Microemulsions Improve Topical Protoporphyrin IX (PpIX) Delivery for Photodynamic Therapy of Skin Cancer
DOI:
https://doi.org/10.1590/s2175-97902023e21920%20%20Keywords:
Protoporphyrin IX, Photodynamic therapy, Skin cancer, Microemulsion, In vitro skin retentionAbstract
We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodynamic Therapy (PDT) of skin cancers. Selected MEs consisting of Oil/Water (O/W) bicontinuous (BC) and Water/Oil (W/O) preparations were characterized as to pH, nanometric size, zeta potential, drug content, and viscosity. Sustained in vitro PpIX release was achieved from MEs 2A (O/W), 10B (BC) and 16B (W/O) through an artificial membrane for up to 24 h, characterizing MEs as drug delivery systems. None of these MEs showed permeation through the skin, demonstrating the required topical effect. After 4 h, in vitro retention of PpIX in the stratum corneum (SC) was higher from both ME 10B and control (PpIX at 60 µg/mL in PEG 300). However, in the Epidermis + Dermis ([Ep + D]), retention from ME 10B and ME 16B was ~40 times higher compared to control. Confocal Laser Scanning Microscopy (CLSM) showed higher fluorescence intensity in the SC for both control and ME 10B, whereas ME 10B fluorescence was higher in [Ep+D]. The results indicate that ME 10B is suitable for PpIX encapsulation, showing good characteristics and a localized effect for a potential delivery system for PDT-associated treatments of skin cancers.
Downloads
References
Agrawal OP, Agrawal S. An overview of new drug delivery system: microemulsion. Asian J Pharm Sci Tech. 2012;2(1):5-12.
Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Acta Derm Vener. 2013;93(3):261-269.
Almeida EDP, Dipieri LV, Rossetti FC, Marchetti JM, Bentley MVL, Nunes RDS, et al. Skin permeation, biocompatibility, and antitumor effect of chloroaluminum phthalocyanine associated to oleic acid in lipid nanoparticles. Photodiagn Photodyn Ther. 2018;2:262-273.
Apolinário AC, Salata GC, Bianco AF, Fukumori C, Lopes LB. Abrindo a caixa de pandora dos nanomedicamentos: há realmente muito mais espaço lá embaixo. Quim Nova. 2020;(43):212-225.
Baroli B, López-Quintela MA, Delgado-Charro MB, Fadda AM, Blanco-Méndez J. Microemulsions for topical delivery of 8-methoxsalen. J Controlled Release. 2000;69(1):209-218.
Basoglu H , Bilgin MD, Demir, MM. Protoporphyrin IX-loaded magnetoliposomes as a potential drug delivery system for photodynamic therapy: fabrication, characterization, and in vitro study. Photodiagn Photodyn Ther . 2016;13:81-90.
Bhattacharjee S. DLS and zeta potential-what they are and what they are not? J Controlled Release . 2016;235:337-351.
Bedin AC. Nanoemulsões contendo benzoilmetronidazol: desenvolvimento, caracterização e estudo de liberação in vitro. [dissertação]. Santa Catarina: Universidade Federal de Santa Catarina, 2011.
Bonnet, R. Photosensitizers of porphyrins and phthalocianine series for photodynamic therapy. Chem Soc Rev. 1995;24:19-33.
Calixto GMF, Bernegossi J, De Freitas LM, Fontana CR, Chorilli M. Nanotechnology-Based drug delivery systems for photodynamic Therapy of Cancer: A review. Molecules. 2016;(21):342.
Carollo ARH. Influência do ácido oléico como promotor de absorção cutânea para o ácido 5-aminolevulínico na terapia fotodinâmica do câncer de pele: estudos in vitro e in vivo em modelo animal. [dissertação]. São Paulo: Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto; 2007.
Chauhan LALIT, Muzaffar FAIZI, Lohia SARITA. Design, development and evaluation of topical microemulsion. Int J Pharm Pharm Sci. 2013;5(2):604-610.
Dabhi MR, Nagori SA, Sheth NR, Patel NK, Dudhrejiya AV. Formulation optimization of topical gel formulation containing micro-emulsion of terbinafine hydrochloride with simplex lattice design. Micro Nanosyst. 2011;3(1):1-7.
