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Journal of Drug Delivery
Volume 2012 (2012), Article ID 579629, 18 pages
http://dx.doi.org/10.1155/2012/579629
Research Article

Composite Polylactic-Methacrylic Acid Copolymer Nanoparticles for the Delivery of Methotrexate

1Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
2Department of Neurology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
3Department of Neurosurgery, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
4Department of Medicinal Chemistry, College of Pharmacy, Qassim University, Buraidah, Al-Qassim 51452, Saudi Arabia
5School of Pharmacy and Pharmaceutical Sciences, St. John’s University of Tanzania, Dodoma, Tanzania
6School of Chemical and Metallurgical Engineering, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg 2050, South Africa

Received 6 March 2012; Accepted 10 May 2012

Academic Editor: R. Pignatello

Copyright © 2012 Bongani Sibeko et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The purpose of this study was to develop poly(lactic acid)-methacrylic acid copolymeric nanoparticles with the potential to serve as nanocarrier systems for methotrexate (MTX) used in the chemotherapy of primary central nervous system lymphoma (PCNSL). Nanoparticles were prepared by a double emulsion solvent evaporation technique employing a 3-Factor Box-Behnken experimental design strategy. Analysis of particle size, absolute zeta potential, polydispersity (Pdl), morphology, drug-loading capacity (DLC), structural transitions through FTIR spectroscopy, and drug release kinetics was undertaken. Molecular modelling elucidated the mechanisms of the experimental findings. Nanoparticles with particle sizes ranging from 211.0 to 378.3 nm and a recovery range of 36.8–86.2 mg (Pdl0.5) were synthesized. DLC values were initially low (12±0.5%) but were finally optimized to 98±0.3%. FTIR studies elucidated the comixing of MTX within the nanoparticles. An initial burst release (50% of MTX released in 24 hours) was obtained which was followed by a prolonged release phase of MTX over 84 hours. SEM images revealed near-spherical nanoparticles, while TEM micrographs revealed the presence of MTX within the nanoparticles. Stable nanoparticles were formed as corroborated by the chemometric modelling studies undertaken.