Novel Vehicles For Drug Delivery In Atopic Dermatitis: A Narrative Review
Keywords:
atopic dermatitis, vehicle, crisaborole, tapinarofAbstract
Introduction: Atopic dermatitis (AD) causes dry and itchy skin and inflammation that severely impairs the quality of life of affected children and adults. While topical glucocorticosteroid application is typically the first-line treatment of choice, steroid treatment is associated with side effects and, increasingly, patient concerns about prolonged use. Novel drugs and drug delivery vehicles are required for patients with AD.
Objective: To summarize the current literature on novel topical agents for atopic dermatitis and novel delivery vehicles.
Methods: A literature search was conducted, and a narrative review was compiled to summarize recent evidence.
Results: Novel topical drugs approved or in late-phase clinical trials for the treatment of AD include the Janus kinase inhibitor ruxolitinib, the phosphodiesterase-4 inhibitors crisaborole, and roflumilast, and the aryl hydrocarbon receptor activator tapinarof. While current topical drugs for AD are delivered via creams, ointments, gels, and related vehicles, novel delivery approaches such as electrospun patches, sprays, liposomes, nanoparticles, and lasers are being developed to enhance transdermal delivery, reduce side effects, and increase treatment adherence.
Conclusion: Topical application of creams or ointments is currently the predominant vehicle for the delivery of atopic dermatitis drugs. In vitro studies on novel vehicles show promising results to overcome the issues associated with topical delivery. Still, these findings have to be corroborated by controlled studies with human patients in the future.
References
Urban K, Chu S, Giesey RL, et al. The global, regional, and national burden of atopic dermatitis in 195 countries and territories: An ecological study from the Global Burden of Disease Study 2017. JAAD International. 2021/03/01/ 2021;2:12-18. doi:https://doi.org/10.1016/j.jdin.2020.10.002
Bylund S, Kobyletzki LB, Svalstedt M, Svensson Å. Prevalence and Incidence of Atopic Dermatitis: A Systematic Review. Acta Derm Venereol. Jun 9 2020;100(12):adv00160. doi:10.2340/00015555-3510
Katoh N, Ohya Y, Ikeda M, et al. Clinical practice guidelines for the management of atopic dermatitis 2018. J Dermatol. Dec 2019;46(12):1053-1101. doi:10.1111/1346-8138.15090
Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. Feb 2014;70(2):338-51. doi:10.1016/j.jaad.2013.10.010
Katta R, Schlichte M. Diet and dermatitis: food triggers. J Clin Aesthet Dermatol. 2014;7(3):30-36.
Fujii M. The Pathogenic and Therapeutic Implications of Ceramide Abnormalities in Atopic Dermatitis. Cells. 2021;10(9):2386. doi:10.3390/cells10092386
Davis DMR, Drucker AM, Alikhan A, et al. American Academy of Dermatology Guidelines: Awareness of comorbidities associated with atopic dermatitis in adults. Journal of the American Academy of Dermatology. 2022;86(6):1335-1336.e18. doi:10.1016/j.jaad.2022.01.009
Müller SM, Tomaschett D, Euler S, Vogt DR, Herzog L, Itin P. Topical Corticosteroid Concerns in Dermatological Outpatients: A Cross-Sectional and Interventional Study. Dermatology. 2016;232(4):444-52. doi:10.1159/000446068
Buys LM. Treatment options for atopic dermatitis. Am Fam Physician. Feb 15 2007;75(4):523-8.
