Título:	Combinação de nanocarreadores lipídicos e métodos físicos para retenção de propionato de clobetasol em folículos pilosos
Autor(es):	Damasceno, Tamara Ângelo de Oliveira Santos
Orientador(es):	Gratieri, Taís
Coorientador(es):	Cunha Filho, Marcílio Sérgio Soares da Schneider, Marc
Assunto:	Nanotecnologia Nanopartículas lipídicas Folículos Dermatologia Farmacologia
Data de publicação:	12-Dez-2019
Data de defesa:	20-Dez-2018
Referência:	DAMASCENO, Tamara Ângelo de Oliveira Santos. Combinação de nanocarreadores lipídicos e métodos físicos para retenção de propionato de clobetasol em folículos pilosos. 2018. viii, 117 f., il. Tese (Doutorado em Ciências Farmacêuticas)—Universidade de Brasília, Brasília, 2018.
Abstract:	Clobetasol propionate (CLO) is a glucocorticoid used to treat several dermatological diseases such as eczema and psoriasis. Recent studies suggest its application also to inflammatory-caused scalp and hair disorders. In such conditions hair follicles (HF) are not only target site, but also can act as drug reservoirs. Therefore, a treatment capable to provide a specific drug delivery into the HF could result in higher effectiveness and safety when compared to oral or traditional topical medications. One of the strategies for HF targeting is the use of formulations containing lipid-based nanoparticles. Another promising approach is the application of physical methods for penetration enhancement. The aim of this study was to develop a nanosystem and observe the efficacy of combining different techniques to increase CLO retention in the HF. Nanostructured lipid carriers (NLC) were produced with CLO 0.05%. Particles were characterized in terms of size, PdI, zeta potential, stability and TEWL effect. Drug release experiments and in vitro skin permeation were conducted using Franz diffusion cells. Drug penetration in different skin layers was evaluated after passive NLC application and after the use of infrared irradiation (IR), ultrasound (US) or massage. Differential tape stripping recovered CLO from stratum corneum (SC), HF and remaining skin (RS) and the drug was further quantified by a validated HPLCUV method. NLC containing fluorescent dye were produced and their cutaneous penetration was observed by confocal microscopy. Obtained NLC presented sizes around 180 nm, with PdI below 0.2 and negative zeta potential. The formulation presented stability for 30 days under refrigeration and did not show any harm in TEWL tests. Particles demonstrated sustained drug release for more than 3 days. NLC were capable of increase CLO follicular retention about 4.5 times compared to CLO hydroalcoholic solution. In comparison to a commercial cream, these values reached about 40 times. Confocal images confirmed NLC favoured follicular delivery. NLC application followed by IR showed no benefit in terms of drug delivery. After US treatment, CLO retention increased for both HF and RS, compared to passive NLC exposition. Use of massage resulted in more than double the amount of CLO in the HF in relation to NLC passive application. CLO was not observed in the acceptor medium for any of the performed treatments, indicating that the drug was retained in the skin layers. The developed formulation showed great potential for delivering CLO to HF. The combination of NLC application with massage seems to be a good approach to enhance CLO follicular retention. The use of the presented strategies could enable the reduction of dose and frequency of drug application resulting in increased safety and efficacy for the patients.
Unidade Acadêmica:	Faculdade de Ciências da Saúde (FS) Departamento de Farmácia (FS FAR)
Informações adicionais:	Tese (doutorado)—Universidade de Brasília, Faculdade de Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, 2018.
Programa de pós-graduação:	Programa de Pós-Graduação em Ciências Farmacêuticas
Agência financiadora:	Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Aparece nas coleções:	Teses, dissertações e produtos pós-doutorado

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