Enhanced skin penetration of P20 phosphopeptide using protein transduction domains

Abstract

Protein transduction domains (PTDs) were recently demonstrated to increase the penetration of the model peptide P20 when the PTD and P20 were covalently attached. Here, we evaluated whether non-covalently linked PTDs were capable of increasing the skin penetration of P20. Two different PTDs were studied: YARA and WLR. Porcine ear skin mounted in a Franz diffusion cell was used to assess the penetration of P20 in the stratum corneum (SC) and viable skin (VS); VS consists of dermis and epidermis without SC. The transdermal delivery of P20 was also assessed. At 1 mM, YARA promoted a 2.33-fold increase in the retention of P20 in the SC but did not significantly increase the amount of P20 that reached VS. WLR significantly increased (2.88-fold) the penetration of P20 in VS. Compared to the non-attached form, the covalently linked WLR fragment was two times more effective in promoting the penetration of P20 into VS. None of the PTDs promoted transdermal delivery of P20 at 4 h post-application. It was concluded that selected non-covalently linked PTDs can be used as a penetration enhancer, but greater skin penetration efficiency can be achieved by covalently binding the PTD to the therapeutic agent.

Combining poly-arginine with the hydrophobic counter-anion 4-(1-pyrenyl)-butyric acid for protein transduction in transdermal delivery

“…Previous studies have showed the effective transdermal skin delivery of proteins and peptides employing CPPs including Tat (Trans-activating transcriptional activator), YARA, WLR, and 9R peptides [26][27][28][29]. In the present study, we also showed that protein transduction method using 11R was valuable for the transdermal delivery of EGFP and HQ.…”

Potent enhancement of transdermal absorption and stability of human tyrosinase plasmid (pAH7/Tyr) by Tat peptide and an entrapment in elastic cationic niosomes

“…This result was correlated to previous studies which showed that the interaction of the CPPs including Tat peptide with skin lipids may be the main transport across the SC, since this interaction may destabilize the SC resulting in an increase in the membrane permeability (Rothbard et al, 2000). Another suggested mechanism of transport was via the tight junctions which allowed penetration into the viable skin layers (Lopes et al, 2008). Kang et al (2010) studied the in vitro and in vivo skin penetration effect of Tat-coated elastic liposomes, they found that the Tat peptide could increase the flux of the liposomes by about 20%.…”

Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in Nc/Nga mice

“…This result is consistent with an earlier report that stated that the noncovalent WLR fragment, one of the penetrating peptides, was twice as effective in promoting the penetration of macromolecules into the skin. 19 It is also supported by an earlier report stating that several penetrating peptides are able to interact with lipids in the stratum corneum and enter into a layer of cells via a macropinocytosis mechanism, forming a gradient from the outer to the inner cell layers, thus facilitating the delivery of drug. 39 …”

“…Some experiments have demonstrated that cell-penetrating peptides including YARA, WLR, R9, and Tat (Trans-activating transcriptional activator) peptides were useful not only for intracellular delivery but also for promoting the skin penetration of molecules in mice. 19,20 A recent study showed that Tat peptide facilitates the translocation of drugs into immune cells in the skin. 21 Therefore, a novel Tat peptide-admixed EL (EL/T) containing HST was developed.…”