Chitosan-based drug delivery systems – optimization and modelling

• Autor(a) principal: Sousa, Ana Isabel Araújo Manuel Machado de
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/45950
• topic: chitosan nanoparticles; coated superparamagnetic iron oxide nanoparticles; doxorubicin; drug release; mathematical modelling; o-HTCC nanoparticles; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

The increase of cancer incidence on the last decades and the non-existence of totally ef-ficient therapies, leads to an urgent need to develop new cures or enhance the therapies al-ready in use. Chemotherapy has been one of the most used therapies for cancer disease, and although it is very efficient in destroying malignant cells, it also comes with many disadvantages for the patients, especially due to its lack of specificity to tumour cells. In this work, all studies were made using doxorubicin (DOX), a drug commonly used in chemotherapy that apart from destroying cancer cells, also lead to future cardiotoxicity problems to the patients. A targeted drug delivery system was studied in this work, using two biopolymers, chitosan and one of its derivatives, o-HTCC, taking advantage of their pH-sensitivity. Doxorubicin was encapsulated in both chitosan and o-HTCC nanoparticles and also in superparamagnetic iron oxide nanoparticles (SPION’s) coated with both chitosan and o-HTCC. DOX release experiments were performed for different pH mediums, representing different in-vivo situations: bloodstream (7.4), tumour cells environment (6.5) and endosomal/lysosomal compartments (4.5). It was verified that an initial burst effect occurs, especially in more acidic medium, and a controlled release was then achieved. A higher drug release was observed in pH 4.5 in all nanocarriers in study. Mathematical models were applied to the data, finding that Weibull and Korsmeyer-Peppas models are the best fit in describing DOX release mechanism. It was concluded that DOX release happened through a complex and anomalous mechanism for almost all the samples, probably due to the swelling behaviour of the polymers. A study of the influence of polymer molecular weight was also performed and it was con-cluded that this parameter only has influence in nanoparticles’ size. This work indicates that these nanocarriers can be further developed for targeted drug delivery systems, especially with doxorubicin.