Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

Orientador: Jose Pedrazzoli Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T07:53:42Z (GMT). No. of bitstreams: 1 Fusaro_Claudio_M.pdf: 210087 bytes, checksum: 82412467f7edce8db8bce228762ae320 (MD5) Previous issue date: 2006 / Resumo: O transporte transdérmico de substâncias com o ultra-som terapêutico, método denominado fonoforese, oferece muitas vantagens quando comparado as outras vias de administração de drogas. O objetivo deste estudo foi verificar a influência do ultra-som na absorção de diclofenaco dietilamônio (Cataflam Emulgel®, Novartis) após fonoforese em voluntários sadios. Doze voluntários sadios foram submetidos à aplicação tópica de Cataflam Emulgel® em uma área de 150cm2 na região do dorso. No grupo controle os voluntários receberam a aplicação tópica sem emissão de ultra-som (sham) e o grupo teste recebeu a aplicação tópica através da fonoforese. A concentração plasmática de diclofenaco foi mensurada pelo HPLC (high perfomance liquid chromatography) durante um período de 8h após as aplicações. Neste trabalho demonstramos que a aplicação transdérmica de diclofenaco dietilamônio pela fonoforese, em uma única aplicação, não induz aumento da concentração plasmática quando comparada a aplicação sem ultra-som / Abstract: Transdermal drug delivery with therapeutic ultrasound, method called phonophoresis, offers many advantages when compared to other drug delivery methods. The aim of this study was to verify the influence of ultrasound on the transdermal delivery of diclofenac diethylammonium (Cataflam Emulgel®, Novartis) post phonophoresis in healthy volunteers. Twelve healthy human volunteers were submitted to topical application of Cataflam Emulgel® on 150cm2 area on the dorsum. In the Control Group, the volunteers received topical application with the ultrasound switched off and the Test Group received topical application by phonophoresis. The diclofenac plasma concentration was measured by high perfomance liquid chromatography (HPLC) during a period of 8h after dosing. We provided evidence that transdermal application of diclofenac diethylammonium by phonophoresis, in a single dose, has not induced plasmatic concentration increase when compared to topical application alone / Mestrado / Mestre em Farmacologia

Dans ce travail de thèse, nous avons préparées des émulsions de Pickering innovantes, stabilisées par des nanoparticules (NP) biocompatibles et biodégradables de poly (acide lactique-co-glycolique) (PLGA), en utilisant du Miglyol comme phase huileuse. Ces systèmes permettent de s’affranchir de l’ajout de tensioactifs synthétiques, utilisés pour stabiliser les émulsions classiques, et qui sont souvent à l’origine d’irritations lors de traitements topiques chroniques. Dans ces émulsions ont été co-encapsulées deux substances actives, la première, un agent immunosuppresseur, dans les NP PLGA, la seconde, un agent anti-inflammatoire, dans les gouttelettes de Miglyol.Dans un premier temps, une étude physicochimique approndie a permis de mieux comprendre les mécanismes de stabilisation de ces émulsions, en fonction du type de NP utilisé. Aussi, l’influence de l’ajout de substances actives a été évaluée sur les structures macroscopique, microscopique et interfaciale des émulsions, mais également sur leur stabilité. Dans un deuxième temps, nous avons démontré que l’ajout de Carbopol, un polymère épaississant, permettait d’améliorer la stabilité, la texture et le pH des émulsions. Enfin, le potentiel thérapeutique d’un tel système à été évalué de manière préliminaire, notamment sa cytotoxicité sur des cultures de kératinocytes, mais aussi son activité immunosuppressive sur des cellules immunitaires activées et leur production de cytokines. Un tel système peut donc s’avérer intéressant pour le traitement de pathologies cutanées chroniques. / In this thesis work, we formulated innovative Pickering emulsions, stabilized by biocompatible and biodegradable poly (lactic-co-glycolic acid) nanoparticles (NP), using Miglyol as the oil phase. These systems could be an alternative to conventional emulsions, often stabilized with synthetic surfactants that can be responsible for irritation in particular during long-term topical treatments. Two active pharmaceutical ingredients (API) were successfully co-encapsulated, the first one, an immunosuppressant agent, entrapped in PLGA NP, the second one, an anti-inflammatory agent, incorporated in Miglyol droplets.Firstly, a thorough physicochemical characterization allowed to better understand the stabilization mechanism of these emulsions, depending on the type of NP used. Moreover, the influence of the addition of API was evaluated on the macroscopic, microscopic and interfacial structures of the emulsions, also on their stability. Secondly, we demonstrated that the addition of Carbopol, a thickening agent, improved the stability, texture and pH of emulsions. Finally, the therapeutic potential of such system was investigated through preliminary evaluation of its cytotoxicity on keratinocyte cells, but also its immunosuppressive activity on activated immune cells and their cytokine production. Such a system could be interesting for the treatment of chronical skin diseases.

