Solid lipid nanoparticles optimized by 22 factorial design for skin administration: Cytotoxicity in NIH3T3 fibroblasts.

The present study focuses on the characterization of the cytotoxic profile on NIH3T3 mouse embryonic fibroblasts of solid lipid nanoparticles (SLN) optimized by a 22 full factorial design for skin administration. To build up the surface response charts, a design of experiments (DoE) based on 2 independent variables was used to obtain an optimized formulation. The effect of the composition of lipid and water phases on the mean particle size (z-AVE), polydispersity index (PdI) and zeta potential (ZP) was studied. The developed formulations were composed of 5.0% of lipid phase (stearic acid (SA), behenic alcohol (BA) or a blend of SA:BA (1:1)) and 4.7% of surfactants (soybean phosphatidylcholine and poloxamer 407). In vitro cytotoxicity using NIH3T3 fibroblasts was performed by MTT reduction assay. This factorial design study has proven to be a useful tool in optimizing SLN (z-AVE ∼ 200 nm), which were shown to be non-cytotoxic. The present results highlight the benefit of applying statistical designs in the preparation and optimization of SLN formulations.

Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria.

Levofloxacin is a synthetic broad-spectrum antibacterial agent for oral or intravenous administration. Chemically, levofloxacin is the levorotatory isomer (L-isomer) of racemate ofloxacin, a fluoroquinolone antibacterial agent. Quinolone derivatives rapidly and specifically inhibit the synthesis of bacterial DNA. Levofloxacin has in vitro activity against a broad range of aerobic and anaerobic Gram-positive and Gram-negative bacteria. However, formulation of combined poloxamers thermoregulated (as Pluronic® F127) and levofloxacin for use in multiresistant bacterial treatment were poorly described in the current literature. Thus, the aim of the present work is to characterize poloxamers for levofloxacin controlled release and their use in the treatment of multidrug bacterial resistance. Micelles were produced in colloidal dispersions, with a diameter between 5 and 100 nm, which form spontaneously from amphiphilic molecules under certain conditions as concentration and temperature. Encapsulation of levofloxacin into nanospheres showed efficiency and enhancement of antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae when compared with only levofloxacin. Furthermore, all formulations were not cytotoxic for NIH/3T3 cell lineage. In conclusion, poloxamers combined with levofloxacin have shown promising results, better than alone, decreasing the minimal inhibitory concentration of the studied bacterial multiresistance strains. In the future, this new formulation will be used after being tested in animal models in patients with resistant bacterial strains.