Polymeric nanoparticles‐based topical delivery systems for the treatment of dermatological diseases

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Zheng Zhang, Pei‐Chin Tsai, Tannaz Ramezanli, Bozena B. Michniak‐Kohn

Published Online: Feb 05 2013

DOI: 10.1002/wnan.1211

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Abstract Human skin not only functions as a permeation barrier (mainly because of the stratum corneum layer) but also provides a unique delivery pathway for therapeutic and other active agents. These compounds penetrate via intercellular, intracellular, and transappendageal routes, resulting in topical delivery (into skin strata) and transdermal delivery (to subcutaneous tissues and into the systemic circulation). Passive and active permeation enhancement methods have been widely applied to increase the cutaneous penetration. The pathology, pathogenesis, and topical treatment approaches of dermatological diseases, such as psoriasis, contact dermatitis, and skin cancer, are then discussed. Recent literature has demonstrated that nanoparticles‐based topical delivery systems can be successful in treating these skin conditions. The studies are reviewed starting with the nanoparticles based on natural polymers especially chitosan, followed by those made of synthetic, degradable (aliphatic polyesters), and nondegradable (polyacrylates) polymers; emphasis is given to nanospheres made of polymers derived from naturally occurring metabolites, the tyrosine‐derived nanospheres (TyroSpheres™). In summary, the nanoparticles‐based topical delivery systems combine the advantages of both the nanosized drug carriers and the topical approach, and are promising for the treatment of skin diseases. For the perspectives, the penetration of ultra‐small nanoparticles (size smaller than 40 nm) into skin strata, the targeted delivery of the encapsulated drugs to hair follicle stem cells, and the combination of nanoparticles and microneedle array technologies for special applications such as vaccine delivery are discussed. WIREs Nanomed Nanobiotechnol 2013, 5:205–218. doi: 10.1002/wnan.1211 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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A schematic image of epidermis, dermis, and hypodermis structure. The appendages such as hair shaft and hair follicle, sweat gland, sebaceous gland, and arrector pili muscle are illustrated.

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Tyrosine‐derived, ABA‐type poly(ethylene glycol)‐b‐oligo(desaminotyrosyl‐tyrosine octyl ester suberate)‐b‐poly(ethylene glycol) triblock copolymer used in the preparation of Tyrospheres™.

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Standard of care for psoriasis categorized as systemic approach, phototherapy, and topical approach. Under each category, the current treatment options (on the left columns) and the side effects (on the right columns) are given.

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An overview of passive and active skin penetration enhancement methods.

