1, 2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamin (DPPE), doxorubicin and folic acid conjugated micelles for cancer management in tumor bearing BALB/c mice.

Pravin S Uttekar, Vishal D Yadav, Durgacharan A Bhagwat

Bioorganic & medicinal chemistry letters 2021 Oct 15

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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. Copyright © 2021 Elsevier Ltd. All rights reserved.

Citation

Pravin S Uttekar, Vishal D Yadav, Durgacharan A Bhagwat. 1, 2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamin (DPPE), doxorubicin and folic acid conjugated micelles for cancer management in tumor bearing BALB/c mice. Bioorganic & medicinal chemistry letters. 2021 Oct 15;50:128337