Axon E, Chalmers JR, Santer M, et al. Safety of topical corticosteroids in atopic eczema: an umbrella review. BMJ Open. 2021;11(7):e046476. doi:10.1136/bmjopen-2020-046476
Li AW, Yin ES, Antaya RJ. Topical Corticosteroid Phobia in Atopic Dermatitis: A Systematic Review. JAMA Dermatology. 2017;153(10):1036-1042. doi:10.1001/jamadermatol.2017.2437
Arkwright PD, Motala C, Subramanian H, Spergel J, Schneider LC, Wollenberg A. Management of difficult-to-treat atopic dermatitis. J Allergy Clin Immunol Pract. Mar 2013;1(2):142-51. doi:10.1016/j.jaip.2012.09.002
Drucker AM, Eyerich K, de Bruin-Weller MS, et al. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. The British journal of dermatology. 2018;178(3):768-775. doi:10.1111/bjd.15928
Quintás-Cardama A, Vaddi K, Liu P, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. Apr 15 2010;115(15):3109-17. doi:10.1182/blood-2009-04-214957
He H, Guttman-Yassky E. JAK Inhibitors for Atopic Dermatitis: An Update. Am J Clin Dermatol. Apr 2019;20(2):181-192. doi:10.1007/s40257-018-0413-2
Kim BS, Sun K, Papp K, Venturanza M, Nasir A, Kuligowski ME. Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle- and active-controlled study. J Am Acad Dermatol. Jun 2020;82(6):1305-1313. doi:10.1016/j.jaad.2020.02.009
Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. Feb 2020;145(2):572-582. doi:10.1016/j.jaci.2019.08.042
Papp K, Szepietowski JC, Kircik L, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. Oct 2021;85(4):863-872. doi:10.1016/j.jaad.2021.04.085
Bissonnette R, Call RS, Raoof T, et al. A Maximum-Use Trial of Ruxolitinib Cream in Adolescents and Adults with Atopic Dermatitis. Am J Clin Dermatol. May 2022;23(3):355-364. doi:10.1007/s40257-022-00690-3
Murrell DF, Gebauer K, Spelman L, Zane LT. Crisaborole Topical Ointment, 2% in Adults With Atopic Dermatitis: A Phase 2a, Vehicle-Controlled, Proof-of-Concept Study. J Drugs Dermatol. Oct 2015;14(10):1108-12.
Maurice DH, Ke H, Ahmad F, Wang Y, Chung J, Manganiello VC. Advances in targeting cyclic nucleotide phosphodiesterases. Nat Rev Drug Discov. Apr 2014;13(4):290-314. doi:10.1038/nrd4228
Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. Sep 2016;75(3):494-503.e6. doi:10.1016/j.jaad.2016.05.046
Heo JY, Cho YS, Cheon HG. Topical effects of roflumilast on 1-chloro-2,4-dinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. Pharmazie. Dec 2010;65(12):906-12.
Shen LF, Lv XD, Chen WY, Yang Q, Fang ZX, Lu WF. Effect of roflumilast on chronic obstructive pulmonary disease: a systematic review and meta-analysis. Ir J Med Sci. Aug 2018;187(3):731-738. doi:10.1007/s11845-018-1738-9
Bateman ED, Izquierdo JL, Harnest U, et al. Efficacy and safety of roflumilast in the treatment of asthma. Ann Allergy Asthma Immunol. May 2006;96(5):679-86. doi:10.1016/s1081-1206(10)61065-4
Arcutis Biotherapeutics, Inc.A. Phase 3, 4-Week, Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-151 Cream 0.15% Administered QD in Subjects With Atopic Dermatitis. ClinicalTrials.gov identifier: NCT04773587. Updated Septemberl 14, 2022. Accessed December 27, 2022. https://clinicaltrials.gov/ct2/show/NCT04773587
Smith SH, Jayawickreme C, Rickard DJ, et al. Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans. J Invest Dermatol. Oct 2017;137(10):2110-2119. doi:10.1016/j.jid.2017.05.004
Paller AS, Stein Gold L, Soung J, Tallman AM, Rubenstein DS, Gooderham M. Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis. J Am Acad Dermatol. Mar 2021;84(3):632-638. doi:10.1016/j.jaad.2020.05.135
Peppers J, Paller AS, Maeda-Chubachi T, et al. A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J Am Acad Dermatol. Jan 2019;80(1):89-98.e3. doi:10.1016/j.jaad.2018.06.047
Wollenberg A, Barbarot S, Bieber T, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. May 2018;32(5):657-682. doi:10.1111/jdv.14891
Stein Gold LF, Spelman L, Spellman MC, Hughes MH, Zane LT. A Phase 2, Randomized, Controlled, Dose-Ranging Study Evaluating Crisaborole Topical Ointment, 0.5% and 2% in Adolescents With Mild to Moderate Atopic Dermatitis. J Drugs Dermatol. Dec 2015;14(12):1394-9.
