The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years

Topical and transdermal delivery systems are of undeniable significance and ubiquity in healthcare, to facilitate the delivery of active pharmaceutical ingredients, respectively, onto or across the skin to enter systemic circulation. From ancient ointments and potions to modern micro/nanotechnological devices, a variety of approaches has been explored over the ages to improve the skin permeation of diverse medicines and cosmetics. Amongst the latest investigational dermal permeation enhancers, ionic liquids have been gaining momentum, and recent years have been prolific in this regard. As such, this review offers an outline of current methods for enhancing percutaneous permeation, highlighting selected reports where ionic liquid-based approaches have been investigated for this purpose. Future perspectives on use of ionic liquids for topical delivery of bioactive peptides are also presented.

Piroxicam Percutaneous Permeation from Gels Through Membrane Models of Shed Snakeskin and Cellulose

Skin has a very important role in determining percutaneous absorption of active substance in topical administration. Study on percutaneous permeation of piroxicam from gel had been conducted using Franz Diffusion Cell with membrane model of shed snakeskin and cellulose. Piroxicam gels were made using Aqupec HV-505 base with 0; 2.5; 5; and 7.5% of DMSO as an enhancer. The results showed that the most stable gel preparation was the one with 5% DMSO (F2), so it was used for further investigation to which percutaneous permeation test. The permeation test was conducted in preparation without and with 5% DMSO (F2) in vitro through shed snakeskin and cellulose membranes. The results showed that F2 increased the permeation rate by as much as 0.0281% per minute. In comparison, the permeation rate of formulation without DMSO (F0) was 0.012% per minute. It can be concluded that DMSO can increase piroxicam penetration through shed snakeskin. Permeation study using cellulose membrane on formula F2 revealed permeation rate as much as 0.006% per minute whereas that without DMSO (F0) was 0.0112% per minute.Keywords: DMSO, cellulose membrane, percutaneous permeation, piroxicam, shed snakeskin.

Freezing Weakens the Barrier Function of Reconstructed Human Epidermis as Evidenced by Raman Spectroscopy and Percutaneous Permeation

The development and characterization of reconstructed human epidermis (RHE) is an active area of R&D. RHE can replace animal tissues in pharmaceutical, toxicological and cosmetic sciences, yielding scientific and ethical advantages. RHEs remain costly, however, due to consumables and time required for their culture and a short shelf-life. Storing, i.e., freezing RHE could help reduce costs but to date, little is known on the effects of freezing on the barrier function of RHE. We studied such effects using commercial EpiSkin™ RHE stored at −20, −80 and −150 °C for 1 and 10 weeks. We acquired intrinsic Raman spectra in the stratum corneum (SC) of the RHEs as well as spectra obtained following topical application of resorcinol in an aqueous solution. In parallel, we quantified the effects of freezing on the permeation kinetics of resorcinol from time-dependent permeation experiments. Principal component analyses discriminated the intrinsic SC spectra and the spectra of resorcinol-containing RHEs, in each case on the basis of the freezing conditions. Permeation of resorcinol through the frozen RHE increased 3- to 6-fold compared to fresh RHE, with the strongest effect obtained from freezing at −20 °C for 10 weeks. Due to the extensive optimization and standardization of EpiSkin™ RHE, the effects observed in our work may be expected to be more pronounced with other RHEs.

Sulforaphane-Loaded Ultradeformable Vesicles as A Potential Natural Nanomedicine for the Treatment of Skin Cancer Diseases

Sulforaphane is a multi-action drug and its anticancer activity is the reason for the continuous growth of attention being paid to this drug. Sulforaphane shows an in vitro antiproliferative activity against melanoma and other skin cancer diseases. Unfortunately, this natural compound cannot be applied in free form on the skin due to its poor percutaneous permeation determined by its physico-chemical characteristics. The aim of this investigation was to evaluate ethosomes® and transfersomes® as ultradeformable vesicular carriers for the percutaneous delivery of sulforaphane to be used for the treatment of skin cancer diseases. The physico-chemical features of the ultradeformable vesicles were evaluated. Namely, ethosomes® and transfersomes® had mean sizes <400 nm and a polydispersity index close to 0. The stability studies demonstrated that the most suitable ultradeformable vesicles to be used as topical carriers of sulforaphane were ethosomes® made up of ethanol 40% (w/v) and phospholipon 90G 2% (w/v). In particular, in vitro studies of percutaneous permeation through human stratum corneum and epidermis membranes showed an increase of the percutaneous permeation of sulforaphane. The antiproliferative activity of sulforaphane-loaded ethosomes® was tested on SK-MEL 28 and improved anticancer activity was observed in comparison with the free drug.

BOX–BEHNKEN METHOD TO OPTIMIZE LORNOXICAM PRONIOSOMES: PREPARATION, IN VITRO CHARACTERIZATION AND ANALGESIC ACTIVITY

The objective of present investigation was to develop and evaluation of proniosomes as the carrier of lornoxicam for topical delivery. lornoxicam-loaded proniosomes were prepared by coacervation phase separation method. The Box–Behnken design used in this study helped in identifying the factors affecting drug entrapment efficiency and drug diffusion. Proniosomes were evaluated for appearance, pH, viscosity, entrapment efficiency and in vitro drug diffusion studies. The optimized formulations were further evaluated to vesicle size, shape, zeta potential, percutaneous permeation and analgesic effect. The vesicles were found to be unilamellar, spherical in shape. The analgesic effect of lornoxicam proniosomal gel showed better therapeutic activity.