TDF/FTC electrospun nanofibers for topical prevention of HIV transmission

Human immunodeficiency virus (HIV) is still a problem for global health so, there is a strong need to develop effective microbicides that can be used safely to protect from infection during sexual intercourse. This pre-exposure prophylaxis (PrEP) may be formulations containing oral or topical microbicides. Topical formulations have advantages as they are suitable for vaginal or rectal application and allow a higher local concentration of drug. It is recognized that the use of electrospun nanofibers for drug carriers is very promising in the biomedical field. So, the objective of this study is to develop a novel device for local application of antiretroviral microbicides enabling a controlled release of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), based on electrospun polymeric nanofibers. The aim of this study is to encapsulate TDF and FTC into electrospun polymeric nanofibers. Chosen polymers were polycaprolactone (PCL) and poly(vinyl alcohol) (PVA).info:eu-repo/semantics/submittedVersio

Desenvolvimento de nanofibras poliméricas microbicidas anti-VIH pela técnica de electrospinning

Dissertação de mestrado em Biofísica e BionanossistemasA infeção pelo vírus da imunodeficiência humana (VIH) provoca uma desregulação no sistema imunológico levando ao aparecimento de várias doenças oportunistas. Recorrendo a fármacos antirretrovirais, que inibem o processo de replicação do vírus, a infeção pode ser controlada e, deste modo, o paciente infetado pode não atingir a última fase da infeção pelo VIH, a Síndrome da Imunodeficiência Adquirida (SIDA). Também se pode recorrer a estes fármacos antirretrovirais para fazer uma profilaxia pré-exposição (PrEP) e assim prevenir a transmissão do VIH. Sendo as relações sexuais com parceiros de risco a principal via de transmissão do VIH, surge a necessidade de desenvolver uma estratégia para uma entrega local de fármacos antirretrovirais na vagina/reto. As nanofibras poliméricas, pelas suas caraterísticas morfológicas e pela facilidade na sua produção, são um sistema promissor para o carregamento e a libertação de fármacos na zona vaginal/anal. Esta dissertação teve como objetivo o desenvolvimento e o estudo de nanofibras poliméricas produzidas por electrospinning para uma aplicação vaginal/anal de modo a prevenir as infeções pelo VIH nas relações sexuais de risco. Desta forma, foram selecionados dois polímeros diferentes, a poli-caprolactona (PCL) e o poli-álcool vinílico (PVA) e em cada um deles foram incorporados dois fármacos antirretrovirais, o Tenofovir Disoproxil Fumarato (TDF) e a Emtricitabina (FTC). As propriedades físico-químicas das nanofibras produzidas foram caracterizadas por várias técnicas. Foi também feita uma avaliação do desempenho biofarmacêutico das nanofibras realizando ensaios de cinética de libertação dos fármacos, de mucoadesão e de citotoxicidade. Ambos os sistemas desenvolvidos demonstraram ser promissores para PrEP, permitindo incorporar facilmente grandes quantidades de fármacos bem como a sua libertação praticamente completa e rápida. As nanofibras de PCL apresentam como vantagem as suas características mecânicas que as tornam de mais fácil manuseamento, contudo as de PVA têm a vantagem de não ter de ser retiradas uma vez que se dissolvem em meio aquoso num curto espaço de tempo.The Human immunodeficiency virus (HIV) infection triggers a deregulation in the immune system, leading to the appearance of several opportunistic diseases. By using antiretroviral drugs, which inhibit the replication process of the virus, the infection can be controlled in a way that the infected patient may not reach the last phase of HIV infection, the Acquired Immunodeficiency Syndrome (AIDS). Antiretrovirals can also be used to do a pre-exposure prophylaxis (PrEP), preventing this way the transmission of HIV. Since sexual relations with risky partner is the main route of HIV transmission, a need arises to developed a strategy to applicate local antiretroviral drugs into the vagina / rectum. Due to their morphological characteristics and their easy production, polymeric nanofibers, are a promising approach for the release of drugs in the vaginal/anal zone. The aim of this dissertation is to assess and develop polymeric nanofibers, produced by electrospinning, with a vaginal/anal application in order to prevent the infection of HIV by sexual relations of risk. Two different polymers were chosen, polycaprolactone (PCL) and polyvinyl alcohol (PVA), and two antiretroviral drugs, Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC), that were incorporated into each one of the chosen polymers. The physic-chemical properties of nanofibers produced was characterized by various techniques. For an evaluation of the biopharmaceutical performance of the nanofibers were realized biological assays for drug release, mucoadhesion and cytotoxicity. Both developed systems have been shown to be promising for PrEP, allowing them not only to be incorporated in large quantities of drugs, but as well for an almost finished and rapid release for their practically complete and rapid. The advantage of PCL nanofibers is their easily handle mechanical characteristics, on the other end PVA have the advantage of not needing to be removed after applied, since they dissolve in aqueous medium in a short time

