Poly (D,L-lactic-co-glycolide) Nanoparticles for the Improved Therapeutic Efficacy of All-trans-retinoic Acid: A Study of Acute Myeloid Leukemia (AML) Cell Differentiation In Vitro

Aswathy      Mary Simon; Sankar      Jagadeeshan; Emimol      Abraham; Ashalatha      Akhilandeshwaran; Jisha      J. Pillai; Nisha      Asok Kumar; Asha      Nair Sivakumari; Gopalakrishnapillai      Sankaramangalam Vinod Kumar

Abstract

All-trans-retinoic acid reverses malignant cell growth and induces cell differentiation and apoptosis. Poor aqueous solubility and uncertain bioavailability are the limiting factors for using all-trans-retinoic acid for tumor therapy. The objective of present study was to encapsulate the hydrophobic drug all-trans-retinoic acid in the polymer poly (lactide-coglycolide). The encapsulation was expected to improve the bioavailability and solubility of the drug. Oil in water single emulsion solvent evaporation technique used for the preparation efficiently encapsulated about 60% of the drug. The drug release profile showed a biphasic pattern with 70% of the drug being released in first 48 hrs and the residual drug showing a slow controlled release reaching up to 8 days. The particle size of 150-200 nm as determined with TEM was ideal for tumor targeting. All-trans-retinoic acid loaded nanoparticles were efficient to induce differentiation and blocked the proliferation of HL-60 cells invitro. These studies also revealed that the dosage of drug required for the therapeutic effects have been reduced efficiently. Our studies thereby demonstrate that Poly (lactide-co-glycolide) based nanoparticles may be efficient for parenteral administration of the drug.

Keywords: All-trans-retinoic acid, Controlled release, Nanoparticles, cancer, Myeloid leukemia, HL-60, lactide-co-glycolide, vitamin A, cell, cytochrome P450