Research On Chloramphenicol Solid Lipid Nanoparticles

Solid lipid nanoparticles(SLN) has attracted increasing attention during recent years, which is the colloidal system for controlled drug delivery with natural or synthetic lipid as drug carrier, such as stearic acid, glycerin monostearate, lecithin. SLN can be used for oral administration, intravenous injection, skin administration, and ophthalmic administration. The main features of SLN are site-specific target, controlled drug release (fast or sustained), high bioavailability, good tolerability, low toxicity and protection of incorporated labile drugs from degradation.The thesis was to investigate chloramphenicol solid lipid nanoparticles (CAP-SLN) for ophthalmic administration. CAP-SLN was prepared by emulsification evaporation-solidification at low temperature technique, loaded with Precirol ATO 5 as lipid material, EPC and F68 as emulsifier. CAP-SLN could produce sustain-release effect and improve the bioavailability of drug.The entrapped efficiency (EE) of CAP-SLN was determined by Ultraviolet absorbance at 278nm after CAP-SLN and free drug were separated on a sephadex-G50 chromatography. The experiment results proved that the methods were accurate, simple and dependable. According to results of the single-factor test, drug-to-lipid ratio, content of F68, emulsifying temperature and emulsion-dispersed phase ratio of volume were the main influence factors. The optimal formulation of CAP-SLN was evaluated by orthogonal design, with the entrapment efficiency and drug loading of CAP-SLN as the criteria. EE of the optimal formulation was 65.9±0.38%, and DL of was 6.59±0.04%.The physicochemical property of CAP-SLN was evaluated. The results indicated CAP-SLN was regular, with the mean diameter of 165.5nm,the Zate potential of -30.5mV, and the pH of 6.31. Results of the preliminary stability experiments showed that the CAP-SLN could be kept stable at 4oC for 30 days. There were no significant changes in the appearance, average size and EE, and the stability of CAP-SLN was good. The formation of CAP-SLN was validated to be different from simple mixture of its components by DSC.In vitro release behavior of chloramphenicol from CAP-SLN in pH 7.4 phosphate buffer at 34oC was investigated in contrast to reference chloramphenicol eye drops. The results showed that initial burst release (52.29% drug released after 4h) was followed by a sustained release (84.06% drug released after 48 h) from CAP-SLN,compared to 86.55 % from burst release of reference in the initial 4h. The drug release profile of CAP-SLN in vitro fitted well to the Weiball distribution.Rabbit ocular irritation experiments were performed, such as single and multiple dosing. There were no significant differences between CAP-SLN and the experiment group on irritation experiments,The results showed CAP-SLN was nonirritant, and the Precirol ATO 5, EPC, F68 of CAP-SLN were biocompatible.Preliminary pharmacokinetics in aqueous humor of rabbits were investigated.The results showed that t_1/2,C_max and AUC of CAP-SLN were 60.773min, 0.617μg/ml and 65.065μg/ml*min,respectively, compared to 34.456min,0.357μg/ml,22.618μg/ml*min of chloramphenicol eye drops. t_1/2,C_max and AUC of CAP-SLN were higher than that of control.thus,CAP-SLN has sustained-release effect and enhance chloramphenicol bioavailability in the aqueous humour.