Solid Lipid Nanoparticles Matrix Research Articles

Preparation and characterization of solid lipid nanoparticles containing peptide

Solid lipid nanoparticles (SLN) are an alternative colloidal carrier system for controlled drug delivery. However, only a few have been studied regarding the incorporation of peptides into SLN, due to the hydrophilic peptide not easy to enter the lipophilic matrix of SLN. In the present report, peptide-loaded solid lipid nanoparticles were prepared by a novel solvent diffusion method in an aqueous system. The model peptide gonadorelin was incorporated to study the entrapment efficiency, size, zeta potential (charge) and drug delivery characterization. Gonadorelin and monostearin were dissolved in acetone and ethanol at 50 °C in water bath, the resultant organic solution was poured into an aqueous containing 1% polyvinyl alcohol (PVA) under mechanical agitation. The peptide-loaded solid lipid nanoparticles were quickly produced and separated by centrifugation. The average volume diameter of gonadorelin-loaded SLN is 421.7 nm and the zeta potential of SLN is −21.1 mV dispersed in distilled water. Up to 69.4% of gonadorelin can be incorporated. In vitro release of gonadorelin from SLN is slow. In the test solution of a 0.1N hydrochloric acid for 2 h and then transferred in a pH 6.8 phosphate buffer (simulative gastrointestinal fluid), the drug-release behavior from SLN suspension exhibited a biphasic pattern. After burst drug-release at the first 6 h at a percentage of 24.4% of loaded gonadorelin, a distinctly prolonged release over a monitored period of 12 days was observed and nearly 3.81% of drug was released in each day. In the test solution of a pH 6.8 phosphate buffer (simulative intestinal fluid), the drug-release rate from SLN was similar to that in the simulative gastrointestinal fluid. Further, a novel preparation method in the present research for peptide-loaded SLN was established. These results also demonstrate the principle suitability of SLN as a prolonged release formulation for hydrophilic peptide drugs.

Effect of lipid matrix and size of solid lipid nanoparticles (SLN) on the viability and cytokine production of macrophages

Solid lipid nanoparticles (SLN) interact with mononuclear cells following intravenous injection. Little is known about the interaction of SLN with these cells, including cytotoxic effects and a possible up-regulation of pro-inflammatory cytokines. Therefore, we investigated the influence of lipid matrix, concentration, and size of SLN on murine peritoneal macrophages (mφ). mφ were incubated with SLN consisting of different lipid matrices and coated with the same surfactant. Cytotoxicity as assessed by MTT test was found to be concentration-dependent and was dramatically influenced by the lipid matrix. Marked cytotoxic effects were observed when cells were incubated with SLN consisting of stearic acid (STE) or dimethyl-dioctadecylammonium bromide (DDA) at concentrations of 0.01%, whereas SLN consisting of triglycerides, cetylpalmitate or paraffin did not exert major cytotoxic effects at the same concentrations. Cytotoxic effects were most likely caused by products of enzymatic degradation including free stearic acid. Analysis of cytokine production by mφ following incubation with SLN revealed concentration-dependent decreases in IL-6 production. These decreases seemed to be associated with cytotoxic effects. IL-12 and TNF-α production was neither detected in supernatants of mφ treated with SLN at any concentration nor in those of untreated cells. The size of SLN did neither affect cytotoxicity of SLN nor resulted in induction or digression of cytokine production by mφ. In conclusion, results of the present study revealed that the nature of the lipid matrix and the concentration of SLN dramatically impact cytotoxicity of SLN on mononuclear cells. Lipid matrices of SLN should therefore be carefully chosen and tested for later intravenous use.