McDowell L, Olin B. Crisaborole: A Novel Nonsteroidal Topical Treatment for Atopic Dermatitis. J Pharm Technol. 2019;35(4):172-178. doi:10.1177/8755122519844507
Thom H, Cheng V, Keeney E, et al. Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis. Dermatol Ther (Heidelb). Jan 2022;12(1):185-194. doi:10.1007/s13555-021-00646-1
ClinicalTrials.gov. A Study of Crisaborole Ointment 2%; Crisaborole Vehicle; TCS and TCI in Subjects Aged ≥ 2 Years, With Mild-moderate AD. Accessed 01.11.2022, https://clinicaltrials.gov/ct2/show/results/NCT03539601?term=c3291037&draw=2&rank=1
Krysiak ZJ, Stachewicz U. Urea-Based Patches with Controlled Release for Potential Atopic Dermatitis Treatment. Pharmaceutics. Jul 19 2022;14(7)doi:10.3390/pharmaceutics14071494
Obaidat R, Shameh AA, Aljarrah M, Hamed R. Preparation and Evaluation of Polyvinylpyrrolidone Electrospun Nanofiber Patches of Pioglitazone for the Treatment of Atopic Dermatitis. AAPS PharmSciTech. Jan 10 2022;23(1):51. doi:10.1208/s12249-021-02204-6
Yang Y, Chen BZ, Zhang XP, et al. Conductive Microneedle Patch with Electricity-Triggered Drug Release Performance for Atopic Dermatitis Treatment. ACS Appl Mater Interfaces. Jul 20 2022;14(28):31645-31654. doi:10.1021/acsami.2c05952
Draelos ZD, Traub M, Gold MH, et al. Efficacy of Topical Botanical Treatment of Children With Mild to Moderate Atopic Dermatitis. J Drugs Dermatol. Oct 1 2019;18(10):1038-1045.
Draelos ZD, Traub M, Gold MH, et al. Validation of Botanical Treatment Efficiency for Adults and Children Suffering from Mild to Moderate Atopic Dermatitis. J Drugs Dermatol. Jun 1 2019;18(6):557.
Hogue L, Cardwell LA, Roach C, et al. Psoriasis and Atopic Dermatitis "Resistant" to Topical Treatment Responds Rapidly to Topical Desoximetasone Spray. J Cutan Med Surg. Mar/Apr 2019;23(2):157-163. doi:10.1177/1203475418818082
Zivkovich AH, Feldman SR. Are ointments better than other vehicles for corticosteroid treatment of psoriasis? J Drugs Dermatol. Jun 2009;8(6):570-2.
