Publicação
Development of a poly(L-Lactic acid) based drug release system
| Resumo: | Nanomedicine and controllable drug delivery systems have recently initiated their way into therapeutics. Faulty and, many times, ineffective approaches that conventional medicine uses need to be replaced by novel and smart materials that assure that a drug is delivered in the right place, at the right time. Polymeric materials are now widely used to produce drug delivery vehicles with tunable characteristics and, if needed, triggered releases. Although several polymeric materials are already being used to produce drug delivery systems it is, however, necessary to reach an active control of the drug release rate. Hence, the addition of a stimuli-sensitive component to the system that could trigger or increase the drug release rate would be of great interest. Therefore, during this work a polymeric platform containing a drug carrier (zeolite) and a stimuli-sensitive component (Terfenol-D) was developed. Firstly, a theoretical and experimental screening involving different zeolites with different characteristics (structure, crystal size, Si/Al ratio and counter ion) and loading methods with different solvents (hexane, ethanol and acetone) was performed in order to understand their influence in the loading of a model drug – Ibuprofen. Next, preparation of poly(L-lactic acid) membranes was optimized by testing three different polymer concentration. The membranes were prepared by freeze-drying method. Preliminary results from the molecular modelling studies indicated that faujasite and beta polymorph- A structures were the ones allowing a greater displacement of the drug inside the pores. Experimental trials indicated that hexane was the solvent providing greater loadings. From the tested zeolites, the nanosized faujasite (crystal size of ~250nm) was selected due to its complete drug release at 24h. Moreover, membranes prepared with 5(wt/vol.)% presented the best morphological and mechanical characteristics that were maintained after the incorporation of the zeolite and Terfenol-D particles. Comparing the four different drug release systems prepared (loaded zeolites; loaded membranes; membranes with loaded zeolites; and membranes with loaded zeolites and Terfenol-D under magnetic fields) it is clear that the systems present significant differences in the release kinetics and mechanisms. The membranes containing IBU-loaded zeolites appear to present a combination between the release of IBU-loaded membranes and the IBU-loaded zeolites. The release assays with the membranes containing loaded zeolite and Terfenol-D particles confirmed the influence of the applied magnetic fields in the release ratio. When the trigger is applied the Korsmeyer-Peppas model indicates a super case-II transport, indicating that the release of the drug is being driven mostly by a swelling or erosion mechanism, explained by the movement of the magnetostrictive particles when subject to the magnetic field. |
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| Autores principais: | Barbosa, João Alberto Cunha |
| Assunto: | Zeolites Poly(L-lactic acid) Molecular modelling Controlled release Magnetic stimuli Zeólitos Ácido poli(L-láctico) Modelação molecular Libertação controlada Estimulo magnético Ciências Naturais::Ciências Biológicas |
| Ano: | 2015 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Nanomedicine and controllable drug delivery systems have recently initiated their way into therapeutics. Faulty and, many times, ineffective approaches that conventional medicine uses need to be replaced by novel and smart materials that assure that a drug is delivered in the right place, at the right time. Polymeric materials are now widely used to produce drug delivery vehicles with tunable characteristics and, if needed, triggered releases. Although several polymeric materials are already being used to produce drug delivery systems it is, however, necessary to reach an active control of the drug release rate. Hence, the addition of a stimuli-sensitive component to the system that could trigger or increase the drug release rate would be of great interest. Therefore, during this work a polymeric platform containing a drug carrier (zeolite) and a stimuli-sensitive component (Terfenol-D) was developed. Firstly, a theoretical and experimental screening involving different zeolites with different characteristics (structure, crystal size, Si/Al ratio and counter ion) and loading methods with different solvents (hexane, ethanol and acetone) was performed in order to understand their influence in the loading of a model drug – Ibuprofen. Next, preparation of poly(L-lactic acid) membranes was optimized by testing three different polymer concentration. The membranes were prepared by freeze-drying method. Preliminary results from the molecular modelling studies indicated that faujasite and beta polymorph- A structures were the ones allowing a greater displacement of the drug inside the pores. Experimental trials indicated that hexane was the solvent providing greater loadings. From the tested zeolites, the nanosized faujasite (crystal size of ~250nm) was selected due to its complete drug release at 24h. Moreover, membranes prepared with 5(wt/vol.)% presented the best morphological and mechanical characteristics that were maintained after the incorporation of the zeolite and Terfenol-D particles. Comparing the four different drug release systems prepared (loaded zeolites; loaded membranes; membranes with loaded zeolites; and membranes with loaded zeolites and Terfenol-D under magnetic fields) it is clear that the systems present significant differences in the release kinetics and mechanisms. The membranes containing IBU-loaded zeolites appear to present a combination between the release of IBU-loaded membranes and the IBU-loaded zeolites. The release assays with the membranes containing loaded zeolite and Terfenol-D particles confirmed the influence of the applied magnetic fields in the release ratio. When the trigger is applied the Korsmeyer-Peppas model indicates a super case-II transport, indicating that the release of the drug is being driven mostly by a swelling or erosion mechanism, explained by the movement of the magnetostrictive particles when subject to the magnetic field. |
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