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References

Holbrook, KA, Wolff, K. The structure and development of skin. In: Fitzpatrick, TB, Eisen, AZ, Wolff, K, Freedberg, IM, Austen, KF, eds. Dermatology in General Medicine. New York, NY: McGraw‐Hill; 1987, 93–131.
Scheuplein, RJ, Blank, IH. Permeability of the skin. Physiol Rev 1971, 51:702–747.
Cotsarelis, G. Epithelial stem cells: a folliculocentric view. J Invest Dermatol. 2006, 126:1459–1468.
Paudel, KS, Milewski, M, Swadley, CL, Brogden, NK, Ghosh, P, Stinchcomb, AL. Challenges and opportunities in dermal/transdermal delivery. Ther Deliv 2010, 1:109–131.
Hadgraft, J, Guy, RH. Feasibility assessment in topical and transdermal delivery: mathematical models and in vitro studies. In: Guy, RH, Hadgraft, J, eds. Transdermal Drug Delivery. 2nd ed. New York, NY: Marcel Dekker, Inc.; 2003, 1–23.
Higuchi, T. Physical chemical analysis of percutaneous absorption process from creams and ointments. J Soc Cosmet Chem 1960, 11:85–97.
Alvarez‐Roman, R, Naik, A, Kalia, YN, Guy, RH, Fessi, H. Skin penetration and distribution of polymeric nanoparticles. J Control Release 2004, 99:53–62.
Zhang, Q, Grice, JE, Li, P, Jepps, OG, Wang, GJ, Roberts, MS. Skin solubility determines maximum transepidermal flux for similar size molecules. Pharm Res 2009, 26:1974–1985.
Moser, K, Kriwet, K, Naik, A, Kalia, YN, Guy, RH. Passive skin penetration enhancement and its quantification in vitro. Eur J Pharm Biopharm 2001, 52:103–112.
Barry, BW. Penetration enhancer classification. In: Smith, EW, Maibach, HI, eds. Percutaneous Penetration Enhancers. 2nd ed. New York, NY: Taylor and Francis; 2006, 3–16.
Alvarez‐Roman, R, Naik, A, Kalia, YN, Guy, RH, Fessi, H. Enhancement of topical delivery from biodegradable nanoparticles. Pharm Res 2004, 21:1818–1825.
Cormier, M, Johnson, B, Ameri, M, Nyam, K, Libiran, L, Zhang, DD, Daddona, P. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release 2004, 97:503–511.
Akomeah, FK, Martin, GP, Muddle, AG, Brown, MB. Effect of abrasion induced by a rotating brush on the skin permeation of solutes with varying physicochemical properties. Eur J Pharm Biopharm 2008, 68:724–734.
Alvarez‐Roman, R, Merino, G, Kalia, YN, Naik, A, Guy, RH. Skin permeability enhancement by low frequency sonophoresis: lipid extraction and transport pathways. J Pharm Sci 2003, 92:1138–1146.
Mori, K, Hasegawa, T, Sato, S, Sugibayashi, K. Effect of electric field on the enhanced skin permeation of drugs by electroporation. J Control Release 2003, 90:171–179.
Harvey, AJ, Kaestner, SA, Sutter, DE, Harvey, NG, Mikszta, JA, Pettis, RJ. Microneedle‐based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs. Pharm Res 2011, 28:107–116.
Fukushima, K, Ise, A, Morita, H, Hasegawa, R, Ito, Y, Sugioka, N, Takada, K. Two‐layered dissolving microneedles for percutaneous delivery of peptide/protein drugs in rats. Pharm Res 2011, 28:7–21.
Coulman, SA, Barrow, D, Anstey, A, Gateley, C, Morrissey, A, Wilke, N, Allender, C, Brain, K, Birchall, JC. Minimally invasive cutaneous delivery of macromolecules and plasmid DNA via microneedles. Curr Drug Deliv 2006, 3:65–75.
Quan, FS, Kim, YC, Compans, RW, Prausnitz, MR, Kang, SM. Dose sparing enabled by skin immunization with influenza virus‐like particle vaccine using microneedles. J Control Release 2010, 147:326–332.
Bowcock, AM, Krueger, JG. Getting under the skin: the immunogenetics of psoriasis. Nat Rev Immunol 2005, 5:699–711.
Clark, RA, Kupper, TS. Misbehaving macrophages in the pathogenesis of psoriasis. J Clin Invest 2006, 116:2084–2087.
Danilenko, DM. Review paper: preclinical models of psoriasis. Vet Pathol 2008, 45:563–575.
Van de Kerkhof, PC, Vissers, WH. Established treatments of psoriasis. Curr Drug Targets Inflamm Allergy 2004, 3:145–156.
Naldi, L, Griffiths, CE. Traditional therapies in the management of moderate to severe chronic plaque psoriasis: an assessment of the benefits and risks. Br J Dermatol 2005, 152:597–615.
Andersen, KE, Benezra, C, Burrows, D, Camarasa, J, Dooms‐Goossens, A, Ducombs, G, Frosch, P, Lachapelle, JM, Lahti, A, Menné, T, et al. Contact dermatitis. A review. Contact Dermatitis 1987, 16:55–78.