Naeimifar A, Ahmad Nasrollahi S, Samadi A, et al. Evaluation of tolerability and efficacy of a topical emulgel containing nanoliposomal ruxolitinib phosphate in the treatment of mild atopic dermatitis: A before-after single group pilot study. J Dermatolog Treat. Aug 9 2022:1-7. doi:10.1080/09546634.2022.2112138
Purohit VS, Ports WC, Wang C, Riley S. Systemic Tofacitinib Concentrations in Adult Patients With Atopic Dermatitis Treated With 2% Tofacitinib Ointment and Application to Pediatric Study Planning. J Clin Pharmacol. Jun 2019;59(6):811-820. doi:10.1002/jcph.1360
Purohit V, Riley S, Tan H, Ports WC. Predictors of Systemic Exposure to Topical Crisaborole: A Nonlinear Regression Analysis. J Clin Pharmacol. Oct 2020;60(10):1344-1354. doi:10.1002/jcph.1624
Damiani G, Eggenhöffner R, Pigatto PDM, Bragazzi NL. Nanotechnology meets atopic dermatitis: Current solutions, challenges and future prospects. Insights and implications from a systematic review of the literature. Bioactive materials. 2019;4:380-386. doi:10.1016/j.bioactmat.2019.11.003
Parekh K, Mehta TA, Dhas N, Kumar P, Popat A. Emerging Nanomedicines for the Treatment of Atopic Dermatitis. AAPS PharmSciTech. 2021/01/24 2021;22(2):55. doi:10.1208/s12249-021-01920-3
Pandey M, Choudhury H, Gunasegaran TAP, et al. Hyaluronic acid-modified betamethasone encapsulated polymeric nanoparticles: fabrication, characterisation, in vitro release kinetics, and dermal targeting. Drug Deliv Transl Res. Apr 2019;9(2):520-533. doi:10.1007/s13346-018-0480-1
Md S, Kuldeep Singh JKA, Waqas M, et al. Nanoencapsulation of betamethasone valerate using high pressure homogenization-solvent evaporation technique: optimization of formulation and process parameters for efficient dermal targeting. Drug Dev Ind Pharm. Feb 2019;45(2):323-332. doi:10.1080/03639045.2018.1542704
Siddique MI, Katas H, Jamil A, et al. Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects. Drug Deliv Transl Res. Apr 2019;9(2):469-481. doi:10.1007/s13346-017-0439-7
Siddique MI, Tufail S, Ker ZH, et al. Towards fast and cost-effective up-scaling of Nano-encapsulations by Ionic-gelation method using model drug for the treatment of atopic dermatitis. Pak J Pharm Sci. Sep 2019;32(5(Supplementary)):2299-2304.
Sahle FF, Gerecke C, Kleuser B, Bodmeier R. Formulation and comparative in vitro evaluation of various dexamethasone-loaded pH-sensitive polymeric nanoparticles intended for dermal applications. Int J Pharm. Jan 10 2017;516(1-2):21-31. doi:10.1016/j.ijpharm.2016.11.029
Zhuo F, Abourehab MAS, Hussain Z. Hyaluronic acid decorated tacrolimus-loaded nanoparticles: Efficient approach to maximize dermal targeting and anti-dermatitis efficacy. Carbohydr Polym. Oct 1 2018;197:478-489. doi:10.1016/j.carbpol.2018.06.023
Yu K, Wang Y, Wan T, et al. Tacrolimus nanoparticles based on chitosan combined with nicotinamide: enhancing percutaneous delivery and treatment efficacy for atopic dermatitis and reducing dose. Int J Nanomedicine. 2018;13:129-142. doi:10.2147/ijn.S150319
Choi JK, Park JY, Lee S, et al. Greater Plasma Protein Adsorption on Mesoporous Silica Nanoparticles Aggravates Atopic Dermatitis. Int J Nanomedicine. 2022;17:4599-4617. doi:10.2147/ijn.S383324
Kalia YN, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery. Adv Drug Deliv Rev. Mar 27 2004;56(5):619-58. doi:10.1016/j.addr.2003.10.026
Le QV, Howard A. Dexamethasone iontophoresis for the treatment of nail psoriasis. Australas J Dermatol. May 2013;54(2):115-9. doi:10.1111/ajd.12029
