RESUMO
This study explored the potential of poly-(lactic-co-glycolic) acid (PLGA) nanoparticles to enhance the effectiveness of anticancer treatments through combination therapy with phytol and α-bisabolol. The encapsulation efficiency of the nanoparticles was investigated, highlighting the role of ionic interactions between the drugs and the polymer. Characterization of PLGA-Phy+Bis nanoparticles was carried out using DLS with zeta potential and HR-TEM for size determination. Spectrophotometric measurements evaluated the encapsulation efficiency, loading efficiency, and in vitro drug release. FTIR analysis assessed the chemical interactions between PLGA and the drug actives, ensuring nanoparticle stability. GC-MS was employed to analyze the chemical composition of drug-loaded PLGA nanocarriers. Cytotoxicity was evaluated via the MTT assay, while Annexin V-FITC/PI staining and western blot analysis confirmed apoptotic cell death. Additionally, toxicity tests were performed on L-132 cells and in vivo zebrafish embryos. The study demonstrates high encapsulation efficiency of PLGA-Phy+Bis nanoparticles, which exhibit monodispersity and sizes of 189.3±5nm (DLS) and 268±54 nm (HR-TEM). Spectrophotometric analysis confirmed efficient drug encapsulation and release control. FTIR analysis revealed nanoparticle structural stability without chemical interactions. MTT assay results demonstrated the promising anticancer potential of all the three nanoparticle types (PLGA-Phy, PLGA-Bis, and PLGA-Phy+Bis) against lung cancer cells. Apoptosis was confirmed through Annexin V-FITC/PI staining and western blot analysis, which also revealed changes in Bax and Bcl-2 protein expression. Furthermore, the nanoparticles exhibited non-toxicity in L-132 cells and zebrafish embryo toxicity tests. PLGA-Phy+Bis nanoparticles exhibited efficient encapsulation, controlled release, and low toxicity. Apoptosis induction in A549 cells and non-toxicity in healthy cells highlight their clinical potential.
Assuntos
Apoptose , Sinergismo Farmacológico , Neoplasias Pulmonares , Sesquiterpenos Monocíclicos , Nanopartículas , Fitol , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Peixe-Zebra , Apoptose/efeitos dos fármacos , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Nanopartículas/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Monocíclicos/administração & dosagem , Fitol/administração & dosagem , Fitol/farmacologia , Fitol/química , Fitol/toxicidade , Linhagem Celular Tumoral , Portadores de Fármacos/química , Células A549 , Liberação Controlada de Fármacos , Sesquiterpenos/farmacologia , Sesquiterpenos/administração & dosagem , Sesquiterpenos/química , Sesquiterpenos/toxicidade , Sobrevivência Celular/efeitos dos fármacosRESUMO
The present study was aimed to evaluate the antioxidant and anticancer potential of fucoidan isolated from Sargassum polycystum. The isolated fucoidan was successfully purified by DEAE cellulose-ion exchange chromatography and dialysis. Totally four active fractions (F1-F4) were collected and explored its chemical constitution by calorimetric assays. Among them, fraction 2 (F2) showed the higher yield percentage, fucose and sulphate content. Further, monosaccharide composition, structural and functional properties of the F2 was analyzed by HPLC, FTIR and NMR. F2 shows highest DPPH radical scavenging activity (55.94⯱â¯0.69%), reducing power (0.33 absorbance rate), hydrogen peroxide scavenging activity (71.76⯱â¯2.14%) and nitric oxide radical scavenging activity (51.81⯱â¯1.04%) at 1000⯵g/ml. The cell viability of MCF-7 and HCT-15 cell lines was proportionate to the concentration of F2 with an estimated IC50 was 20 and 50⯵g/ml respectively. The fluorescence and confocal laser scanning microscopic analysis demonstrated the apoptotic morphological changes and cell mediated death in F2 treated cancer cells. Higher amount of LDH release was found in the F2 treated cancer cells than the control group. Thus, the present finding proved that the isolated F2 encompasses significant antioxidant and anticancer property.