Brayan Murillo Castillo

Currently, metastatic colon cancer is treated with monotherapeutic regimens such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX), capecitabine and oxaliplatin (CapeOX), and leucovorin, fluorouracil, and irinotecan hydrochloride (FOLFIRI). Other treatments include biological therapies and immunotherapy with drugs such as bevacizumab, panitumumab, cetuximab, and pembrolizumab. After the research, it was found that some mutations make those treatments not as effective in all patients. In this bibliographic review, we investigated the pharmacogenetic explanations for how mutations in the genes coding for rat sarcoma virus (RAS) and rapidly accelerated fibrosarcoma (RAF) reduce the effectiveness of these treatments and allow the continued proliferation of tumors. Furthermore, we note that patients with mutations in the dihydropyrimidine dehydrogenase (DPDY) gene usually require lower doses of therapies such as 5-fluorouracyl (5-FU) and capecitabine to avoid severe adverse effects. Some other mutations in the thymidylate synthase gene (TSYM), methylenetetrahydrofolate reductase gene (MTHFR), and ATP binding cassette transporter B (ABCB1 and ABCB2) affect efficacy and security of the treatments. It is important to address the clinical implication of the oncologist in the study of gene mutations than can influence in the antitumoral response and safety of colon cancer treatments.

Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improving patient compliance. Concerning that, this work aims to develop a suitable chitosan-based thermo-responsive scaffold to provide 24 h controlled release of Dexketoprofen trometamol (DKT). Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and FT-IR. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C, and the profiles were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 h (77.75 ± 2.72%) and reduced the burst release in the initial 6 h (40.18 ± 1.00%). The formulation exhibited a lower critical solution temperature (LCST) at 34.96 °C, and due to this phase transition, an increased release was observed at 38 °C (88.52 ± 2.07% at 12 h). The release profile for this formulation fits with Hixson–Crowell and Korsmeyer–Peppas kinetic models at both temperatures. Therefore, the developed scaffold for DKT delivery performs adequate controlled release, thereby; it can potentially overcome adherence issues and complications in wound healing applications.