Investigation of Different Iontophoretic Currents Profiles for Short-Term Applications in Cosmetics

[EN] This study aimed at investigating the effect of electrical current profile upon the iontophoretic transport of (i) ascorbic acid (AA) and (ii) ellagic acid (EA), into porcine skin in vitro, and the impact of the physicochemical properties of both actives on their mechanism of transport when formulated in cosmetic compositions. The experiments were performed using a proprietary iontophoretic device containing a roller to apply the formulation. Three current profiles were tested: (i) galvanic direct current (DC), (ii) square unipolar pulse current (SPC), and (iii) galvanic direct current (DC) + pulse current (PC). The skin samples were collected at different sampling points, extracted and analyzed by HPLC. Results suggested that the DC + PC mode for only 5 min was able to significantly increase the delivery of AA from o/w cosmetic compositions. The use of this current profile might improve the skin penetration of AA due to electromigration and passive diffusion, the latter being facilitated by the physical enhancement method. The SPC mode significantly improved the passage of EA in its neutral form from cosmetic o/w formulations by electroosmosis. Tailoring specific electrical current modes considering the ionization state of active ingredients would allow the design of short and personalized cosmetic treatments that significantly improve the penetration efficiency of the active ingredients and possibly reduce the doses applied.This research was entirely funded by L'Oreal, France.Cázares-Delgadillo, J.; Planard-Luong, L.; Gregoire, S.; Serna-Jiménez, CE.; Singhal, M.; Kalia, YN.; Merino Sanjuán, V.... (2018). Investigation of Different Iontophoretic Currents Profiles for Short-Term Applications in Cosmetics. Pharmaceutics. 10(4). https://doi.org/10.3390/pharmaceutics10040266266104R. Hamad, A.-W., Al-Momani, W. M., Janakat, S., & A. Oran, S. (2009). Bioavailability of Ellagic Acid After Single Dose Administration Using HPLC. Pakistan Journal of Nutrition, 8(10), 1661-1664. doi:10.3923/pjn.2009.1661.1664Kalia, Y. N., Naik, A., Garrison, J., & Guy, R. H. (2004). Iontophoretic drug delivery. Advanced Drug Delivery Reviews, 56(5), 619-658. doi:10.1016/j.addr.2003.10.026Marro, D., Kalia, Y. N., Begoña Delgado‐Charro, M., & Guy, R. H. (2001). Pharmaceutical Research, 18(12), 1701-1708. doi:10.1023/a:1013318412527Sobhi, R. M., & Sobhi, A. M. (2012). A single-blinded comparative study between the use of glycolic acid 70% peel and the use of topical nanosome vitamin C iontophoresis in the treatment of melasma. Journal of Cosmetic Dermatology, 11(1), 65-71. doi:10.1111/j.1473-2165.2011.00599.xHori, Y., Akimoto, R., Hori, A., Kato, K., Chino, D., Matsumoto, S., … Watanabe, Y. (2010). Skin collagen reproduction increased by ascorbic acid derivative iontophoresis by frequent-reversal bipolar electric stimulation. International Journal of Cosmetic Science, 32(3), 234-234. doi:10.1111/j.1468-2494.2010.00577_3.xJunyaprasert, V. B., Singhsa, P., Suksiriworapong, J., & Chantasart, D. (2012). Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of ellagic acid. International Journal of Pharmaceutics, 423(2), 303-311. doi:10.1016/j.ijpharm.2011.11.032Maia, A. M., Baby, A. R., Pinto, C. A. S. O., Yasaka, W. J., Suenaga, E., Kaneko, T. M., & Velasco, M. V. R. (2006). Influence of sodium metabisulfite and glutathione on the stability of vitamin C in O/W emulsion and extemporaneous aqueous gel. International Journal of Pharmaceutics, 322(1-2), 130-135. doi:10.1016/j.ijpharm.2006.05.03

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

Cutaneous Delivery and Biodistribution of Cannabidiol in Human Skin after Topical Application of Colloidal Formulations

The objective of this study was to investigate the cutaneous delivery of cannabidiol (CBD) from aqueous formulations developed for the targeted local treatment of dermatological conditions. CBD was formulated using a proprietary colloidal drug delivery system (VESIsorb®) into an aqueous colloidal solution at 2% (ACS 2%) and two colloidal gels (CG 1% and CG 2%, which contained 1% and 2% CBD, respectively). Two basic formulations containing CBD (5% in propylene glycol (PG 5%) and a 6.6% oil solution (OS 6.6%)) and two marketed CBD products (RP1 and RP2, containing 1% CBD) were used as comparators. Cutaneous delivery and cutaneous biodistribution experiments were performed using human abdominal skin (500–700 µm) under infinite- and finite-dose conditions with 0.5% Tween 80 in the PBS receiver phase. The quantification of CBD in the skin samples was performed using a validated UHPLC-MS/MS method and an internal standard (CBD-d3). The cutaneous deposition of CBD under finite-dose conditions demonstrated the superiority of CG 1%, CG 2%, and ACS 2% over the marketed products; CG 1% had the highest delivery efficiency (5.25%). Cutaneous biodistribution studies showed the superiority of the colloidal systems in delivering CBD to the viable epidermis, and the upper and lower papillary dermis, which are the target sites for the treatment of several dermatological conditions

