Aim of the present investigation was to assess and compare the in-vitro and in-vivo cancer targeting propensity of DPPE–FA–DOX Micelles and free DOX in tumor bearing BALB/c mice. The DOX was conjugated with 1, 2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamin (DPPE) and folic acid using Di-cyclohexyl-carbodiimide, confirmed by Fourier transform infrared spectroscopy (FTIR) and proton NMR. DPPE–FA–DOX micelles were prepared using thin film method and evaluated for zeta potential, particle size, surface morphology, in- vitro drug release study etc. In-vitro anticancer activity and apoptosis assay was evaluated in breast cancer (MCF-7) cells using MTT assay and flow cytometer respectively. In-vivo biodistribution and toxicity assessment were evaluated in rats whereas antitumor activity in tumor bearing BALB/c mice. Prepared micelles were spherical with size and zeta potential of 295.6 + 84.4 nm and 0.8 ± 0.24 mV respectively. Apoptosis assay for DPPE–FA–DOX micelles treated cells using Annexin V/PI staining demonstrated 56.2% apoptotic cells. Remarkably, DPPE–FA–DOX micelles improved DOX bioavailability by 7 fold and diminished plasma elimination with no sign of tissue toxicity compared to free DOX. In-vivo biodistribution studies revealed that micelles facilitated higher accumulation of DOX in tumor than free DOX. DPPE–FA–DOX micelles treated mice survived for 62 days than Free DOX (40 days), revealed by Kaplan-Meier survival curve analysis. Histopathological examination of liver, kidney and heart tissues of micelles treated rat’s corroborated reduced systemic toxicity than free DOX. Conclusively, DPPE–FA–DOX micelles could potentially facilitate the targeted delivery of DOX to tumors.

本研究的目的是评估和比较DPPE-FA-DOX 胶束和游离 DOX 在荷瘤 BALB/c 小鼠中的体外和体内癌症靶向倾向。DOX 与 1, 2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamin (DPPE) 和使用二环己基碳二亚胺的叶酸结合，通过傅里叶变换红外光谱 (FTIR) 和质子 NMR 证实。使用薄膜法制备 DPPE-FA-DOX 胶束并评估 zeta 电位、粒径、表面形态、体外药物释放研究等。在乳腺癌 (MCF-7) 中评估体外抗癌活性和细胞凋亡测定) 细胞分别使用 MTT 法和流式细胞仪。体内在大鼠中评估生物分布和毒性评估，而在荷瘤 BALB/c 小鼠中评估抗肿瘤活性。制备的胶束呈球形，大小和 zeta 电位分别为 295.6 + 84.4 nm 和 0.8 ± 0.24 mV。使用膜联蛋白 V/PI 染色对 DPPE-FA-DOX 胶束处理的细胞进行的细胞凋亡测定显示 56.2% 的细胞凋亡。值得注意的是，与游离 DOX 相比，DPPE-FA-DOX 胶束将 DOX 的生物利用度提高了 7 倍，并减少了血浆消除，没有任何组织毒性迹象。体内生物分布研究表明，胶束促进 DOX 在肿瘤中的积累高于游离 DOX。Kaplan-Meier 生存曲线分析显示，DPPE-FA-DOX 胶束处理的小鼠比游离 DOX（40 天）存活了 62 天。胶束处理的大鼠肝脏、肾脏和心脏组织的组织病理学检查证实，其全身毒性比游离 DOX 低。总之，DPPE-FA-DOX 胶束可能有助于将 DOX 靶向递送至肿瘤。