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Agradecemos a compreensão. on 2016-07-29T16:16:30Z (GMT) / Submitted by ALICE HADDAD DO PRADO null (alicehaddadp@gmail.com) on 2016-07-29T16:26:20Z No. of bitstreams: 1 Dissertação - Alice Haddad do Prado.pdf: 2329800 bytes, checksum: 60401746b6bc1cb494e5e3107ef17ec6 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-08-01T14:37:37Z (GMT) No. of bitstreams: 1 prado_ah_me_arafcf.pdf: 2329800 bytes, checksum: 60401746b6bc1cb494e5e3107ef17ec6 (MD5) / Made available in DSpace on 2016-08-01T14:37:37Z (GMT). No. of bitstreams: 1 prado_ah_me_arafcf.pdf: 2329800 bytes, checksum: 60401746b6bc1cb494e5e3107ef17ec6 (MD5) Previous issue date: 2016-05-24 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O p-metoxicinamato de octila (OMC) vem sendo empregado em protetores solares objetivando a prevenção do câncer de pele e envelhecimento precoce. Todavia, estudos têm detectado a presença deste filtro solar em amostras de sangue, urina e leite após sua administração cutânea. Para promover a retenção do OMC nas camadas mais externas da pele, bem como protegê-lo da fotodegradação, sua incorporação em carreador lipídico nanoestruturado (CLN) pode ser interessante, pois este sistema permite maior retenção cutânea do ativo e consequentemente menor permeação pela pele, além de maior proteção e encapsulação. O objetivo deste trabalho foi avaliar o potencial de CLN como estratégia para incorporação do OMC. Os CLNs foram compostos por: miristato de miristila (MM) como lipídeo sólido, triglicerídeo de ácido cáprico e caprílico (TACC) como lipídeo líquido e tween 80 (T80) como tensoativo (F1), associados ou não à fosfatidilcolina de soja (FS) – F2 ou óleo de rícino (OR) – F3. O OMC foi adicionado na fase lipídica na concentração de 1,0%, obtendo-se as formulações F1.OMC, F2.OMC e F3.OMC. A caracterização dos sistemas foi realizada a partir de análises de diâmetro médio, polidispersidade, potencial zeta, calorimetria diferencial exploratória, microscopia de força atômica e microscopia eletrônica de varredura. Foi realizada a eficiência de encapsulação das formulações, além de ensaios de determinação do fator de proteção solar (FPS), liberação, permeação, retenção cutânea e citotoxicidade in vitro. Também, foi desenvolvido um método analítico para a quantificação do OMC por cromatografia líquida de ultra eficiência (UPLC) com fase móvel constituída por 80:20 de acetonitrila e água ácida. As formulações desenvolvidas apresentaram valores de diâmetro hidrodinâmico médio entre 90 e 250 nm, índice de polidispersidade de 0,09 até 0,26 e potencial zeta de aproximadamente -20 mV. As análises de microscopia de força atômica e microscopia eletrônica de varredura sugeriram que as formulações apresentam formato esférico. Os resultados de DSC mostraram que os sistemas apresentaram estrutura cristalina, sofrendo alteração com a incorporação de OMC, além do aumento no ponto de fusão. Os resultados indicaram valores de FPS de aproximadamente 40 para as formulações. Os ensaios de liberação in vitro demonstraram que o OMC foi liberado das formulações seguindo o modelo matemático proposto por Peppas. A formulação F2.OMC foi a que promoveu maior liberação (55%) de OMC dos carreadores e maior permeação (37%) e retenção cutânea (0,17%). A formulação F1.OMC demonstrou menor liberação (30%) e retenção cutânea (0,05%) apresentando maior eficiência de encapsulação (60%), enquanto a formulação F3.OMC foi responsável pela menor permeação (18%). Os ensaios de citotoxicidade in vitro, empregando células HaCaT saudáveis, evidenciaram que as formulações não se apresentaram tóxicas na faixa de IC50 entre 0,08 e 0,004%. Os resultados sugerem que a formulação F3.OMC apresenta potencial aplicação para incorporação de OMC, objetivando sua aplicação em formulações fotoprotetoras. / The octyl methoxycinnamate has been used in sunscreens aiming at the prevention of skin cancer and premature aging. However, studies have detected the presence of this UV filter in samples of blood, urine and milk after topical administration. To promote the retention of the OMC in