| Polymeric micelles based on amphiphilic scorpion-like macromolecules (AScMs) were prepared by organic solvent/water (O/W) emulsion technique, and evaluated as novel drug delivery vehicle for indomethacin (IMC). Two AScMs block copolymers were investigated for IMC incorporation, M12P 5 and M12P2, respectively. For both AScMs studied, a considerable effect of feed drug:polymer ratio and molecular weight of hydrophilic segment of block copolymer on drug loading content and entrapment efficiency were observed. The sizes of IMC-loaded M12P5 and M 12P2 polymeric micelles were < 20 nm with narrow size distribution. In vitro release studies showed that compared to IMC alone, IMC release from M12P5 and M12P 5 polymeric micelles showed sustained release character during 24 h of experiment (p<0.05). In vitro cytotoxicity studies, confirmed that M12P5 and M12P2 polymeric micelles did not induce any remarkable cytotoxicity against HUVEC cells up to concentration of 1 and 0.5 mM, respectively. Overall, the results of our investigation show that water-insoluble drug (e.g. indomethacin) was successfully incorporated into the M12P5 and M 12P2 polymeric micelles by optimizing incorporation conditions. However, between two AScMs studied, M12P5 has better potential as a novel drug delivery system for different hydrophobic drugs.; To better understand the fate of polymeric micelles (e.g. amphiphilic scorpion-like macromolecules, AScMs) and unimolecular micelles (e.g., amphiphilic star-like macromolecules, ASMs) in HUVECs, their internalization and intracellular trafficking were investigated. Uptake studies in the presence of metabolic inhibitors revealed that AScMs and ASMs micelles were internalized by non-specific receptor mediated endocytosis as well as fluid phase endocytosis. However, spontaneous non-energy driven processes such as membrane fusion or insertion into cellular membrane may also play a role in the polymer uptake. To examine the intracellular fate of AScMs in HUVECs, polymeric micelles (e.g., M 12P5) were labeled with fluorescein isothiocyanate (FITC). TEM and confocal microscopy studies revealed that following uptake, micelles were localized into cytoplasm as well as the nucleus. In summary, our findings suggest that AScM-based micelle are rapidly internalized into HUVECs; following internalization the AScMs micelles are localized into cytoplasm as well as nucleus. Therefore, AScMs are promising candidate for intracytoplasmic delivery of drugs, proteins and/or genes. |