Nosbaum, A, Vocanson, M, Rozieres, A, Hennino, A, Nicolas, JF. Allergic and irritant contact dermatitis. Eur J Dermatol 2009, 19:325–332.
Plake, KS, Darbishire, PL. Contact dermatitis. In: Krinsky, DL, Berardi, RR, Ferreri, SP, Hume, AL, Newton, GD, Rollins, CJ, Tietze, KJ, eds. APhA Handbook of Nonprescription Drugs, an Interactive Approach to Self‐Care. Washington, DC: American Pharmacists Association; 2012, 645–660, Chapter 34.
Narayanan, DL, Saladi, RN, Fox, JL. Ultraviolet radiation and skin cancer. Int J Dermatol 2010, 49:978–986.
Bendesky, A, Michel, A, Sordo, M, Calderon‐Aranda, ES, Acosta‐Saavedra, LC, Salazar, AM, Podoswa, N, Ostrosky‐Wegman, P. DNA damage, oxidative mutagen sensitivity, and repair of oxidative DNA damage in nonmelanoma skin cancer patients. Environ Mol Mutagen 2006, 47:509–517.
Kanjilal, S, Strom, SS, Clayman, GL, Weber, RS, el‐Naggar, AK, Kapur, V, Cummings, KK, Hill, LA, Spitz, MR, Kripke, ML, et al. p53 mutations in nonmelanoma skin cancer of the head and neck: molecular evidence for field cancerization. Cancer Res 1995, 55:3604–3609.
Ro, YS. Oncogene interaction in basal cell carcinomas of human skin. J Korean Med Sci 1995, 10:85–92.
Dréau, D, Culberson, C, Wyatt, S, Holder, WD. Human papilloma virus in melanoma biopsy specimens and its relation to melanoma progression. Ann Surg 2000, 231:664–671.
Williams, AC. Topical 5‐FU—a new approach to skin cancer. Ann Surg 1971, 173:864–871.
Urosevic, M, Dummer, R. Role of imiquimod in skin cancer treatment. Am J Clin Dermatol 2004, 5:453–458.
Longley, DB, Harkin, DP, Johnston, PG. 5‐Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003, 3:330–338.
Matsumura, Y, Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent Smancs. Cancer Res 1986, 46:6387–6392.
Guterres, SS, Alves, MP, Pohlmann, AR. Polymeric nanoparticles, nanospheres and nanocapsules, for cutaneous applications. Drug Target Insights 2007, 2:147–157.
Lee, RW, Shenoy, DB, Sheel, R. Micellar nanoparticles: applications for topical and passive transdermal drug delivery. In: Kulkarni, VS, ed. Handbook of Non‐Invasive Drug Delivery Systems. Burlington, MA: Elsevier Inc.; 2010, 37–58, Chapter 2.
Vandervoort, J, Ludwig, A. Preparation and evaluation of drug‐loaded gelatin nanoparticles for topical ophthalmic use. Eur J Pharm Biopharm 2004, 57:251–261.
Patel, M, Jain, SK, Yadav, AK, Gogna, D, Agrawal, GP. Preparation and characterization of oxybenzone‐loaded gelatin microspheres for enhancement of sunscreening efficacy. Drug Deliv 2006, 13:323–330.
Kim, DG, Jeong, YI, Choi, C, Roh, SH, Kang, SK, Jang, MK, Nah, JW. Retinol‐encapsulated low molecular water‐soluble chitosan nanoparticles. Int J Pharm 2006, 319:130–138.
Ozbas‐Turan, S, Akbuga, J, Sezer, AD. Topical application of antisense oligonucleotide‐loaded chitosan nanoparticles to rats. Oligonucleotides 2010, 20: 147–153.
Hasanovic, A, Zehl, M, Reznicek, G, Valenta, C. Chitosan‐tripolyphosphate nanoparticles as a possible skin drug delivery system for aciclovir with enhanced stability. J Pharm Pharmacol 2009, 61:1609–1616.
Ozbas‐Turan, S, Akbuga, J. Plasmid DNA‐loaded chitosan/TPP nanoparticles for topical gene delivery. Drug Deliv 2011, 18:215–222.
Şenyiğit, T, Sonvico, F, Barbieri, S, Ozer, O, Santi, P, Colombo, P. Lecithin/chitosan nanoparticles of clobetasol‐17‐propionate capable of accumulation in pig skin. J Control Release 2010, 142:368–373.
Tan, Q, Liu, W, Guo, C, Zhai, G. Preparation and evaluation of quercetin‐loaded lecithin‐chitosan nanoparticles for topical delivery. Int J Nanomed 2011, 6:1621–1630.
Shahnaz, G, Vetter, A, Barthelmes, J, Rahmat, D, Laffleur, F, Iqbal, J, Perera, G, Schlocker, W, Dunnhaput, S, Augustijns, P, et al. Thiolated chitosan nanoparticles for the nasal administration of leuprolide: bioavailability and pharmacokinetic characterization. Int J Pharm 2012, 428:164–170.
de la Fuente, M, Seijo, B, Alonso, MJ. Bioadhesive hyaluronan‐chitosan nanoparticles can transport genes across the ocular mucosa and transfect ocular tissue. Gene Ther 2008, 15:668–676.
