Topotecan-tamoxifen duple PLGA polymeric nanoparticles: investigation of in vitro, in vivo and cellular uptake potential.

Abstract

The dual drug loaded poly(dl-lactic-co-glycolic acid) (PLGA(1)) nanoparticles (TOP-TAM NPs(2)) concurrently delivering topotecan hydrochloride (TOP(3)) and tamoxifen citrate (TAM(4)) were developed to achieve synergism for the treatment of breast cancer by enhancing the permeation of TOP through the gut and the cells present in the breast. TAM acted as P-glycoprotein (P-gp(5)) inhibitor, reduced the side effects of individual drugs by reducing the dose. The NPs were prepared by double emulsion (w/o/w) method. The optimized TOP-TAM NPs were found to have smooth and spherical morphology by using SEM(6) and TEM(7) technique. Similarly size of nanoparticles was found to be 151.2 ± 1.6 nm with 0.147 ± 0.03 polydispersity index (PDI(8)). The percentage entrapment efficiency of 95.17 ± 3.57 and 57.77 ± 2.2 was found for TAM and TOP respectively. The lyophillized nanoparticles under DSC(9) showed amorphous nature of both TOP and TAM. In an in vitro release study the release of drugs from TOP-TAM NPs was found to follow the Higuchi pattern. The ex vivo gut permeation study revealed that the TAM enhanced the permeation of TOP and increased its bioavailability by 1.9 folds. The permeation and activity of combination of drugs were further confirmed by carrying out cell line studies on MCF-7 cells.

• Authors: Tahir Khuroo, Devina Verma, Sushama Talegaonkar, Santwana Padhi, Amulya K Panda, Zeenat Iqbal
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 473 Issue 1-2 Pg. 384-94 (Oct 01 2014) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 25051112 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Hormonal
• Drug Carriers
• Topoisomerase I Inhibitors
• Tamoxifen
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Topotecan

Topics

• Animals
• Antineoplastic Agents, Hormonal (administration & dosage, chemistry)
• Biological Transport
• Drug Carriers (administration & dosage, chemistry)
• Female
• Humans
• Intestinal Absorption
• Lactic Acid (administration & dosage, chemistry)
• MCF-7 Cells
• Nanoparticles (administration & dosage, chemistry)
• Polyglycolic Acid (administration & dosage, chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Rats, Wistar
• Tamoxifen (administration & dosage, chemistry)
• Topoisomerase I Inhibitors (administration & dosage, chemistry)
• Topotecan (administration & dosage, chemistry)