Hydroxyapatite-based materials for smart antitumor drug delivery systems, endocytic pathways and endosomal trafficking
- Autores: Manuel Rivas Cañas
- Directores de la Tesis: Jordi Puiggalí Bellalta (dir. tes.), Luís Javier del Valle Mendoza (codir. tes.)
- Lectura: En la Universitat Politècnica de Catalunya (UPC) ( España ) en 2019
- Idioma: español
- Tribunal Calificador de la Tesis: Manuel Reina del Pozo (presid.), Montserrat Español Pons (secret.), Pepita Giménez Bonafé (voc.)
- Programa de doctorado: Programa de Doctorado en Polímeros y Biopolímeros por la Universidad Politécnica de Catalunya
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- Resumen
Development of new drug molecule is expensive and time consuming. Improving safety efficacy ratio of “old” drugs has been attempted using different methods such as individualizing drug therapy, dose titration, and therapeutic drug monitoring. Delivering drug at controlled rate, slow delivery, targeted delivery are other very attractive methods and have been pursued vigorously. Now a new class of bioceramics based on calcium phosphate (CaP) salts is on the verge of being widely applied in the clinic. Among various types of CaP, hydroxyapatite (HAp) have attracted more attention in biomedical fields due to its exceptional features such as biocompatibility, bioactivity, osteoconductivity and osteoinductivity.
Its "chemical similarity" with the mineralized phase of biologic bone makes it unique. HAp as an excellent carrier of osteoinductive growth factors and osteogenic cell populations. HAp can incorporate the drug molecules either physically or chemically so that the drug retains intact until it reaches to the target site. It could also gradually degrade and then deliver the drug in a controlled manner over time. So therefore, this bioceramic is an excellent candidate for targeted drug delivery regardless of its density. Careful selection of reaction conditions, reagent concentrations and adsorption agents often provides a degree of size and shape control in nanoparticles dissolution, and a considerable amount of recent research has been devoted to developing such methods.
Delivery of drug carriers to the target cells can be only a part of the whole story of successful drug targeting. Some drug carriers may have to gain access to and get inside the cytoplasm of a target cell in order to release the drug at the optimum rate for the pharmacological effectiveness. In that sense, intracellular targeting is an important systemic targeting. On the other hand, in some pathologies, especially in cancer, cell defends itself actively by using molecular ‘pumps’ in cell membrane that actively expel drugs form the interior -multidrug resistance (MDR)- and therefore their impairment is likely to have a significant therapeutic benefit. Thus, understanding mechanism of intracellular localization is critical in developing some drug delivery systems. This release is strongly influenced by resistances to mass transfer, intracrystalline diffusion and adsorpted species. The main goal of this Thesis is to design an effective MDR reversing nanoparticulate drug delivery system consists of a HAp polymeric matrix from which the drug is released intracellularly.