A Photo‐Thermoelectric Twist to Wireless Energy Transfer: Radial Flexible Thermoelectric Device Powered by a High‐Power Laser Beam

Abstract Systems for wireless energy transmission (WET) are gaining prominence nowadays. This work presents a WET system based on the photo‐thermoelectric effect. With an incident laser beam at λ = 1450 nm, a temperature gradient is generated in the radial flexible thermoelectric (TE) device, with a carbon‐based light collector in its center to enhance the photoheating. The three‐part prototype presents a unique approach by using a radial TE device with one simple manufacturing process ‐ screen‐printing. A TE ink with a polymeric matrix of poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate and doped‐Poly(vinyl alcohol) with Sb‐Bi‐Te microparticles is developed (S∽33 µVK −1 and s∽10.31 Sm −1 ), presenting mechanical and electrical stability. Regarding the device, a full electrical analysis is performed, and the influence of the light collector is investigated using thermal tests, spectrophotometry, and numerical simulations. A maximum output voltage (Vout) of ∽16 mV and maximum power density of ∽25 µWm −2 are achieved with Plaser = 2 W. Moreover, the device's viability under extreme conditions is explored. At T∽180 K, a 25% increase in Vout compared to room‐temperature conditions is achieved, and at low pressures (∽10 ‒6 Torr), an increase of 230% is obtained. Overall, this prototype allows the supply of energy at long distances and remote places, especially for space exploration

A photo‐thermoelectric twist to wireless energy transfer: radial flexible thermoelectric device powered by a high‐power laser beam

Systems for wireless energy transmission (WET) are gaining prominence nowadays. This work presents a WET system based on the photo-thermoelectric effect. With an incident laser beam at λ = 1450 nm, a temperature gradient is generated in the radial flexible thermoelectric (TE) device, with a carbon-based light collector in its center to enhance the photoheating. The three-part prototype presents a unique approach by using a radial TE device with one simple manufacturing process - screen-printing. A TE ink with a polymeric matrix of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate and doped-Poly(vinyl alcohol) with Sb-Bi-Te microparticles is developed (S∽33 µVK−1 and s∽10.31 Sm−1), presenting mechanical and electrical stability. Regarding the device, a full electrical analysis is performed, and the influence of the light collector is investigated using thermal tests, spectrophotometry, and numerical simulations. A maximum output voltage (Vout) of ∽16 mV and maximum power density of ∽25 µWm−2 are achieved with Plaser = 2 W. Moreover, the device's viability under extreme conditions is explored. At T∽180 K, a 25% increase in Vout compared to room-temperature conditions is achieved, and at low pressures (∽10‒6 Torr), an increase of 230% is obtained. Overall, this prototype allows the supply of energy at long distances and remote places, especially for space exploration.Federación Española de Enfermedades Raras | Ref. UID/NAN/50024/2019Federación Española de Enfermedades Raras | Ref. NORTE‐01‐0145‐FEDER022096Fundação para a Ciência e a Tecnologia | Ref. UIDB/04968/2020Fundação para a Ciência e a Tecnologia | Ref. UIDP/04968/202