Influence of Piperine on Transcutaneous Permeation of Repaglinide in Rats and on Tight Junction Proteins in HaCaT Cells: Unveiling the Mechanisms for Enhanced Permeation

Abstract

The purpose of this study was to evaluate the influence of piperine on permeation of repaglinide (RGE) across rat epidermis. In addition, the role of chitosan (CTN) and its combination with piperine was investigated for exploring the possibility of further enhancing the permeation of RGE. The permeation of RGE across excised rat epidermis was, respectively, ~4-fold, ~5-fold and ~6-fold higher when piperine (0.008% w/v), CTN (1% w/v), or piperine -CTN mixture was used as donor vehicle as compared to propylene glycol: ethanol (PG: EtOH) (7:3) mixture. The merger of T2 and T3 (lipid-specific) and obliteration of T4 (protein-specific) endothermic transitions in the thermograms of excised rat epidermis suggested overwhelming influence of these treatments on skin lipids and proteins. Further, the observed increase in intercellular space, disordering of lipid structure and corneocyte detachment indicated considerable effect on the ultrastructure of rat epidermis. The enhancement in permeation of RGE across rat epidermis excised after various treatments for different periods was correlated with the transepidermal water loss of similarly treated viable rat skin the cell walls only marginally. However, remarkable decrease in the immunofluorescence of anti-TJP1 (ZO-1) antibody was observed after treatment of HaCaT cells with mixture of piperine and CTN. The systemic delivery of RGE in rats was enhanced by 8-fold and 9.5-fold from transdermal formulations containing, respectively, piperine (0.008 % w/v) or piperine (0.008 % w/v)-CTN (1% w/v) mixture as enhancer. Overall, the observations suggested overwhelming influence of piperine and CTN on ZO-1 protein to be responsible for enhancing the percutaneous permeation of RGE.

Effect of Piperine on Skin Permeation of Curcumin from a Bacterially Derived Cellulose-Composite Double-Layer Membrane for Transdermal Curcumin Delivery

“…In previous studies, piperine has been used as a transdermal enhancer for several drugs [26,27] but it has not been used for curcumin. The permeation of curcumin when used in combination with piperine was 2-8 times higher than that of curcumin alone.…”