Dendrimer as a new potential carrier for topical delivery of siRNA: A comparative study of dendriplex vs. lipoplex for delivery of TNF-α siRNA.

Topical delivery of siRNA is challenging task due to complex barrier property of stratum corneum and cationic lipid based carriers have been widely explored for this purpose due to improved permeation through skin. For gene delivery application, dendrimers are considered as efficient carrier due to their cationic nature and well-defined surface groups. However, they are not well explored for topical delivery. This work compares the suitability of PAMAM dendrimer with DOTAP liposome for topical delivery of siRNA against TNF-α. The particle size, zeta potential and entrapment efficiency of dendriplex were 99.80 ± 1.80 nm, 13.40 ± 4.84 mV and 98.72 ± 2.02% whereas for lipoplex were 174.80 ± 0.80 nm, 29.96 ± 0.51 mV and 94.99 ± 5.01% respectively. Both the formulations were stable in serum and in the presence of RNAse. TNF-α is inflammatory cytokine, hence the in vivo efficacy of developed formulations was determined using psoriatic plaque model. Results suggested improved phenotypic and histopathological features and reduced levels of IL-6, TNF-α, IL-17 and IL-22 for dendriplex and lipoplex treated groups in comparison to Imiquimod treated group. These findings suggest that dendrimer can be a potential carrier for topical gene delivery.