Enhanced transdermal delivery with less irritation by magainin pore-forming peptide with a N-lauroylsarcosine and sorbitan monolaurate mixture

Abstract

Transdermal drug delivery is advantageous over other conventional drug administration routes. However, it can be inefficient because of the natural barrier of the stratum corneum which is the uppermost layer of the skin. A previous study verified that the treatment of magainin pore-forming peptide with N-lauroylsarcosine (NLS) on human skin can increase skin permeability by 47-fold. However, NLS is well known as a potential skin irritant. The irritation potential of NLS is known to decrease when mixed with sorbitan monolaurate (S20). Encouraged by these results, we combined S20 with magainin-NLS to enhance transdermal drug transport with less skin irritation. In this study, nine groups with magainin and NLS:S20 mixtures at different concentrations and weight fractions were screened to maximize their synergistic effect. To quantify the efficacy to toxicity ratio of each formulation, we defined the ratio as the "enhancement ratio/irritation potential (ER/IP)." The ER was observed by Franz cell diffusion of the target drug fluorescein, and the IP was measured by the cytotoxicity of the NIH/3T3 mouse fibroblast cell line. As a result, the magainin with the NLS:S20 mixture increased the permeability of porcine skin as well as decreased the toxicity. Among the various combinations, a formulation of 2% (w/v) NLS:S20 with a weight fraction of 0.6:0.4 had the largest ER/IP. ATR-FTIR spectroscopy of the formulations and skin was done to analyze the interactions in the formulations themselves and between the formulations and the skin. Both the intercellular lipidic route and transcellular route through the stratum corneum protein were involved in the delivery of fluorescein. This study turned pore-forming peptides into an efficient and safe penetration enhancer by combining them with other chemical penetration enhancers. Moreover, this discovery could be a possible method for enabling the transdermal delivery of macromolecules.

Molecular Self-Assembly Strategy for Encapsulation of an Amphipathic α-Helical Antimicrobial Peptide into the Different Polymeric and Copolymeric Nanoparticles

“…On the other hand, changes in the helical structures in the presence of aforementioned nanomicelles can be carefully explored since the peptide helical structure is relatively small. Besides, Magainin2 has extensive antimicrobial activity and also to date is the only antimicrobial peptide that can enhance the transdermal transport of drug molecules. − In the present research, the molecular interactions of six types of polymers and copolymers with maganin2 in three different polymer/copolymer concentrations (100 mg/mL, 200 mg/mL, and 300 mg/mL) were investigated using all-atom MD simulations (Table ).…”

Enhanced recombinant protein capture, purity and yield from crude bacterial cell extracts by N-Lauroylsarcosine-assisted affinity chromatography

“…In this context, N-L is an anionic surfactant with multiple applications in biotechnology and biomedicine, including transdermal drug delivery [27][28][29], fabrication of biomaterials and nanomaterials [30][31][32], structural protein analysis [33,34], separation of co-purified tag-less proteins from protein complexes [35]and mild protein solubilization/extraction [36][37][38], among many others. In fact, it was the first non-denaturing agent used in the solubilization of recombinant proteins from IBs [39].…”

“…Also, in the line of potential obstacles for the use of N-L as a regular purification tool, the presence of detergent traces in the final product might pose severe health concerns. Indeed the presence of N-L and related surfactants in intravenous, oral, transdermal and colorectal drug formulations as protein stabilizer inhibits critical enzymes and raises several toxicological issues [28,[45][46][47]. Regarding the handling of N-L-treated samples, the working concentration used here (0.2%) is far below the limit of 1-30%, which corresponds to Eye Irritation 2, H319, and below the limit of > 30%, which corresponds to Skin Irritation 2, H315.…”

Therapeutic antibodies – natural and pathological barriers and strategies to overcome them

“…Overall, antibody treatment of lesions with intact skin epithelium remains challenging. New technologies investigate cell-penetrating peptides, physical penetration enhancer or injection with microneedles to help antibody cross the skin barrier ( Francis & Thomas, 2017 ; Gautam et al, 2016 ; Geh et al, 2019 ; Lee, Park, & Kim, 2018 ; Oberli, Schoellhammer, Langer, & Blankschtein, 2014 ), but none of them already achieved clinical success.…”