Desenvolvimento de membranas eletrofiadas de poli (e-caprolactona) com oleorresina de copaíba (Copaifera sp) e nanopartículas de óxido de zinco (ZnO) para o tratamento avançado de lesões cutânea

Abstract

Lesões cutâneas representam um desafio significativo para a saúde pública, impulsionando a pesquisa em nanotecnologia para o desenvolvimento de curativos inovadores baseados em membranas eletrofiadas. Compostos naturais, como o oleorresina de copaíba (OC), atuam como promotores de agentes bioquímicos na proliferação e disseminação de substâncias vasoconstrutoras na fase inflamatória do processo de cicatrização, o uso de nanopartículas de óxido de zinco (ZnO) visa intensificar a atividade biomédica do sistema, promovendo uma melhoria na taxa de cicatrização da área lesionada. Dentro deste contexto, esta tese concentrou-se no desenvolvimento de membranas de poli (e-caprolactona) (PCL) com oleorresina de copaíba (OC) e nanopartículas de óxido de zinco (ZnO) visando o tratamento avançado de lesões cutâneas. Parâmetros adequados para a eletrofiação do PCL e o efeito das diferenteres frações mássicas de OC e ZnO na morfologia, propriedades físico-químicas, reológicas e biológicas foram investigadas. Fibras uniformes de PCL foram obtidas pela eletrofiação de uma solução de 10% de PCL, utilizando os seguintes parâmetros: tensão elétrica de 22 kV; distância agulha/coletor de 20 cm e vazão de 1 mL.h-1. A composição química do oleorresina de copaíba foi determinada, evidenciando a predominância de sesquiterpenos e análise reológica indicou que o OC apresenta comportamento newtoniano. A morfologia das membranas revelou que as fibras obtidas foram uniformes e aleatoriamente distribuídas e a adição de OC e ZnO aumentou o diâmetro das fibras em relação ao PCL. Análises térmicas, mecânicas e química indicaram uma modificação físico- química com a adição de OC e ZnO. A investigação do potencial zeta revelou uma carga superficial negativa nas membranas, indicando interações favoráveis para aplicações biomédicas. A presença de OC e ZnO promoveu o aumento da capacidade de intumescimento, um processo crucial para curativos avançados. As composições de PCL/OC apresentaram um grau de intumescimento superior a 100%, sendo a composição PCL/OC/ZnO-0,5 a que apresentou o maior valor de intumescimento médio, com 180% em 8 horas de experimento. A degradação in vitro revelou uma aceleração na perda de massa, influenciando a biodegradabilidade. A composição PCL/OC-15 apresentou uma perda de massa de 23%, enquanto as composições PCL/OC/ZnO-0,5 e PCL/OC/ZnO-1 apresentaram uma perda de massa de 30% em 56 dias. A capacidade antimicrobiana foi testada frente a Staphylococcus aureus (S. aureus) e Escherichia coli (E. coli). As membranas de composição PCL/OC apresentaram inibição de 99,9% contra S. aureus, enquanto a adição de ZnO nas composições PCL/OC/ZnO aumentou a capacidade antimicrobiana, apresentando inibição de 99,9% frente a S. aureus e E. coli. Testes de viabilidade celular, por meio do ensaio de MTT, evidenciaram a não toxicidade das membranas, indicando seu potencial em engenharia de tecidos e curativos de feridas. Este estudo contribui para o avanço de materiais biomédicos, destacando as promissoras propriedades das membranas de PCL/OC e PCL/OC/ZnO.

