Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 87, Issue 2, Pages 243-254Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2011.05.025
Keywords
Molecular mechanics; Nano-emulsion characterization; Polymeric nanoparticles; Sustained release; Tuberculosis; Zero-order kinetics
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This study focused on evaluating four emulsion-based processing strategies for polymeric nanoparticle synthesis to explicate the mechanisms of nanoparticle formation and the influence on achieving sustained-release of two anti-tuberculosis drugs, isoniazid and rifampicin. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were formulated with and without sorbitan mono-oleate as a stabilizer using emulsion-solvent-surfactant-evaporation (ESSE) and emulsion-solvent-evaporation (ESE) approaches. An alginate solution gelled by ionic crosslinking with calcium chloride was employed to prepare alginate hydrogel nanoparticles via reverse-emulsion-cationic-gelification (RECG) and reverse-emulsion-surfactant-cationic-gelification (RESCG) approaches. In vitro drug release analysis was performed. The size, zeta potential and morphology of the nanoparticles were analyzed. Molecular mechanics energy relationships (MMER) were employed to explore the spatial disposition of alginate and PLGA with respect to the emulsifying profile of sorbitan rnonooleate and to corroborate the experimental findings. Results revealed that particle size of the PLGA nanoparticles was influenced by the stabilizer concentration. Nanoparticles synthesized by the ESSE approach had smaller sizes of 240 +/- 8.7 nm and 195.5 +/- 5.4 nm for rifampicin- and isoniazid-loaded nanoparticles, respectively. This was a substantial size reduction from nanoparticles generated by the ESE approach (> 1000 nm). The RESCG approach produced stable and higher nanoparticle yields with desirable size (277 +/- 1.0 nm; 289 +/- 1.2 nm), a low polydispersity index (27.1 +/- 0.3 mV; 28.5 +/- 0.5 mV) and drug entrapment efficiency of 73% and 75% for isoniazid and rifampicin, respectively. Drug release from the ESSE and RESCG synthesized nanoparticles displayed desirable release of the two anti-TB drugs with sustained zero-order kinetics over a period of 8 h. MMER supported the mechanisms of nanoparticle formation with a sphericalized interlaced network configuration. (C) 2011 Elsevier B.V. All rights reserved.
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