the outer layers of the skin and protect it from photobleaching, their incorporation into nanostructured lipid carrier (NLC) can be interesting because this system allows greater skin retention of active and therefore less permeation through the skin, besides greater protection and encapsulation. The objective of this study was to evaluate the potential of NLC as a strategy for incorporating the OMC. The NLCs was composed of: myristate miristila as solid lipid, acid triglyceride capric and caprylic as liquid lipid and tween 80 as surfactant (F1), associated or not with soy phosphatidylcholine (F2) or castor oil (F3). OMC was added to the lipid phase in a concentration of 1.0% to yield the F1.OMC, F2.OMC and F3.OMC formulations. The characterization of the systems was conducted from analysis of average diameter, polydispersity, zeta potential, differential scanning calorimetry (DSC), atomic force microscopy and scanning electron microscopy. The encapsulation efficiency of the formulations was carried out, as in vitro assays like sun protection fator (SPF), release, skin permeation, skin retention and cytotoxicity. Also, an analytical method was developed to quantify the OMC using liquid chromatography ultra-efficiency with mobile phase of 80:20 acetonitrile and acidic water. The formulations showed hydrodynamic mean diameter values between 90 and 250 nm, polydispersity of 0.09 to 0.26 and zeta potential of about - 20 mV. The analysis of atomic force microscopy and scanning electron microscopy suggested that the formulations have spherical shape. The DSC results showed that the systems suffering crystalline structure changes with the incorporation of OMC, besides the increase in melting point. The SPF results indicate values about 40 for all formulations. In vitro release tests showed that the OMC was released from formulations following the mathematical model proposed by Peppas. The formulation F2.OMC was that promoted the greatest release of OMC (55%) higher skin permeation (37%) and retention (0.17%). The F1.OMC showed lower release (30%), skin retention (0.05%) and higher encapsulation efficiency (60%), while the F3.OMC formulation was responsible for the lower skin permeation (18%). In vitro cytotoxicity assays employing healthy HaCaT cells, demonstrated that the formulations did not show toxic IC50 in the range between 0.08 and 0.004%. The results suggest that F3.OMC formulation has potential application for incorporation of OMC, aiming their use in sunscreens formulations. / FAPESP: 2014/22426-2

Orofacial pain, although it is a problem that affects the quality of life of millions of people, is still poorly understood and, consequently, its treatment are difficult to predict. This treatment usually involves systemic pharmacotherapy, in most cases, it is accompanied by various side effects. Thus, the present study aimed to evaluate the pharmacological effect of topical application of a gel containing carvacrol on liposomes induced orofacial nociception in mice. First, we performed the test orofacial nociception induced by administration of 2% formalin into the upper lip of mice and then this tissue was removed for measuring the activity of myeloperoxidase (MPO). In the test described above, applying the carbopol gel (control group) or gel with liposomes containing carvacrol (1% and 5%) were performed 1 h before the induction of nociceptive orofacial; reference drug (diclofenac diethylammonium in gel form) was administered 2 hours before the induction of nociception. It was observed that at a concentration of 1%, the gel containing liposomes with carvacrol reduced the nociceptive behavior of scratching the orofacial region (34.4 ± 4.6 s, p <0.05) compared to the control group (74.1 s ± 4.6, p <0.05) is equivalent to the reduction observed in the group that was used reference drug (diclofenac diethylammonium gel - 34.0 ± 7.3 s, p <0.05). The gel 1% carvacrol was also able to reduce the activity of the enzyme MPO (0.7 ± 0.1 UMPO / mg tissue, p <0.05) compared to the control group (2.0 ± 0.3 UMPO / mg tissue, p <0.05) and behaved similarly to diclofenac