Abstract: Skin injuries represent a significant challenge for public health, driving research in nanotechnology for the development of innovative dressings based on electrospun membranes. Natural compounds such as copaiba oleoresin (CO) act as promoters of biochemical agents in the proliferation and dissemination of vasoconstrictive substances in the inflammatory phase of the healing process. The use of zinc oxide nanoparticles (ZnO) aims to enhance the biomedical activity of the system, promoting an improvement in the healing rate of the injured area. Within this context, this thesis focused on the development of poly(e-caprolactone) (PCL) membranes with copaiba oleoresin (CO) and zinc oxide nanoparticles (ZnO) for advanced treatment of skin lesions. Suitable parameters for PCL electrospinning and the effect of different mass fractions of CO and ZnO on the morphology, physicochemical, rheological, and biological properties were investigated. Uniform PCL fibers were obtained by electrospinning a 10% PCL solution using the following parameters: electric voltage of 22 kV; needle/collector distance of 20 cm, and flow rate of 1 mL.h-1. The chemical composition of copaiba oleoresin was determined, showing the predominance of sesquiterpenes, and rheological analysis indicated that CO exhibits Newtonian behavior. The morphology of the membranes revealed that the obtained fibers were uniform and randomly distributed, and the addition of CO and ZnO increased the diameter of the fibers compared to PCL. Thermal, mechanical, and chemical analyses indicated a physicochemical modification wSkin injuries represent a significant challenge for public health, driving research in nanotechnology for the development of innovative dressings based on electrospun membranes. Natural compounds such as copaiba oleoresin (CO) act as promoters of biochemical agents in the proliferation and dissemination of vasoconstrictive substances in the inflammatory phase of the healing process. The use of zinc oxide nanoparticles (ZnO) aims to enhance the biomedical activity of the system, promoting an improvement in the healing rate of the injured area. Within this context, this thesis focused on the development of poly(e-caprolactone) (PCL) membranes with copaiba oleoresin (CO) and zinc oxide nanoparticles (ZnO) for advanced treatment of skin lesions. Suitable parameters for PCL electrospinning and the effect of different mass fractions of CO and ZnO on the morphology, physicochemical, rheological, and biological properties were investigated. Uniform PCL fibers were obtained by electrospinning a 10% PCL solution using the following parameters: electric voltage of 22 kV; needle/collector distance of 20 cm, and flow rate of 1 mL.h-1. The chemical composition of cwas determined, showing the predominance of sesquiterpenes, and rheological analysis indicated that CO exhibits Newtonian behavior. The morphology of the membranes revealed that the obtained fibers were uniform and randomly distributed, and the addition of CO and ZnO increased the diameter of the fibers compared to PCL. Thermal, mechanical, and chemical analyses indicated a physicochemical modification with the addition of CO and ZnO. Zeta potential investigation revealed a negative surface charge on the membranes, indicating favorable interactions for biomedical applications. The presence of CO and ZnO promoted an increase in swelling capacity, a crucial process for advanced dressings. The PCL/CO compositions exhibited a swelling degree higher than 100%, with the PCL/CO/ZnO-0.5 composition showing the highest average swelling value, with 180% in 8 hours of experimentation. In vitro degradation revealed an acceleration in mass loss, influencing biodegradability. The PCL/CO-15 composition showed a mass loss of 23%, while the PCL/CO/ZnO-0.5 and PCL/CO/ZnO-1 compositions showed a mass loss of 30% in 56 days. Antimicrobial capacity was tested against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). PCL/CO membranes exhibited 99.9% inhibition against S. aureus, while the addition of ZnO in PCL/CO/ZnO compositions increased antimicrobial capacity, showing 99.9% inhibition against both S. aureus and E. coli. Cell viability tests, through the MTT assay, showed the non-toxicity of the membranes, indicating their potential in tissue engineering and wound dressings. This study contributes to the advancement of biomedical materials, highlighting the promising properties of PCL/CO and PCL/CO/ZnO membranes.ith the addition of CO and ZnO. Zeta potential investigation revealed a negative surface charge on the membranes, indicating favorable interactions for biomedical applications. The presence of CO and ZnO promoted an increase in swelling capacity, a crucial process for advanced dressings. The PCL/CO compositions exhibited a swelling degree higher than 100%, with the PCL/CO/ZnO-0.5 composition showing the highest average swelling value, with 180% in 8 hours of experimentation. In vitro degradation revealed an acceleration in mass loss, influencing biodegradability. The PCL/CO-15 composition showed a mass loss of 23%, while the PCL/CO/ZnO-0.5 and PCL/CO/ZnO-1 compositions showed a mass loss of 30% in 56 days. Antimicrobial capacity was tested against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). PCL/CO membranes exhibited 99.9% inhibition against S. aureus, while the addition of ZnO in PCL/CO/ZnO compositions increased antimicrobial capacity, showing 99.9% inhibition against both S. aureus and E. coli. Cell viability tests, through the MTT assay, showed the non-toxicity of the membranes, indicating their potential in tissue engineering and wound dressings. This study contributes to the advancement of biomedical materials, highlighting the promising properties of PCL/CO and PCL/CO/ZnO membranes.