Preparação e caracterização de lipossomas contendo um derivado de N-ciclohexil-1,2,4-oxadiazol como potencial agente antitumoral em linhagens de câncer colorretal (HCT-116)

Abstract

Cancer has become a major public health problem worldwide, responsible for one in six deaths worldwide. Modified drug delivery systems are pharmaceutical preparations with strong avantgarde appeal in the frontier area of knowledge. Oxadiazole derivatives are used in medicinal chemistry since they exhibit high and specific biological activities but with high toxicity. Thus, the objective of the present work was to develop and characterize a liposomal system containing a synthetic molecule of N-cyclohexyl-1,2,4-oxadiazole for evaluation of antitumor activity in vitro in tumor cell lines. The prospective study sought to build scientific, technological, and commercial panorama about liposomes and oxadiazoles. In the preparation of the liposomes, synthetic phospholipids dissolved in a chloroform/methanol solution were used. The physicochemical characterizations took place through the analysis of morphology, determination of the size and concentration of particles. In silico tests, to determine ADME / Tox properties, search for targets and structural similarity analysis were used for pharmacobiological predictions. The MTT assay tested the biological activity of the nanosystem compared to drug-free. It was found that there is no clear correlation between published articles and patents filed and, the market for liposomal and oxadiazole drugs is still incipient with few approved drugs. The results obtained in scanning and transmission microscopy corroborated each other to attest to the size of the liposome and allowed it to verify its spherical shape. The screening analysis of the nanoparticles allowed a reliable measurement of the population of encapsulated liposomes with a size of 251.4±7.8 nm, as well as their concentration of 8.62.108±4.18,107 particles/ml. The indirect calculation of encapsulation efficiency indicates that a percentage of 33% of the drug was encapsulated in the liposomes. After the proliferation inhibition test, 25% of the proliferation inhibition of PC-3 (prostate adenocarcinoma) cells HCT-116 (colorectal cancer) was observed when encapsulating twice the IC50 (50 µM), due only the action of the drug. The results of in silico prediction were promising when compared to the control drug, doxorubicin. Cellular targets allow speculation about the targets to be studied in the mechanism of action of the drug. Structural analysis, on the other hand, allowed us to identify that there are no other similar drugs documented in this study. The results observed with the encapsulated drug have shown promise compared to previous studies with the free drug, however further studies on the action of the drug on the cell cycle and its encapsulation efficiency need to be developed.