diethylammonium group gel (0.5 ± 0.2 UMPO / mg tissue, p <0.05). Thus, it is concluded that the carvacrol gel containing liposomes at a concentration of 1% was effective in the control of nociception induced by formalin and had an important effect on cell migration at low concentrations suggesting that the gel containing liposomes has an effect carvacrol topic in the therapy of painful processes associated with orofacial region. However, such phenomena were not observed at 5% concentration. / A dor orofacial, embora seja um problema que prejudica a qualidade de vida de milhões de pessoas, ainda é pouco compreendida e, consequentemente, seu tratamento é de difícil prognóstico. Este tratamento normalmente envolve farmacoterapia sistêmica que, na maioria das vezes, vem acompanhada de diversos efeitos colaterais. Desta forma, o presente estudo visou avaliar farmacologicamente o efeito da aplicação tópica de um gel contendo lipossomas com carvacrol sobre a nocicepção orofacial induzida em camundongos. Primeiramente, foi realizado o teste de nocicepção orofacial induzido pela administração de formalina 2% em lábio superior de camundongos e em seguida este tecido foi removido para a mensuração da atividade da enzima mieloperoxidase (MPO). No teste acima descrito, a aplicação do gel de carbopol (grupo controle), ou gel contendo lipossomas com carvacrol (1% e 5%) foram realizados 1 h antes da indução da nocicepção orofacial; a droga referência (diclofenaco dietilamônio na forma farmacêutica de gel) foi aplicada 2 h antes da indução da nocicepção. Foi observado que, na concentração de 1%, o gel contendo lipossomas com carvacrol reduziu o comportamento nociceptivo de coçar a região orofacial (34,4 ± 4,6 s, p < 0,05) em relação ao grupo controle (74,1 ± 4,6 s, p < 0,05) sendo equivalente à redução observada no grupo em que foi utilizada a droga de referência (diclofenaco dietilamônio gel - 34,0 ± 7,3 s, p < 0,05). O gel de carvacrol a 1% também foi capaz de reduzir a atividade da enzima MPO (0,7 ± 0,1 UMPO / mg de tecido, p < 0,05) em relação ao grupo controle (2,0 ± 0,3 UMPO / mg de tecido, p < 0,05) e se comportou de forma semelhante ao grupo do diclofenaco dietilamonio gel (0,5 ± 0,2 UMPO / mg de tecido, p < 0,05). Dessa forma, conclui-se que o gel contendo lipossomas com carvacrol na concentração de 1% foi eficaz no controle da nocicepção induzida por formalina e teve importante efeito sobre a migração celular, sugerindo que em baixas concentrações o gel contendo lipossomas com carvacrol tem um efeito tópico na terapia de processos dolorosos associados à região orofacial. No entanto, não foram observados tais fenômenos na concentração de 5%.

Cannabidiol, a non-psychoactive constituent of cannabis, has garnered much attention after United States Food and Drug Administration approved Epidiolex® for oral use. Although therapeutic effect of cannabidiol after systemic absorption has been investigated extensively, its therapeutic potential in treating skin disorders after local delivery still needs further exploration. Our study has investigated the effect of cannabidiol concentration, chemical enhancers, and essential oils on percutaneous absorption of cannabidiol. In vitro permeation tests were conducted on human skin. The 24 h study results suggest no significant difference in amount of drug absorbed into skin, between 5% (242.41 ± 12.17 µg/cm) and 10% (232.79 ± 20.82 cm) cannabidiol solutions. However, 1% delivered (23.02 ± 4.74 µg/cm) significantly lower amount of drug into skin than 5% and 10%. Transcutol and isopropyl myristate did not enhance delivery of cannabidiol. However, oleic acid was found to be useful as chemical enhancer. Oleic acid (43.07 ± 10.11 µg/cm) had significantly higher cannabidiol delivery into skin than the group without oleic acid (10.98 ± 3.40 µg/cm) after a 4 h in vitro permeation study. Essential oils at concentrations tested had lower total cannabidiol delivery when compared to control. This study's findings will help guide future research on the pharmacological effect of percutaneously delivered cannabidiol on inflammatory skin disorders.

