Preparation And Lymphatic Transport Of Solid Lipid Nanoparticles

Solid lipid nanoparticles (SLN) are colloidal carrier system for controlled drug delivery and followed by the development of emulsion, liposomes, microparticles and nanoparticles based on synthetic polymers. They combine advantages of emulsions, liposomes and polymeric nanoparticles. Identical to polymeric nanoparticles, their solid matrix protects incorporated active ingredients against chemical degradation and provides the highest flexibilities in the modulation of the drug release profiles. Similar to emulsions and liposomes, they are composed of well physiologically tolerated excipients and can be produced on large industrial scale by high pressure homogenization.The present study prepared several stable SLN using different kinds of lipids. Monostearin SLN were prepared by solvent diffusion method in aqueous system. The lipophilic model drug clobetasol propionate was incorporated to study the recovery of nanoparticles, entrapment efficacy, zeta potential (charge) and drug delivery characterization. Differential scanning calorimetry (DSC) was used to determine the status of clobetasol propionate in SLN. Stearic acid SLN were prepared by the same solvent diffusion technique and the optimal cryoprotectant was selected by freeze-thaw test and reconstitution of the lyophilized products. Covalent conjugation with fluorescein isothiocyanate (FITC) yielded labeled octadecylamine molecules, which was investigated by DSC and infraredspectroscopy (IR) measure. The compound was successfully formulated into nanoparticles by solvent diffusion method, incorporated to the model drug of Cyclosporin A (CyA). The recovery of nanoparticles, entrapment efficacy, zeta potential (charge) and drug delivery characterization were studied. Using pulmonary epithelium cell A549 as model cell, the interaction of FITC labeled ODA nanoparticles (ODA-SLN) and A549 cell was investigated. Viability determinations of ODA-SLN were performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyl-tetrazolium bromide (MTT) assay. The relative bioavailability of the CyA loaded ODA-SLN given by gavage was studied with a commercially available CyA solution product as a reference formulation. To study the intestinal lymphatic transport, thoracic duct -cannulated rats were studied. The lymph was directed externally by cannulating the thoracic duct and blood was withdrawn from the caudal vein.Monostearin solid lipid nanoparticles were quickly prepared by a novel solvent diffusion method in aqueous system. The particles prepared under the acidic condition exhibited bimodal particle size distribution, with a number mean diameter of 116.2nm (92.7%) and 418.4 nm (7.3%), respectively. And the volume mean diameter is 143.3nm (20.0%) and 432.4nm (80.0%), respectively. SLN could be separated completely by centrifuge of 4000 r-min-1 at the condition of the acidic dispersed aqueous medium with pH 1.10. At this time, the zeta potential value of drug loaded SLN is approached zero and forming aggregation of SLN. The recovery of nanoparticles was markedly increased compared to using a usual aqueous at pH 5.73. As DSC measurement with powdered SLN, we found that the endothermic peak presented at the same temperature point as the original drug crystal. It means that the original drug crystal lattice is forming after preparation. After burst drug release at the first 3 h, a distinctly prolonged release over a monitored period of 4days was observed and nearly 6.0% drug was released in each day. These findings indicated that the internal structure of the SLN was a polymeric lipid matrix. As some drug adsorbed on the surface of nanoparticles, the dissolution profile of the SLN exhibited a burst of drug during initial stage. During the later stage, the drug release rate was determined by the diffusion of drug from the rigid matrix structure.The stearic acid SLN prepared by solvent diffusion method were monodispersed spheres. The number mean diameter and the volume mean diameter were 166.8 nm and 231.2 nm, respectively. Poloxamer 188 with different concentration of 2.5%...