Chuah, LH, Billa, N, Roberts, CJ, Burley, JC, Manickam, S. Curcumin‐containing chitosan nanoparticles as a potential mucoadhesive delivery system to the colon. Pharm Dev Technol 2011, 1–9. doi: 10.3109/ 10837450.2011.640688.
Panyam, J, Labhasetwar, V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 2003, 55:329–347.
Tsujimoto, H, Hara, K, Tsukada, Y, Huang, CC, Kawashima, Y, Arakaki, M, Okayasu, H, Mimura, H, Miwa, N. Evaluation of the permeability of hairgrowing ingredient encapsulated PLGA nanospheres to hair follicles and their hairgrowing effects. Bioorg Med Chem Lett 2007, 17:4771–4777.
Tomoda, K, Terashima, H, Suzuki, K, Inagi, T, Terada, H, Makino, K. Enhanced transdermal delivery of indomethacin‐loaded PLGA nanoparticles by iontophoresis. Colloids Surf B Biointerfaces 2011, 88:706–710.
Shah, PP, Desai, PR, Patel, AR, Singh, MS. Skin permeating nanogel for the cutaneous co‐delivery of two anti‐inflammatory drugs. Biomaterials 2012, 33:1607–1617.
Alvarez‐Roman, R, Barre, G, Guy, RH, Fessi, H. Biodegradable polymer nanocapsules containing a sunscreen agent: preparation and photoprotection. Eur J Pharm Biopharm 2001, 52:191–195.
Shim, J, Seok Kang, H, Park, WS, Han, SH, Kim, J, Chang, IS. Transdermal delivery of mixnoxidil with block copolymer nanoparticles. J Control Release 2004, 97:477–484.
Wu, X, Price, GJ, Guy, RH. Disposition of nanoparticles and an associated lipophilic permeant following topical application to the skin. Mol Pharm 2009, 6:1441–1448.
Turos, E, Shim, JY, Wang, Y, Greenhalgh, K, Suresh Kumar Reddy, GS, Dickey, S, Lim, DV. Antibiotic‐conjugated polyacrylate nanoparticles: new opportunities for development of anti‐MRSA agents. Bioorg Med Chem Lett 2007, 17:53–56.
Greenhalgh, K, Turos, E. In vivo studies of polyacrylate nanoparticle emulsions for topical and systemic applications. Nanomedicine 2009, 5:46–54.
Sheihet, L, Piotrowska, K, Dubin, RA, Kohn, J, Devore, D. Effect of tyrosine‐derived triblock copolymer compositions on nanosphere self‐assembly and drug delivery. Biomacromolecules 2007, 8:998–1003.
Kilfoyle, BE, Sheihet, L, Zhang, Z, Laohoo, M, Kohn, J, Michniak‐Kohn, BB. Development of paclitaxel‐TyroSpheres for topical skin treatment. J Control Release 2012, 163:18–24. doi: 10.1016/j.jconrel.2012.06.021.
Sheihet, L, Garbuzenko, OB, Bushman, J, Gounder, MK, Minko, T, Kohn, J. Paclitaxel in tyrosine‐derived nanospheres as a potential anti‐cancer agent: in vivo evaluation of toxicity and efficacy in comparison with paclitaxel in Cremophor. Eur J Pharm Sci 2012, 45:320–329.
Batheja, P, Sheihet, L, Kohn, J, Singer, AJ, Michniak‐Kohn, B. Topical drug delivery by a polymeric nanosphere gel: formulation optimization and in vitro and in vivo skin distribution studies. J Control Release 2011, 149:159–167.
Sheihet, L, Chandra, P, Batheja, P, Devore, D, Kohn, J, Michniak, B. Tyrosine‐derived nanospheres for enhanced topical skin penetration. Int J Pharm 2008, 350:312–319.
Tang, BC, Dawson, M, Lai, SK, Wang, YY, Suk, JS, Yang, M, Zeitlin, P, Boyle, MP, Fu, J, Hanes, J. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci U S A 2009, 106:19268–19273.
Choi, HS, Ashitate, Y, Lee, JH, Kim, SH, Matsui, A, Insin, N, Bawendi, MG, Semmler‐Behnke, M, Frangioni, JV, Tsuda, A. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol 2010, 28:1300–1303.
Zheng, D, Giljohann, DA, Chen, DL, Massich, MD, Wang, XQ, Iordanov, H, Mirkin, CA, Paller, AS. Topical delivery of siRNA‐based spherical nucleic acid nanoparticle conjugates for gene regulation. Proc Natl Acad Sci U S A 2012, 109:11975–11980.
Zhang, W, Gao, J, Zhu, Q, Zhang, M, Ding, X, Wang, X, Hou, X, Fan, W, Ding, B, Wu, X, et al. Penetration and distribution of PLGA nanoparticles in the human skin treated with microneedles. Int J Pharm 2010, 402:205–212.
Coulman, SA, Anstey, A, Gateley, C, Morrissey, A, McLoughlin, P, Allender, C, Birchall, JC. Microneedle mediated delivery of nanoparticles into human skin. Int J Pharm 2009, 366:190–200.
del Pilar Martin, M, Weldon, WC, Zarnitsyn, VG, Koutsonanos, DG, Akbari, H, Skountzou, I, Jacob, J, Prausnitz, MR, Compans, RW. Local response to microneedle‐based influenza immunization in the skin. MBio 2012, 3. doi: 10.1128/mBio.00012‐12.

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