Hypothèse: L’impression sur textile d’une formulation de microparticules lipidiques avec un principe actif (éconazole nitrate) permet de conserver ou d’améliorer son activité pharmaceutique ex vivo et in vitro. Méthode: Une formulation de microparticules d’éconazole nitrate (ECN) a été formulée par homogénéisation à haut cisaillement, puis imprimée sur un textile LayaTM par une méthode de sérigraphie. La taille des microparticules, la température de fusion des microparticules sur textile et la teneur en éconazole du tissu ont été déterminées. La stabilité de la formulation a été suivie pendant 4 mois à 25°C avec 65% humidité résiduelle (RH). L’activité in vitro des textiles pharmaceutiques a été mesurée et comparée à la formulation commerciale 1% éconazole nitrate (w/w) sur plusieurs espèces de champignons dont le C. albicans, C. glabrata, C. kefyr, C. luminisitae, T. mentagrophytes et T. rubrum. La thermosensibilité des formulations a été étudiée par des tests de diffusion in vitro en cellules de Franz. L’absorption cutanée de l’éconazole a été évaluée ex vivo sur la peau de cochon. Résultats: Les microparticules d’éconazole avaient des tailles de 3.5±0.1 μm. La température de fusion était de 34.8°C. La thermosensibilité a été déterminée par un relargage deux fois supérieur à 32°C comparés à 22°C sur 6 heures. Les textiles ont présenté une teneur stable pendant 4 mois. Les textiles d’ECN in vitro ont démontré une activité similaire à la formulation commerciale sur toutes ii espèces de Candida testées, ainsi qu’une bonne activité contre les dermatophytes. La diffusion sur peau de cochon a démontré une accumulation supérieure dans le stratum corneum de la formulation textile par rapport à la formulation Pevaryl® à 1% ECN. La thermo-sensibilité de la formulation a permis un relargage sélectif au contact de la peau, tout en assurant une bonne conservation à température ambiante. / Hypothesis: Textile imprinted with a formulation of microparticles of a drug (econazole nitrate) can maintain or improve its pharmaceutical activity ex vivo and in vitro. Methods: A formulation of econazole nitrate microparticles was made by high shear homogenization then printed on a LayaTM textile by screen-printing. The size of microparticles, melting temperature of microparticles on textile and econazole nitrate content were determined. The stability of the formulation was followed for 4 months at 25°C with 65% residual humidity (RH). The in vitro activity of pharmaceutical textiles was measured and compared to the commercial formulation econazole nitrate 1% (w/w) in several species of fungi including C. albicans, C. glabrata, C. kefyr, C. luminisitae, T. mentagrophytes and T. rubrum. Temperature sensitivity of the formulations was studied by in vitro tests in Franz diffusion cells. Dermal absorption of econazole nitrate was assessed ex vivo on pig skin. Results: Econazole microparticles were 3.5±0.1 μm in diameter. The melting temperature was 34.8°C. The thermosensitivity of the system was determined by a release test at 32°C compared to 22°C over 6 hours. Textiles showed stable levels for 4 months (97±0.3 μg/cm2). ECN textiles on in vitro tests showed similar activity to the commercial formulation on all Candida species tested, as well as good activity against dermatophytes. Ex vivo tests on pig skin showed a higher accumulation of ECN on the stratum corneum for textile formulation as compared to the Pevaryl® iv formulation. The thermo-sensitivity of the formulation permits a selective release in contact with the skin, while ensuring good storage at room temperature.

Pacientes vítimas de queimaduras convivem com seqüelas que podem diminuir sua auto-estima e qualidade de vida. Vítimas de queimaduras faciais são excluídos social e profissionalmente solicitando ao cirurgião plástico tratamentos complementares aos cirúrgicos para melhoria da aparência e qualidade da pele. Quinze pacientes do sexo feminino, vítimas de queimadura facial por álcool com mais de dois anos de evolução, foram submetidas a tratamento tópico com tretinoína 0,05% durante um ano, com exceção da região pré-auricular. Após este período, duas biópsias faciais, uma na região pré-auricular e outra um centímetro abaixo do lóbulo da orelha, foram realizadas para comparar áreas não tratadas e tratadas. Os fragmentos biopsiados foram submetidos à análise mecânica e histológica. Medidas de resistência e elastância foram significativamente menores nas áreas tratadas (resistência p=0,03 e elastância p<0,05). Não houve diferença estatística entre as densidades de fibras colágenas totais e de colágeno tipo III, fibras elásticas e versicam nas áreas tratadas e não tratadas / Patients that are victims of burns live with sequelae that may decrease their self-esteem and quality of life. Victims of facial burns are excluded from social and professional life. They request the plastic surgeon to provide complementary treatment to the surgical one, so as to improve their appearance and the quality of the skin. Fifteen female patients, victims of facial burns caused by alcohol with more than two years of evolution, underwent topical treatment with 0.05% tretinoin during one year. During this period, a small area at the pre-auricular region was spared from the treatment. After this period two facial biopsies, one in the pre-auricular area and the other one, 1 cm below the ear lobe, were performed to compare treated and non treated areas. Skin strips underwent a mechanical and histological analysis. Measurements of resistance and elasticity were significantly lower in the treated skin as compared with non-treated skin (resistance, p=0.03 and elasticity, p<0.05). The density of collagen and collagen type III fibers, elastic fibers and versican was not significantly different between treated and non-treated skins