DUGi

Plantejament d’un disseny experimental amb models animals per provar l’eficàcia d’un nou fàrmac antitumoral

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@28546

This final bachelor project focuses on photodynamic therapy (PDT), an emerging therapeutic strategy in cancer treatment. PDT combines the administration of a photosensitizing agent (PS), the presence of molecular oxygen, and exposure to a light source to generate reactive oxygen species (ROS) capable of selectively destroying tumour cells. Through a comprehensive literature review, the main molecular mechanisms involved in PDT have been identified, as well as the most used families of photosensitizers and their limitations, such as phototoxicity, low solubility, and poor tumour selectivity. Regarding preclinical research, the use of animal models to assess the toxicity and efficiency of PDT agents has been explored. Studies using Galleria mellonella were reviewed, highlighting its advantages as an invertebrate model: low cost, easy handling, and no strict ethical regulation. In addition, murine models such as the BALB/c mouse strain have been considered for more advanced studies on pharmacokinetics, biodistribution, and therapeutic effectiveness. Based on this analysis, an experimental design is proposed. The first phase includes an acute toxicity study using the determination of the LD₅₀ in G. mellonella, followed by a second phase involving mice to determine the maximum tolerated dose (MTD), plasma drug kinetics, and organ distribution using sensitive techniques such as ICP-MS. Furthermore, the application of PBPK models is considered to improve the translation of preclinical data to human contexts. This work offers a solid conceptual basis and a methodological approach for evaluating the safety and effectiveness of new PDT agents in oncology, combining molecular understanding with ethical and applicable animal model

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