Damasceno BPGL, Silva JA, Oliveira EE, Silveira W, Araújo IB, Oliveira AGD. Microemulsão: um promissor carreador para moléculas insolúveis. Rev Cienc Farm Basica Apl. 2011;32(1):9-18.
Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2),57.
Da Silva CL, Del Ciampo JO, Rossetti FC, Bentley MVL, Pierre MBR. Improved in vitro and in vivo cutaneous delivery of protoporphyrin IX from PLGA-based nanoparticles. Photochem Photobiol. 2013;89(5):1176-1184.
De Campos Araújo, LMP. Dendrímeros como carreadores da protoporfirina IX para a terapia fotodinâmica tópica do câncer de pele. (Tese de doutorado) Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto; 2010.
De Campos Araújo LMP, Thomazine JA, Lopez, RFV. Development of microemulsions to topically deliver 5-aminolevulinic acid in photodynamic therapy. Eur J Pharm Biopharm. 2010;75(1):48-55.
Deda DK, Araki K. Nanotechnology, Light and chemical action: an effective combination to kill cancer cells. J Braz Chem Soc. 2015;26(12):2448-2470.
de Oliveira Miguel J, da Silva DB, da Silva GCC, Corrêa RJ, de Oliveira Miguel NC, Lione VDOF, et al. Polymeric nanoparticles favor the in vitro dermal accumulation of Protoporphyrin IX (PpIX) with optimal biocompatibility and cellular recovery in culture of healthy dermal fibroblasts after Photodynamic Therapy. J Photochem Photobiol A. 2020;386:112109.
da Silva DB, da Silva CL, Davanzo NN, da Silva Souza R, Correa RJ, Tedesco AC, et al. Protoporphyrin IX (PpIX) loaded PLGA nanoparticles for topical Photodynamic Therapy of melanoma cells. Photodiagn Photodyn Ther . 2021;35:102317.
Dögnitz, N, Salomon D, Zellweger M, Ballini JP, Gabrecht T, Lange N, et al. Comparison of ALA-and ALA hexyl-ester-induced PpIX depth distribution in human skin carcinoma. J Photochem Photobiol B: Biol. 2008;93(3):140-148.
Donnelly RF, McCarron PA, Woolfson AD. Drug delivery of aminolevulinic acid from topical formulations intended for photodynamic therapy. Photochem Photobiol . 2005;81(4):750-767.
El Maghraby GM. Transdermal delivery of hydrocortisone from eucalyptus oil microemulsion: effects of cosurfactants. Int J Pharm. 2008;355(1-2):285-292.
Fanun M. Microemulsions as delivery systems. Curr Opin Colloid Interface Sci. 2012;17(5):306-313.
Formariz TP, Urban MCC, Silva Júnior AAD, Gremião MPD, Oliveira, AGD. Microemulsões e fases líquidas cristalinas como sistemas de liberação de fármacos. Rev Bras Cienc Farm. 2005;41(3):301-313.
Harrison SM, Barry BW, Dugard PH. Effect of freezing on human skin permeability. J Pharm Pharmacol. 1984;(35):261-262.
Hathout RM, Mansour S, Mortada ND, Geneidi AS, Guy RH. Uptake of microemulsion components into the stratum corneum and their molecular effects on skin barrier function. Mol Pharm. 2010;7(4):1266-1273.
INCA-Instituto Nacional do Câncer -. Câncer de pele não melanoma [citado 2022 Abril 26]. Available from: Available from: https://www.inca.gov.br/tipos-de-cancer/cancer-de-pele-nao-melanoma
» https://www.inca.gov.br/tipos-de-cancer/cancer-de-pele-nao-melanoma
Kaur G, Mehta SK. Developments of Polysorbate (Tween) based microemulsions: Preclinical drug delivery, toxicity and antimicrobial application. Int J Pharm . 2017;529(1-2):134-160.
Khanna S, Katare OP, Drabu S. Lecithinised microemulsions for topical delivery of tretinoin. Int J Drug Dev Res. 2010;2(4):711-9.
