Effect of solid lipid nanoparticles and chitosan nanoparticles formulation on physicochemical properties and ability for transdermal delivery of HIV plasmid DNA vaccine

Abstract

Effect of solid lipid nanoparticles (SLN) and chitosan nanoparticles (CSN) formulation composition on their physicochemical properties and ability for transdermal delivery of HIV plasmid DNA (pDNA) vaccine were determined. The SLN formulated according to the face-centered central composite design with varying in concentration of mixture of Tween 80 and Span 85, dimethyldioctadecyl ammonium bromide and cholesterol had particle size of 136-191 nm with polydispersity index (PI) 0.23-0.37 and zeta potential 11-61 mV and were in solid state at room temperature. The model equations of responses fitted well with quadratic equations. The CSN prepared at varying ratios of chitosan:tripolyphosphate had particle size of 258-997 nm, PI 0.28-0.54 and zeta potential 10-39 mV. SLN were quite stable for 2 months while the changes of CSN were found within 1 month. The ability of nanoparticles to form complex with pDNA was affected by formulation compositions. It was found that the CSN could retain pDNA under electrical field at the lowest nanoparticles:pDNA ratio. In vitro cytotoxicity results demonstrated that HeLa cells were not well tolerant by high concentrations of SLN but could survive in CSN. The results of in vitro HIV pDNA vaccine transfection and mice immunization showed ability of SLN and CSN to use as a vector for in vitro transfection and also mice immunization by either intradermal injection or topical application. However, topical CSN-HIV pDNA vaccine complexes elicited statistically comparable immune response to naked HIV pDNA vaccine. The penetration study showed skin penetration pathways of nanoparticle-HIV pDNA vaccine were skin furrows and pilosebaceous unit.