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

Abstract

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-TNFα siRNA (siTNFα) 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 upto 360 µm 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 siTNFα showed significant reduced expression of TNFα, NF-κB, IL-17, IL-23 and Ki-67 genes compare to either drugs alone (p<0.05) and was in close comparison with Topgraf®;. Collectively these findings support our notion that novel cationic lipid-polymer hybrid nanoparticles can efficiently carry siTNFα and Cap into deeper dermal milieu and Cap with combination of siTNFα show synergism in treating skin inflammation.

Capsaicin-loaded nanolipoidal carriers for topical application: design, characterization, and in vitro/in vivo evaluation

“…33,34 In brief, confocal laser scanning microscopy (CLSM) was used to study the skin distribution and permeation mechanism of the Dio-NLCs, Dio-NLCs gel, and Dio solution. The amount of Dio dye applied remained the same for all preparations.…”

Topical Delivery System for Phytochemicals: Capsaicin and Capsicum Tincture

“…Hydroxypropyl-β-cyclodextrin complex was prepared as a mean to increase its transdermal delivery [11]. Several other novel drug delivery systems for capsaicin such as niosomes, microemulsions, lipid-polymer hybrid nanoparticles have also been developed [15,16].…”

TNF-&alpha; in the cardiovascular system: from physiology to therapy

“…206 Furthermore, several reports from the field of targeted drug delivery and nanomedicine appear to open promising possibilities for local or tissue-targeted TNF-α gene silencing. Two different topical delivery systems (cationic amphiphilic lipid particles 207 and capsaicin-loaded cationic lipid-polymer hybrid nanoparticles) 208 have recently demonstrated efficacy in local transport of anti-TNF-α small interfering (si)RNA and in the treatment of experimental psoriasis. Moreover, the problem of insufficient endothelial siRNA transfection efficiency in vivo has recently been overcome by Dahlman et al,209 who developed a polymeric nanoconstruct (7C1) capable of delivering siRNAs specifically to endothelial cells, which allowed concurrent silencing of multiple endothelial genes.…”