Kloek J, Akkermans W, Van Henegouwen GMJB. Derivatives of 5-aminolevulinic acid for photodynamic therapy: enzymatic conversion into protoporphyrin. Photochem Photobiol . 1998;67(1):150-154.
Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci. 2006;(123):369-385.
Kreilgaard, M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv Rev. 2002;54(Suppl 1):S77-S98.
Lopes LB. Overcoming the cutaneous barrier with microemulsions. Pharmaceutics . 2014;6(1):52-77.
McLoone N, Donnelly RF, McCarron PA, Walsh M, McKenna K. Aminolevulinic acid penetration into nodular basal cell carcinomas: influence of different concentrations and application times on amounts of ala delivered via a bioadhesive patch. Clin Photodyn. 2004;1:5-6.
Nastiti CM, Ponto T, Abd E, Grice JE, Benson HA, Roberts MS. Topical nano and microemulsions for skin delivery. Pharmaceutics . 2017;9(4):37.
Patel MR, Patel RB, Parikh JR, Solanki AB, Patel BG. Investigating effect of microemulsion components: in vitro permeation of ketoconazole. Pharm Dev Technol. 2011;16(3):250-8.
Patzelt A, Lademann J, Richter H, Darvin ME, Schanzer S, Thiede G, et al. In vivo investigations on the penetration of various oils and their influence on the skin barrier. Skin Res Technol. 2012;18(3):364-369.
Pierre MBR, Ricci E, Tedesco AC, Bentley MVLB. Oleic acid as optimizer of the skin delivery of 5-aminolevulinic acid in photodynamic therapy. Pharm Res. 2006;23(2):360-366.
Raza K, Negi P, Takyar S, Shukla A, Amarji B, Katare OP. Novel dithranol phospholipid microemulsion for topical application: development, characterization and percutaneous absorption studies. J Microencapsul. 2011;28(3):190-9.
Qidwai A, Nabi B, Kotta S, Narang JK, Baboota S, Ali J. Role of nanocarriers in photodynamic therapy. Photodiagn Photodyn Ther. 2020;30:101782.
Quiñones OG, Mata dos Santos HA, Kibwila DM, Leitao A, dos Santos Pyrrho A, Pádula MD, et al. In vitro and in vivo influence of penetration enhancers in the topical application of celecoxib. Drug Dev Ind Pharm. 2014;40(9):1180-1189.
Rossetti FC, Depieri LV, Tedesco AC, Bentley MVLB. Fluorometric quantification of protoporphyrin IX in porcine skin and phosphate buffer samples from in vitro penetration/ permeation studies. Braz J Pharm Sci. 2010;46(4):753-760.
Rossetti FC, Depieri LV, Bentley MVLB. Confocal laser scanning microscopy as a tool for the investigation of skin drug delivery systems and diagnosis of skin disorders. Confocal laser microscopy-principles and applications in medicine, biology, and the food sciences. 2013;99-140.
Rossetti FC, Depieri L, Praça FG, Del Ciampo JO, Fantini MC, Pierre MBR, et al. Optimization of protoporphyrin IX skin delivery for topical photodynamic therapy: nanodispersions of liquid-crystalline phase as nanocarriers. Eur J Pharm Sci. 2016;83:99-108.
Rossi CGFT, Dantas TDC, Neto AAD, Maciel MAM. Microemulsões: uma abordagem básica e perspectivas para aplicabilidade industrial. Rev Univ Rural Ser Cienc Exatas Terra. 2007;26(1-2):45-66.
Silva JAD, Apolinário AC, Souza MSR, Damasceno BDL, Medeiros ACD. Administração cutânea de fármacos: desafios e estratégias para o desenvolvimento de formulações transdérmicas. Rev Cienc Farm Basica Apl. 2010;31(3):125-131.
Singh Y, Meher JG, Raval K, Khan FA, Chaurasia M, Jain NK, et al. Nanoemulsion: Concepts, development, and applications in drug delivery. J Control Rel. 2017;252:28-49.
Wachowska M, Muchowicz A, Firczuk M, Gabrysiak M, Winiarska M, Wańczyk M. Aminolevulinic acid (ALA) as a prodrug in photodynamic therapy of cancer. Molecules. 2011;16(5):4140-4164.
Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2012;(64):128-137.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on-line journal has open and free access.
