Publicação
Development of polymeric nanoparticles by microfluidic technologies as functional drug delivery devices
| Resumo: | Nanoparticles (NPs) are entities with dimensions ranging from 1 and 100 nanometers (nm) in size. As a result of their narrow dimension, NPs exhibit a large surface area-to-volume ratio compared to bulk material, which lead to improved properties. Indeed, NPs have been widely explored in different research fields, demonstrating a strong potential in nanomedicine as drug delivery systems. However, their performance is strictly related to their physicochemical characteristics. Among the different parameters that can be tuned in the resulting NPs, the size stands out for its key role in determining NPs fate, biodistribution, cell interaction and resulting biological effects. However, the ability to produce NPs with precise and defined sizes remains a challenge for the most common and traditional synthesis techniques. Polymeric NPs are mainly synthesized through the nanoprecipitation process. This reaction leads to the production of NPs through the nucleation of the individual polymer chains until their growth into the final entities. During this process, one of the main factors that affects the resulting product size is the mixing of the organic and the aqueous phase. Indeed, the mixing guides the diffusion process between the two miscible phases and, consequently, the formation of NPs. To achieve high mixing performances, the work herein presented leverages microfluidic technology to obtain NPs with a defined size. Indeed, microfluidics allow to investigate the behavior of fluids flowing through microscale channels and can be efficiently applied to NPs production. At first, we assessed the impact of several experimental parameters (polymer concentration, flow rates, and flow rate ratio between the aqueous and organic solutions) on the resulting NPs features, in particular their size. Then, three sizes of interest were selected (30, 50 and 70 nm) to investigate the role of the NPs size on drug delivery and biological effects. Additionally, it was explored the NPs size influence on their ability for biological barriers crossing, as well as cellular internalization and trafficking. The employed micromixer also revealed being a powerful platform for the handling of high molecular weight polymers. Indeed, the synthesis of chitosan-hyaluronic acid NPs was successfully carried out by the microfluidic chip, leading to smaller NPs compared to the conventional method (dropwise). The data herein reported indicates that the NPs size can have a significant impact in their pharmacokinetics and cells response, suggesting that the precise control of NPs features can tailor the delivery of bioactive agents and enhance their biological efficacy. |
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| Autores principais: | Gimondi, Sara |
| Assunto: | Microfluidics Biodegradable polymers Nanoparticles size Controlled delivery Nanoparticles-cell interaction Microfluídica Polímeros biodegradáveis Tamanho das nanopartículas Libertação controlada Interação nanopartículas-célula |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Nanoparticles (NPs) are entities with dimensions ranging from 1 and 100 nanometers (nm) in size. As a result of their narrow dimension, NPs exhibit a large surface area-to-volume ratio compared to bulk material, which lead to improved properties. Indeed, NPs have been widely explored in different research fields, demonstrating a strong potential in nanomedicine as drug delivery systems. However, their performance is strictly related to their physicochemical characteristics. Among the different parameters that can be tuned in the resulting NPs, the size stands out for its key role in determining NPs fate, biodistribution, cell interaction and resulting biological effects. However, the ability to produce NPs with precise and defined sizes remains a challenge for the most common and traditional synthesis techniques. Polymeric NPs are mainly synthesized through the nanoprecipitation process. This reaction leads to the production of NPs through the nucleation of the individual polymer chains until their growth into the final entities. During this process, one of the main factors that affects the resulting product size is the mixing of the organic and the aqueous phase. Indeed, the mixing guides the diffusion process between the two miscible phases and, consequently, the formation of NPs. To achieve high mixing performances, the work herein presented leverages microfluidic technology to obtain NPs with a defined size. Indeed, microfluidics allow to investigate the behavior of fluids flowing through microscale channels and can be efficiently applied to NPs production. At first, we assessed the impact of several experimental parameters (polymer concentration, flow rates, and flow rate ratio between the aqueous and organic solutions) on the resulting NPs features, in particular their size. Then, three sizes of interest were selected (30, 50 and 70 nm) to investigate the role of the NPs size on drug delivery and biological effects. Additionally, it was explored the NPs size influence on their ability for biological barriers crossing, as well as cellular internalization and trafficking. The employed micromixer also revealed being a powerful platform for the handling of high molecular weight polymers. Indeed, the synthesis of chitosan-hyaluronic acid NPs was successfully carried out by the microfluidic chip, leading to smaller NPs compared to the conventional method (dropwise). The data herein reported indicates that the NPs size can have a significant impact in their pharmacokinetics and cells response, suggesting that the precise control of NPs features can tailor the delivery of bioactive agents and enhance their biological efficacy. |
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