Non-Invasive Iontophoretic Delivery of Cytochrome c to the Posterior Segment and Determination of Its Ocular Biodistribution

The intact porcine eye globe model was used to demonstrate that transscleral iontophoresis could deliver a small protein, cytochrome c (Cyt c), to the posterior segment and to investigate post-iontophoretic biodistribution in the different ocular compartments. The effects of Cyt c concentration (1, 5, and 10 mg/mL), current density (3.5 and 5.5 mA/cm2), and duration of the current application (10 min and 1, 2, and 4 h) were evaluated. The data confirmed that transscleral iontophoresis enhanced the intraocular delivery of Cyt c under all conditions as compared to passive controls (same setup but without the current application). Increasing the Cyt c concentration resulted in a proportional enhancement in the Cyt c delivery. Increasing the current density from 3.5 to 5.5 mA/cm2 increased iontophoretic delivery at a Cyt c concentration of 10 mg/mL but did not appear to do so at 5 mg/mL; this was attributed in part to the effect of melanin binding. Short duration iontophoresis (10 min, 3.5 mA/cm2) of a 10 mg/mL Cyt c solution created a depot in the sclera. When this was followed by a 4 h incubation period, post-iontophoretic Cyt c diffusion from the sclera resulted in a different biodistribution, and Cyt c could be quantified in the posterior segment

The effect of current on skin barrier function in vivo: recovery kinetics post-iontophoresis

The objective of this study was to determine the extent to which current passage perturbed the skin's intrinsic permeability, and to quantify how quickly and to what extent the barrier properties recovered from the effects of iontophoresis

Simultaneous Delivery of Econazole, Terbinafine and Amorolfine with Improved Cutaneous Bioavailability: A Novel Micelle-Based Antifungal “Tri-Therapy”

Lack of accurate diagnosis and the use of formulations designed to address the poor aqueous solubility of antifungal agents, but not optimized for delivery, contribute to unsatisfactory outcomes for topical treatment of cutaneous mycoses. The objective of this study was to develop a micelle-based antifungal formulation containing econazole (ECZ), terbinafine (TBF) and amorolfine (AMF) using D-α-tocopheryl polyethylene glycol succinate (TPGS) for simultaneous cutaneous delivery of three agents with complementary mechanisms of action. The antifungal “tri-therapy” micelle-based formulation containing 0.1% ECZ, 0.1% TBF and 0.025% AMF had a drug loading 10-fold lower than the “reference” marketed formulations (Pevaryl®, 1% ECZ; Lamisil®, 1% TBF; Loceryl®, 0.25% AMF). Finite dose application of the micelle-based formulation for 6 h resulted in a statistically equivalent deposition of ECZ (p > 0.05) and TBF (p > 0.05) from the 2 systems, and a 2-fold higher accumulation of AMF (p = 0.017). Antifungal concentrations above MIC80 against Trichophyton rubrum were achieved in each skin layer with the “tri-therapy”, which also exhibited a preferential deposition of each antifungal agent in pilosebaceous unit (PSU)-containing biopsies as compared with PSU-free biopsies (p < 0.05). A planned clinical study will test whether these promising results translate to improved therapeutic outcomes in vivo

Drug Transport across Porcine Intestine Using an Ussing Chamber System: Regional Differences and the Effect of P-Glycoprotein and CYP3A4 Activity on Drug Absorption

Drug absorption across viable porcine intestines was investigated using an Ussing chamber system. The apparent permeability coefficients, Papp,pig, were compared to the permeability coefficients determined in humans in vivo, Peff,human. Eleven drugs from the different Biopharmaceutical Classification System (BCS) categories absorbed by passive diffusion with published Peff,human values were used to test the system. The initial experiments measured Papp,pig for each drug after application in a Krebs–Bicarbonate Ringer (KBR) buffer and in biorelevant media FaSSIF V2 and FeSSIF V2, mimicking fasted and fed states. Strong sigmoidal correlations were observed between Peff,human and Papp,pig. Differences in the segmental Papp,pig of antipyrine, cimetidine and metoprolol confirmed the discrimination between drug uptake in the duodenum, jejunum and ileum (and colon); the results were in good agreement with human data in vivo. The presence of the P-gp inhibitor verapamil significantly increased Papp,pig across the ileum of the P-gp substrates cimetidine and ranitidine (p < 0.05). Clotrimazole, a potent CYP3A4 inhibitor, significantly increased Papp,pig of the CYP3A4 substrates midazolam, verapamil and tamoxifen and significantly decreased the formation of their main metabolites. In conclusion, the results showed that this is a robust technique to predict passive drug permeability under fasted and fed states, to identify regional differences in drug permeability and to demonstrate the activity of P-gp and CYP3A4

Transdermal patches: History, development and pharmacology

Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems