{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T23:12:14Z","timestamp":1773357134132,"version":"3.50.1"},"reference-count":100,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Photodynamic therapy is one of the more unique cancer treatment options available in today\u2019s arsenal against this devastating disease. It has historically been explored in cutaneous lesions due to the possibility of focal\/specific effects and minimization of adverse events. Advances in drug delivery have mostly been based on biomaterials, such as liposomal and hybrid lipoidal vesicles, nanoemulsions, microneedling, and laser-assisted photosensitizer delivery systems. This review summarizes the most promising approaches to enhancing the photosensitizers\u2019 transdermal delivery efficacy for the photodynamic treatment for cutaneous pre-cancerous lesions and skin cancers. Additionally, discussions on strategies and advantages in these approaches, as well as summarized challenges, perspectives, and translational potential for future applications, will be discussed.<\/jats:p>","DOI":"10.3390\/ph14080772","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T08:01:42Z","timestamp":1628236902000},"page":"772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Micro- and Nano-Based Transdermal Delivery Systems of Photosensitizing Drugs for the Treatment of Cutaneous Malignancies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6448-2550","authenticated-orcid":false,"given":"Isabella","family":"Portugal","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia Industrial, Universidade Tiradentes, Aracaju 49032-490, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5999-931X","authenticated-orcid":false,"given":"Sona","family":"Jain","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia Industrial, Universidade Tiradentes, Aracaju 49032-490, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia","family":"Severino","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Biotecnologia Industrial, Universidade Tiradentes, Aracaju 49032-490, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-0405","authenticated-orcid":false,"given":"Ronny","family":"Priefer","sequence":"additional","affiliation":[{"name":"Massachusetts College of Pharmacy and Health Sciences, University, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5946\/ce.2013.46.1.24","article-title":"Photodynamic therapy (PDT): PDT mechanisms","volume":"46","author":"Allison","year":"2013","journal-title":"Clin. Endosc."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hamblin, M.R., and Abrahamse, H. (2018). Inorganic salts and antimicrobial photodynamic therapy: Mechanistic conundrums?. Molecules, 23.","DOI":"10.3390\/molecules23123190"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vallejo, M., Moura, N.M.M., Ferreira Faustino, M.A., Almeida, A., Gon\u00e7alves, I., Serra, V.V., and Neves, M.G.P.M.S. (2020). An insight into the role of non-porphyrinoid photosensitizers for skin wound healing. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010234"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vallejo, M.C.S., Moura, N.M.M., Gomes, A.T.P.C., Joaquinito, A.S.M., Faustino, M.A.F., Almeida, A., Gon\u00e7alves, I., Serra, V.V., and Neves, M.G.P.M.S. (2021). The role of porphyrinoid photosensitizers for skin wound healing. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084121"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102318","DOI":"10.1016\/j.pdpdt.2021.102318","article-title":"Application of photodynamic therapy in immune-related diseases","volume":"34","author":"Yang","year":"2021","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1213\/ANE.0b013e31828f29da","article-title":"Measuring mitochondrial oxygen tension: From basic principles to application in humans","volume":"117","author":"Mik","year":"2013","journal-title":"Anesth. Analg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3389\/fchem.2021.691697","article-title":"Photodynamic therapy\u2014Current limitations and novel approaches","volume":"9","author":"Gunaydin","year":"2021","journal-title":"Front. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1365-2818.2005.01471.x","article-title":"Porphyrin-related photosensitizers for cancer imaging and therapeutic applications","volume":"218","author":"Berg","year":"2005","journal-title":"J. Microsc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nrc1071","article-title":"Photodynamic therapy for cancer","volume":"3","author":"Dolmans","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","first-page":"1","article-title":"The use of a derivative of hematoporhyrin in tumor detection","volume":"26","author":"Lipson","year":"1961","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/jnci\/55.1.115","article-title":"Photoradiation therapy. II. Cure of animal tumors with hematoporphyrin and light23","volume":"55","author":"Dougherty","year":"1975","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_12","first-page":"2628","article-title":"Photoradiation therapy for the treatment of malignant tumors","volume":"38","author":"Dougherty","year":"1978","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"van Straten, D., Mashayekhi, V., de Bruijn, H.S., Oliveira, S., and Robinson, D.J. (2017). Oncologic photodynamic therapy: Basic principles, current clinical status and future directions. Cancers, 9.","DOI":"10.3390\/cancers9020019"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40824-018-0140-z","article-title":"Clinical development of photodynamic agents and therapeutic applications","volume":"22","author":"Baskaran","year":"2018","journal-title":"Biomater. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.det.2014.03.009","article-title":"Photodynamic Therapy","volume":"32","author":"Rkein","year":"2014","journal-title":"Dermatol. Clin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.biopha.2018.07.049","article-title":"Photodynamic therapy-mechanisms, photosensitizers and combinations","volume":"106","author":"Kwiatkowski","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chizenga, E.P., and Abrahamse, H. (2020). Nanotechnology in modern photodynamic therapy of cancer: A review of cellular resistance patterns affecting the therapeutic response. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070632"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"24381","DOI":"10.3402\/nano.v5.24381","article-title":"Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma","volume":"5","author":"Muehlmann","year":"2014","journal-title":"Nano Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101979","DOI":"10.1016\/j.jddst.2020.101979","article-title":"Non-porphyrin dyes used as photosensitizers in photodynamic therapy","volume":"60","author":"Priefer","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1590\/S0100-879X2011007500091","article-title":"Liposomal photosensitizers: Potential platforms for anticancer photodynamic therapy","volume":"44","author":"Muehlmann","year":"2011","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_21","first-page":"1","article-title":"Controlled drug delivery vehicles for cancer treatment and their performance","volume":"3","author":"Senapati","year":"2018","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2174\/1874126600701010036","article-title":"Innovative strategies for enhancing topical and transdermal drug delivery","volume":"1","author":"Morrow","year":"2007","journal-title":"Open Drug Deliv. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/srt.12968","article-title":"Methods for evaluating penetration of drug into the skin: A review","volume":"27","author":"Supe","year":"2021","journal-title":"Ski. Res. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Keservani, R.K., Bandopadhyay, S., Bandyopadhyay, N., and Sharma, A.K. (2020). Design and fabrication of transdermal\/skin drug-delivery system. Drug Delivery Systems, Elsevier.","DOI":"10.1016\/B978-0-12-814487-9.00004-1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3109\/09687688.2010.522203","article-title":"Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery","volume":"27","author":"Desai","year":"2010","journal-title":"Mol. Membr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.addr.2003.10.028","article-title":"Lipid vesicles and other colloids as drug carriers on the skin","volume":"56","author":"Cevc","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1517\/17425247.2.3.477","article-title":"Liposomal delivery of photosensitising agents","volume":"2","author":"Chen","year":"2005","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S1011-1344(01)00118-X","article-title":"Increase of the photosensitizing efficiency of the Bacteriochlorin a by liposome-incorporation","volume":"60","author":"Damoiseau","year":"2001","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.addr.2003.07.014","article-title":"Liposomes for photodynamic therapy","volume":"56","author":"Derycke","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/1061186X.2013.765442","article-title":"The application of nanoemulsion in dermatology: An overview","volume":"21","author":"Wu","year":"2013","journal-title":"J. Drug Target."},{"key":"ref_31","unstructured":"Becher, P. (2001). Emulsions: Theory and Practice, Oxford University Press."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1023\/A:1007612905378","article-title":"Photodynamic therapy of skin cancers: Sensitizers, clinical studies and future directives","volume":"17","author":"Bentley","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S1011-1344(01)00133-6","article-title":"The photosensitizing effect of the photoproduct of protoporphyrin IX","volume":"60","author":"Ma","year":"2001","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.2174\/092986706776360888","article-title":"Aminolevulinic acid derivatives and liposome delivery as strategies for improving 5-aminolevulinic acid-mediated photodynamic therapy","volume":"13","author":"Casas","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_35","first-page":"e302","article-title":"Fluorescence induction of protoporphyrin IX by a new 5-aminolevulinic acid nanoemulsion used for photodynamic therapy in a full-thickness ex vivo skin model","volume":"19","author":"Maisch","year":"2009","journal-title":"Exp. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1159\/000329025","article-title":"Treatment with 5-Aminolaevulinic acid methylester is less painful than treatment with 5-Aminolaevulinic acid nanoemulsion in topical photodynamic therapy for actinic keratosis","volume":"222","author":"Gholam","year":"2011","journal-title":"Dermatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.2217\/fon-2017-0247","article-title":"A review of BF-200 ALA for the photodynamic treatment of mild-to-moderate actinic keratosis","volume":"13","author":"Reinhold","year":"2017","journal-title":"Future Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1365-2133.2010.09873.x","article-title":"Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: Results of a prospective, randomized, double-blind, placebo-controlled phase III study","volume":"163","author":"Szeimies","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/j.1365-2133.2011.10613.x","article-title":"Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: Results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo","volume":"166","author":"Dirschka","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/jdv.15185","article-title":"A randomized, intraindividual, non-inferiority, Phase III study comparing daylight photodynamic therapy with BF-200 ALA gel and MAL cream for the treatment of actinic keratosis","volume":"33","author":"Dirschka","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Collier, N.J., and Rhodes, L.E. (2020). Photodynamic therapy for basal cell carcinoma: The clinical context for future research priorities. Molecules, 25.","DOI":"10.3390\/molecules25225398"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1166\/jnn.2008.18137","article-title":"Photophysical studies and in vitro skin permeation\/retention of Foscan\/nanoemulsion (NE) applicable to photodynamic therapy skin cancer treatment","volume":"8","author":"Primo","year":"2008","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jmmm.2006.10.1183","article-title":"Magnetic nanoemulsions as drug delivery system for Foscan\u00ae: Skin permeation and retention in vitro assays for topical application in photodynamic therapy (PDT) of skin cancer","volume":"311","author":"Primo","year":"2007","journal-title":"J. Magn. Magn. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e211","DOI":"10.1016\/j.jmmm.2008.02.050","article-title":"In vitro studies of cutaneous retention of magnetic nanoemulsion loaded with zinc phthalocyanine for synergic use in skin cancer treatment","volume":"320","author":"Primo","year":"2008","journal-title":"J. Magn. Magn. Mater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jconrel.2016.09.008","article-title":"Transdermal delivery from liposomal formulations-Evolution of the technology over the last three decades","volume":"242","author":"Ashtikar","year":"2016","journal-title":"J. Control Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.drudis.2013.04.003","article-title":"Current status of liposomal porphyrinoid photosensitizers","volume":"18","author":"Piskorz","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1468-3083.2009.03100.x","article-title":"Liposomes in dermatology today","volume":"23","author":"Bjerring","year":"2009","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1365-2133.2000.03711.x","article-title":"The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization","volume":"143","author":"Casas","year":"2000","journal-title":"Br. J. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ejps.2011.07.003","article-title":"Retained topical delivery of 5-aminolevulinic acid using cationic ultradeformable liposomes for photodynamic therapy","volume":"44","author":"Oh","year":"2011","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-5945-1-5","article-title":"Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: Preparation and in vitro permeation study","volume":"1","author":"Pierre","year":"2001","journal-title":"BMC Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1046\/j.1365-2133.2002.04715.x","article-title":"In vitro\/in vivo correlations between transdermal delivery of 5-aminolaevulinic acid and cutaneous protoporphyrin IX accumulation and effect of formulation","volume":"146","author":"Tsai","year":"2002","journal-title":"Br. J. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1038\/sj.bjc.6601722","article-title":"Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies","volume":"90","author":"Perotti","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/lsm.20739","article-title":"Fluorescence detection and diagnosis of non-melanoma skin cancer at an early stage","volume":"41","author":"Neugebauer","year":"2009","journal-title":"Lasers Surg. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"630","DOI":"10.2478\/s11658-010-0033-1","article-title":"In vitro and in vivo matrix metalloproteinase expression after photodynamic therapy with a liposomal formulation of aminolevulinic acid and its methyl ester","volume":"15","author":"Osiecka","year":"2010","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.biopha.2015.05.002","article-title":"Improved anti-melanoma effect of a transdermal mitoxantrone ethosome gel","volume":"73","author":"Yu","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0168-3659(99)00222-9","article-title":"Ethosomes\u2014Novel vesicular carriers for enhanced delivery: Characterization and skin penetration properties","volume":"65","author":"Touitou","year":"2000","journal-title":"J. Control. Release"},{"key":"ref_57","first-page":"100027","article-title":"Mechanism investigation of ethosomes transdermal permeation","volume":"1","author":"Niu","year":"2019","journal-title":"Int. J. Pharm. X"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ijpharm.2008.01.020","article-title":"Comparison of 5-aminolevulinic acid-encapsulated liposome versus ethosome for skin delivery for photodynamic therapy","volume":"356","author":"Fang","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ejpb.2009.07.011","article-title":"Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior","volume":"73","author":"Fang","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.ijpharm.2015.08.036","article-title":"Development and ex vivo evaluation of 5-aminolevulinic acid-loaded niosomal formulations for topical photodynamic therapy","volume":"494","author":"Bragagni","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1615\/JEnvironPatholToxicolOncol.v26.i2.60","article-title":"Fluorescence monitoring of a topically applied liposomal temoporfin formulation and photodynamic therapy of nonpigmented skin malignancies","volume":"26","author":"Bendsoe","year":"2007","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"034026","DOI":"10.1117\/1.2743080","article-title":"Fluorescence and absorption assessment of a lipid mTHPC formulation following topical application in a non-melanotic skin tumor model","volume":"12","author":"Johansson","year":"2007","journal-title":"J. Biomed. Opt."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/j.1939-1676.2007.tb03020.x","article-title":"Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: Preliminary results concerning drug safety and efficacy","volume":"21","author":"Buchholz","year":"2007","journal-title":"J. Vet. Intern. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jphotobiol.2008.01.009","article-title":"Topical application of temoporfin-loaded invasomes for photodynamic therapy of subcutaneously implanted tumours in mice: A pilot study","volume":"91","author":"Albrecht","year":"2008","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ijpharm.2009.10.006","article-title":"Surface charged temoporfin-loaded flexible vesicles: In vitro skin penetration studies and stability","volume":"384","author":"Gitter","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.colsurfb.2009.07.005","article-title":"Development of liposomes containing ethanol for skin delivery of temoporfin: Characterization and in vitro penetration studies","volume":"74","author":"Scheglmann","year":"2009","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s10103-012-1256-3","article-title":"Topical photodynamic therapy using transfersomal aluminum phthalocyanine tetrasulfonate: In vitro and in vivo study","volume":"28","author":"Kassab","year":"2013","journal-title":"Lasers Med. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.dyepig.2013.08.018","article-title":"Preparation, characterization, and in vitro phototoxic effect of zinc phthalocyanine cucurbit [7] uril complex encapsulated into liposomes","volume":"100","author":"Bolfarini","year":"2014","journal-title":"Dye. Pigment."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.pdpdt.2017.05.013","article-title":"Ultradeformable liposome loaded with zinc phthalocyanine and [Ru(NH.NHq)(tpy)NO] 3+ for photodynamic therapy by topical application","volume":"19","author":"Tedesco","year":"2017","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.ijpharm.2018.06.057","article-title":"Dermal delivery of Fe-chlorophyllin via ultradeformable nanovesicles for photodynamic therapy in melanoma animal model","volume":"548","author":"Rady","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.molliq.2018.09.034","article-title":"Formulation of chloroaluminum phthalocyanine incorporated into PS-b-PAA diblock copolymer nanomicelles","volume":"271","author":"Vilsinski","year":"2018","journal-title":"J. Mol. Liq."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.pdpdt.2018.10.002","article-title":"Skin permeation, biocompatibility and antitumor effect of chloroaluminum phthalocyanine associated to oleic acid in lipid nanoparticles","volume":"24","author":"Almeida","year":"2018","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"12321","DOI":"10.1021\/acsami.9b00361","article-title":"Facile fabrication of nanoscale porphyrinic covalent organic polymers for combined photodynamic and photothermal cancer therapy","volume":"11","author":"Shi","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.pdpdt.2017.01.186","article-title":"Liposomal delivery of ferrous chlorophyllin: A novel third generation photosensitizer for in vitro PDT of melanoma","volume":"18","author":"Gomaa","year":"2017","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"118528","DOI":"10.1016\/j.ijpharm.2019.118528","article-title":"Ethosomes and lipid-coated chitosan nanocarriers for skin delivery of a chlorophyll derivative: A potential treatment of squamous cell carcinoma by photodynamic therapy","volume":"568","author":"Nasr","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/lsm.22769","article-title":"Challenges to laser-assisted drug delivery: Applying theory to clinical practice","volume":"50","author":"Ibrahim","year":"2018","journal-title":"Lasers Surg. Med."},{"key":"ref_77","first-page":"858","article-title":"Laser-assisted drug delivery","volume":"109","author":"Boixeda","year":"2018","journal-title":"Actas Dermosifiliogr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1517\/17425247.2014.885501","article-title":"Lasers as an approach for promoting drug delivery via skin","volume":"11","author":"Lin","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/jps.20577","article-title":"In vitro percutaneous absorption and in vivo protoporphyrin IX accumulation in skin and tumors after topical 5-aminolevulinic acid application with enhancement using an erbium:YAG laser","volume":"95","author":"Shen","year":"2006","journal-title":"J. Pharm. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/lsm.20860","article-title":"Fractional CO2 laser-assisted drug delivery","volume":"42","author":"Haedersdal","year":"2010","journal-title":"Lasers Surg. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/lsm.21096","article-title":"Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment","volume":"43","author":"Haedersdal","year":"2011","journal-title":"Lasers Surg. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/lsm.22259","article-title":"Pretreatment with ablative fractional laser changes kinetics and biodistribution of topical 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL)","volume":"46","author":"Haedersdal","year":"2014","journal-title":"Lasers Surg. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"425","DOI":"10.36849\/JDD.2020.4589","article-title":"Treating field cancerization by ablative fractional laser and indoor daylight: Assessment of efficacy and tolerability","volume":"19","author":"Paasch","year":"2020","journal-title":"J. Drugs Dermatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10103-015-1835-1","article-title":"Fractional radiofrequency combined with sonophoresis to facilitate skin penetration of 5-aminolevulinic acid","volume":"31","author":"Park","year":"2016","journal-title":"Lasers Med. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/lsm.23125","article-title":"A new method for percutaneous drug delivery by thermo-mechanical fractional injury","volume":"52","author":"Shavit","year":"2020","journal-title":"Lasers Surg. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.pdpdt.2016.06.012","article-title":"Plum-blossom needling promoted PpIX fluorescence intensity from 5-aminolevulinic acid in porcine skin model and patients with actnic keratosis","volume":"15","author":"Chen","year":"2016","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"120410","DOI":"10.1016\/j.biomaterials.2020.120410","article-title":"Progress and perspective of microneedle system for anti-cancer drug delivery","volume":"264","author":"Li","year":"2021","journal-title":"Biomaterials"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jconrel.2008.05.002","article-title":"Microneedle-mediated intradermal delivery of 5-aminolevulinic acid: Potential for enhanced topical photodynamic therapy","volume":"129","author":"Donnelly","year":"2008","journal-title":"J. Control. Release"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1751-1097.2008.00417.x","article-title":"Microneedle arrays permit enhanced intradermal delivery of a preformed photosensitizer","volume":"85","author":"Donnelly","year":"2009","journal-title":"Photochem. Photobiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.pdpdt.2010.09.001","article-title":"Microneedle-mediated intradermal nanoparticle delivery: Potential for enhanced local administration of hydrophobic pre-formed photosensitisers","volume":"7","author":"Donnelly","year":"2010","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/php.12209","article-title":"Hydrogel-forming and dissolving microneedles for enhanced delivery of photosensitizers and precursors","volume":"90","author":"Donnelly","year":"2014","journal-title":"Photochem. Photobiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"667","DOI":"10.4155\/fmc.09.55","article-title":"Designing photosensitizers for photodynamic therapy: Strategies, challenges and promising developments","volume":"1","author":"Garland","year":"2009","journal-title":"Future Med. Chem."},{"key":"ref_93","first-page":"A43","article-title":"Microfabricated microneedles: A novel strategy for enhancing topical delivery of 5-aminolevulinic acid and preformed photosensitisers: 117","volume":"58","author":"Morrow","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.pdpdt.2014.09.003","article-title":"Potential of microneedles in enhancing delivery of photosensitising agents for photodynamic therapy","volume":"11","author":"Kearney","year":"2014","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jconrel.2018.07.038","article-title":"Tip-loaded fast-dissolving microneedle patches for photodynamic therapy of subcutaneous tumor","volume":"286","author":"Zhao","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jconrel.2016.08.015","article-title":"5-Aminolevulinic acid coated microneedles for photodynamic therapy of skin tumors","volume":"239","author":"Jain","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1016\/j.xphs.2018.05.017","article-title":"Intradermal delivery of a near-infrared photosensitizer using dissolving microneedle arrays","volume":"107","author":"Hamdan","year":"2018","journal-title":"J. Pharm. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"11936","DOI":"10.1021\/acsnano.8b03007","article-title":"Microneedle-assisted topical delivery of photodynamically active mesoporous formulation for combination therapy of deep-Seated melanoma","volume":"12","author":"Tham","year":"2018","journal-title":"ACS Nano"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Alimardani, V., Abolmaali, S.S., Yousefi, G., Rahiminezhad, Z., Abedi, M., Tamaddon, A., and Ahadian, S. (2021). Microneedle arrays combined with nanomedicine approaches for transdermal delivery of therapeutics. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020181"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jconrel.2020.05.006","article-title":"Construction of microneedle-assisted co-delivery platform and its combining photodynamic\/immunotherapy","volume":"324","author":"Chen","year":"2020","journal-title":"J. Control. 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