Topical delivery of anti-TNFα siRNA and capsaicin via novel lipid-polymer hybrid nanoparticles efficiently inhibits skin inflammation in vivo

The barrier properties of the skin pose a significant but not insurmountable obstacle for development of new effective anti-inflammatory therapies. The objective of this study was to design and evaluate therapeutic efficacy of anti-nociception agent Capsaicin (Cap) and anti-TNF alpha siRNA (siTNF alpha) encapsulated cyclic cationic head lipid-polymer hybrid nanocarriers (CyLiPns) against chronic skin inflammatory diseases. Physico-chemical characterizations including hydrodynamic size, surface potential and entrapment efficacies of CyLiPns were found to be 163 +/- 9 nm, 35.14 +/- 8.23 mV and 92% for Cap, respectively. In vitro skin distribution studies revealed that CyLiPns could effectively deliver FITC-siRNA up to 360 mu m skin depth. Further, enhanced (p < 0.001) Cap permeation from CyLiPns was observed compared to Capsaicin-Solution and Capzasin-HP. Therapeutic efficacies of CyLiPns were assessed using imiquamod-induced psoriatic plaque like model. CyLiPns carrying both Cap and siTNF alpha showed significant reduced expression of TNF alpha, NF-kappa B, IL-17, IL-23 and Ki-67 genes compared to either drugs alone (p < 0.05) and were in close comparison with Topgraf (R). Collectively these findings support our notion that novel cationic lipid-polymer hybrid nanoparticles can efficiently carry siTNFa and Cap into deeper dermal milieu and Cap with a combination of siTNF alpha shows synergism in treating skin inflammation. (C) 2013 Elsevier B.V. All rights reserved.