Dasht Bozorg B, Bhattaccharjee SA, Somayaji MR, Banga AK. Topical and transdermal delivery with diseased human skin: passive and iontophoretic delivery of hydrocortisone into psoriatic and eczematous skin. Drug Deliv Transl Res. Jan 2022;12(1):197-212. doi:10.1007/s13346-021-00897-7
Bissonnette R, Pavel AB, Diaz A, et al. Crisaborole and atopic dermatitis skin biomarkers: An intrapatient randomized trial. J Allergy Clin Immunol. Nov 2019;144(5):1274-1289. doi:10.1016/j.jaci.2019.06.047
Callender VD, Alexis AF, Stein Gold LF, et al. Efficacy and Safety of Crisaborole Ointment, 2%, for the Treatment of Mild-to-Moderate Atopic Dermatitis Across Racial and Ethnic Groups. Am J Clin Dermatol. Oct 2019;20(5):711-723. doi:10.1007/s40257-019-00450-w
Cheape AC, Murrell DF. 2% Crisaborole topical ointment for the treatment of mild-to-moderate atopic dermatitis. Expert Rev Clin Immunol. May 2017;13(5):415-423. doi:10.1080/1744666x.2017.1304820
Draelos ZD, Stein Gold LF, Murrell DF, Hughes MH, Zane LT. Post Hoc Analyses of the Effect of Crisaborole Topical Ointment, 2% on Atopic Dermatitis: Associated Pruritus from Phase 1 and 2 Clinical Studies. J Drugs Dermatol. Feb 2016;15(2):172-6.
Eichenfield LF, Call RS, Forsha DW, et al. Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis. J Am Acad Dermatol. Oct 2017;77(4):641-649.e5. doi:10.1016/j.jaad.2017.06.010
Eichenfield LF, Yosipovitch G, Stein Gold LF, et al. Improvement in disease severity and pruritus outcomes with crisaborole ointment, 2%, by baseline atopic dermatitis severity in children and adolescents with mild-to-moderate atopic dermatitis. Pediatr Dermatol. Nov 2020;37(6):1030-1037. doi:10.1111/pde.14328
Fujita K, Yagi M, Moriwaki S, Yoshida M, Graham D. A phase 2b, randomized, double-blind, multicenter, vehicle-controlled study to assess the efficacy and safety of two crisaborole regimens in Japanese patients aged 2 years and older with mild-to-moderate atopic dermatitis. J Dermatol. Nov 2021;48(11):1640-1651. doi:10.1111/1346-8138.16120
Schlessinger J, Shepard JS, Gower R, et al. Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1). Am J Clin Dermatol. Apr 2020;21(2):275-284. doi:10.1007/s40257-020-00510-6
Silverberg JI, Tallman AM, Ports WC, Gerber RA, Tan H, Zielinski MA. Evaluating the Efficacy of Crisaborole Using the Atopic Dermatitis Severity Index and Percentage of Affected Body Surface Area. Acta Derm Venereol. Jun 11 2020;100(13):adv00170. doi:10.2340/00015555-3489
Spergel JM, Blaiss MS, Lio P, et al. Efficacy and safety of crisaborole in patients with mild-to-moderate atopic dermatitis and other atopic comorbidities. Allergy Asthma Proc. Sep 1 2021;42(5):425-431. doi:10.2500/aap.2021.42.210064
Bissonnette R, Vasist LS, Bullman JN, Collingwood T, Chen G, Maeda-Chubachi T. Systemic Pharmacokinetics, Safety, and Preliminary Efficacy of Topical AhR Agonist Tapinarof: Results of a Phase 1 Study. Clin Pharmacol Drug Dev. Jun 2018;7(5):524-531. doi:10.1002/cpdd.439
Keam SJ. Tapinarof Cream 1%: First Approval. Drugs. Jul 2022;82(11):1221-1228. doi:10.1007/s40265-022-01748-6
Published
Issue
Section
License
Copyright (c) 2023 Christopher Farkouh, Michelle Anthony, Parsa Abdi, Natalia Santiago, Matthew Farkouh
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Dermatology Practical & Conceptual applies a Creative Commons Attribution License (CCAL) to all works we publish (http://creativecommons.org/licenses/by-nc/4.0/). Authors retain the copyright for their published work.
How to Cite
Share
