Techniques for Follicular Penetration Studies

Main Article Content

Worranan Rangsimawong
Tanasait Ngawhirunpat

Abstract

Hair follicleswere an interesting target structure for drug delivery system. Although the total amount of hair and its follicles was only 0.1% of the total skin surface, they represent important shunt routes into the skin for hydrophilic drug and high molecular weight bio-molecules, as well as by particles-based drug delivery systems. Recently, many models have been developed for quantification of the delivery of drug into hair follicles. This review focuses on differential stripping and selective blocking of hair follicles technique, skin sandwich technique, and novel optical imaging system. For differential stripping technique, a combination of tape stripping and cyanoacrylate biopsies have led to quantify drug deposition in the upper hair follicles. In addition, selective blocking of hair follicles is widely used by selective sealing of hair follicles openings with micro-drops of a polymer-wax adhesive mixture to quantify drug retention in hair follicles. Secondly, skin sandwich model is an intriguing in vitro methodology that utilizes two human skin membranes, assuming that the additional stratum corneum blocks virtually all available follicular routes. However in this technique, transfollicular fate is determined and it is effective mostly for hydrophilic drugs only. Lastly, the use of novel optical imaging system, confocal laser scanning microscopy (CLSM) based techniques, can investigate semi-quantitatively the distribution of topically applied fluorescent dye in different skin layers and hair follicle structures.  In conclusion of this review, these techniques have been developed to quantify the delivery of drug into hair follicles that could provide a clearer information of the follicles as shunts for systemic drug delivery as opposed to their use as targets for local therapy.

Article Details

Section
Review Article

References

Alvarez-Roman R, Naik A, Kalia KN, et al. Visualization of skin penetration using confocal laser scanning microscopy. Eur J Pharm Biopharm 2004;58:301–316.

Asavapichayont P. Advanced techniques for skin delivery evaluation. In: Opanasopit P, editors. Technology diversity for pharmaceutical products development. 1st ed. Nakhonpathom: Petkasemprienting; 2011. 211-233.

Barry BW. Drug delivery routes in skin: a novel approach. Adv Drug Deliv Rev 2002; 54:31–40.

Bouwstra JA, Honeywell-Nguyen PL, Gooris GS, et al. Structure of the skin barrier and its modulation by vesicular formulations. Prog Lipid Res 2003;42(1):1–36.

Caspers PJ, Lucassen GW, Puppels GJ. Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin. Biophys J 2003;85: 572–580.

Desai P, Shah P, Hayden P, et al. Investigation of follicular and non-follicular pathways for Polyarginine and Oleic Acid-Modifi ed nanoparticles. Pharm Res 2013;30: 1037-1049.

El Maghraby GM, Williams AC, Barry BW. Skin hydration and possible shunt route penetration in controlled estradiol delivery from ultradeformable and standard liposomes. J Pharm Pharmacol 2001;53:

–1322. Essa EA, Bonner MC, Barry BW. Human skin sandwich for assessing shunt route penetration during passive and iontophoretic drug and liposome delivery. J Pharm Pharmacol 2002;54:1481–1491.

Gautier B, Bernard BA. On the use of Micro-Imager® to directly visualize drug distribution in human skin. Skin Pharmacol Appl Skin Physiol 2001;14:41–45.

Grams YY, Whitehead L, Cornwell P, et al. Time and depth resolved visualization of the diffusion of a lipophilic dye into the hair follicle of fresh unfi xed human scalp skin. J Control Release 2004;98:367–378.

Jacobi U, Taube H, Schafer UF, et al. Comparison of four different in vitro systems to study the reservoir capacity of the stratum corneum. J Control Release 2005;103: 61–71.

Knorr F, Lademann J, Patzelt A, et al. Follicular transport route-Research progress and future perspectives. Eur J Pharm Biopharm 2009;71:173-180.

Lademann J, Richter H, Teichmann A, et al. Nanoparticles--an effi cient carrier for drug delivery into the hair follicles. Eur J Pharm Biopharm 2007;66:159-164.

Lademann J, Richter H, Schanzer S, et al. Penetration and storage of particles in human skin: Perspectives and safety aspects. Eur J Pharm Biopharm 2011;77: 465–468.

Lauer AC, Lieb LM, Ramachandran C, et al. Transfollicular drug delivery. Pharm Res 1995;12:179–186.

Meidan V, Bonner M, Michniak B. Transfollicular drug delivery—Is it a reality?. Int J Pharm 2005;306:1–14.

Ogiso T, Shiraki T, Okajima K, et al. Transfollicular drug delivery: penetration of drugs through human scalp skin and comparison of penetration between scalp and abdominal skins in vitro. J Drug Target 2002;10(5):369-78.

Otberg N, Patzelt A, Rasulev U, et al. The role of hair follicles in the percutaneous absorption of caffeine. Br J Clin Pharmacol 2007; 65(4):488–492.

Patzelt A, Richter H, Buettemeyer R, et al. Differential stripping demonstrates a signifi cant reduction of the hair follicle reservoir in vitro compared to in vivo. Eur J Pharm Biopharm 2008;70:234–238.

Patzelt A, Richter H, Knorr F, et al. Selective follicular targeting by modifi cation of the particle sizes. J Control Release 2011; 150;45-48.

Raber AS, Mittal A, Schäfer J, et al. Quantifi cation of nanoparticle uptake into hair follicles in pig ear and human forearm. J Control Release 2014;179:25–32.

Sarheed O, Frum Y. Use of the skin sandwich technique to probe the role of the hair follicles in sonophoresis. Int J Pharm 2012;423:179-183.

Starcher B, Aycock RL, Hill CH. Multiple Roles for Elastic Fibers in the Skin. J Histochem Cytochem 2005;53:431–43.

Subongkot, T., Wonglertnirant, N., Songprakhon, P., et al. Visualization of ultradeformable liposomes penetration pathways and their skin interaction by confocal laser scanning microscopy. Int J Pharm 2013;441:151–161.

Teichmann A, Jacobi U, Ossadnik M, et al. Differential stripping: Determination of the amount of topically applied substances penetrated into the hair follicles. J Invest Dermatol 2005;125:264-269.

Teichmann A, Otberg N, Jacobi U, et al. Follicular penetration: development of a method to block the follicles selectively against the penetration of topically applied substances. Skin Pharmacol Physiol 2006;19:216–223.

Touitou E, Meidan VM, Horwitz E. Methods of quantitative determination of drug localised in the skin. J Control Release 1998;56:7-21.

Trauer S, Patzelt A, Otberg N, et al. Permeation of topically applied caffeine through human skin – a comparison of in vivo and in vitro data. Br J Clin Pharmacol 2009;68:181–186.

Vogt A, Hadam S, Heiderhoff M, et al. Morphometry of human terminal and vellus hair follicles. Exp Dermatol 2007;16:946–950.