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.

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.

• Authors: Aswathy Mary Simon, Sankar Jagadeeshan, Emimol Abraham, Ashalatha Akhilandeshwaran, Jisha J Pillai, Nisha Asok Kumar, Asha Nair Sivakumari, Gopalakrishnapillai Sankaramangalam Vinod Kumar
• Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) (Med Chem) Vol. 8 Issue 5 Pg. 805-10 (Sep 2012) ISSN: 1875-6638 [Electronic] Netherlands
• PMID: 22741806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Emulsions
• Polyglactin 910
• Tretinoin

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Differentiation
• Drug Carriers (chemical synthesis, chemistry)
• Drug Compounding
• Emulsions
• HL-60 Cells (drug effects)
• Humans
• Hydrophobic and Hydrophilic Interactions
• Kinetics
• Leukemia, Myeloid, Acute (drug therapy, pathology)
• Microscopy, Electron, Transmission
• Nanoparticles (chemistry)
• Particle Size
• Polyglactin 910 (chemistry)
• Solubility
• Tretinoin (chemistry, pharmacology)