , Humanos , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , ProdigiosinaRESUMEN
This paper presents the anomalous release kinetics of a cancer drug (prodigiosin) frompoly-n-isopropyl-acrylamide (P(NIPA))-based gels. The release exponents, n, which correspond to the drug release mechanisms, were found to be between 0.41 and 1.40. This is within a range that include Fickian case I (n = 0.45) and non-Fickian diffusion (case II) (n > 0.45) for cylindrical drug-loaded structures. The results, however, suggest that the release exponents, n, correspond mostly to anomalous case II and super case II transport mechanics with sigmoidal characteristics. The drug release kinetics of the P(NIPA)-based hydrogels are well described by bi-dose functions. The observed drug release behavour is related to the porosity of the hydrogels, which can be controlled by cross-linking and copolymerization with acrylamide, which also improves the hydrophilicity of the gels. The paper also presents the effects of cancer drug release on cell survival (%), as well as the cell metabolic activities of treated cells and non-treated cells. The implications of the results are discussed for the development of implantable thermosensitive gels for the controlled release of drugs for localized cancer treatment.