Publicação
Development of pH-sensitive polymeric nanoparticles for targeted drug delivery to the ischemic heart
| Resumo: | Heart failure post-myocardial infarction remains one of the global leading causes of mortality. The therapeutics, available today, only ameliorate the symptoms, without having any preventive effect on the, functional and structural, heart-remodeling process that ensues after such ischemic event. For this, lately, nanotechnology has emerged as a possible alternative to overcome countless limitations of conventional cardiovascular medicine. The present study focus on the preparation of nanoparticles with resort to the emulsification and solvent evaporation method, using the spermine-modified acetalated dextran as polymer for selective drug delivery of a cardioprotective drug. Additionally, it dwells on the subsequent functionalization resorting to crosslinking chemistry and using propylene glycol as a bioconjugate, given its hydrophilic properties and ability to prolong the nanoparticles’ plasma half-life. The process and formulation variables, explored in this investigation, whether on preparation or functionalization, revealed to be of crucial importance to the nanosystem’s characteristics. The optimization, on propylene glycol conjugation, was not possible, for the drug-loaded nanoparticles, within the time frame set for the experimental work. Upon PEGylation, major improvements were verified in colloidal stability (assessed in cell culture medium) and cytocompatibility (assessed in rat myoblasts). The drug release did not follow the pH-sensitive solubility pattern of the polymer, that is, with burst release in acidic conditions and sustained release in neutral pH. Several points to take in consideration and suggestions, for future work, are presented on how to refine this platform for intracellular nanodelivery. |
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| Autores principais: | Marques, Gonçalo Alexandre da Conceição Duarte |
| Assunto: | Heart failure Myocardial infarction Nanoparticles Spermine-modified acetalated dextran Pegylation Mestrado Integrado - 2017 |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Heart failure post-myocardial infarction remains one of the global leading causes of mortality. The therapeutics, available today, only ameliorate the symptoms, without having any preventive effect on the, functional and structural, heart-remodeling process that ensues after such ischemic event. For this, lately, nanotechnology has emerged as a possible alternative to overcome countless limitations of conventional cardiovascular medicine. The present study focus on the preparation of nanoparticles with resort to the emulsification and solvent evaporation method, using the spermine-modified acetalated dextran as polymer for selective drug delivery of a cardioprotective drug. Additionally, it dwells on the subsequent functionalization resorting to crosslinking chemistry and using propylene glycol as a bioconjugate, given its hydrophilic properties and ability to prolong the nanoparticles’ plasma half-life. The process and formulation variables, explored in this investigation, whether on preparation or functionalization, revealed to be of crucial importance to the nanosystem’s characteristics. The optimization, on propylene glycol conjugation, was not possible, for the drug-loaded nanoparticles, within the time frame set for the experimental work. Upon PEGylation, major improvements were verified in colloidal stability (assessed in cell culture medium) and cytocompatibility (assessed in rat myoblasts). The drug release did not follow the pH-sensitive solubility pattern of the polymer, that is, with burst release in acidic conditions and sustained release in neutral pH. Several points to take in consideration and suggestions, for future work, are presented on how to refine this platform for intracellular nanodelivery. |
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