Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design

• Published in: International journal of nanomedicine 2011-01, Vol.6 (default), p.683-692
• Main Authors: Hao, Jifu, Fang, Xinsheng, Zhou, Yanfang, Wang, Jianzhu, Guo, Fengguang, Li, Fei, Peng, Xinsheng
• Format: Article
• Language: English
• Subjects: Administration, Topical; Analysis of Variance; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacokinetics; Box-Behnken design; chloramphenicol; Chloramphenicol - administration & dosage; Chloramphenicol - chemistry; Chloramphenicol - pharmacokinetics; Computer-Aided Design; Drug Delivery Systems - methods; Glycerides - chemistry; melt-emulsion ultrasonication and low temperature-solidification technique; Microscopy, Electron, Scanning; Models, Chemical; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Nephelometry and Turbidimetry; Ophthalmic Solutions - chemistry; Ophthalmic Solutions - pharmacokinetics; Original Research; Particle Size; Poloxamer - chemistry; Reproducibility of Results; solid lipid nanoparticle; Surface Properties
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S17386

The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X(1)), surfactant (X(2)), and drug/lipid ratio (X(3)) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was -8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas-Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release.