Efecto de el extracto dializable de leucocitos Bovino (EDLb) en el shock endotóxico inducido por Lipopolisácaridos

[Tesis] (Doctor en Ciencias con Especialidad en Microbiología) U.A.N.L.UANLhttp://www.uanl.mx

Air Pouch Model: An Alternative Method for Cancer Drug Discovery

The tumor microenvironment (TME) is composed of cancer, immune, and stromal cells that interact through cell-to-cell contact and a diverse milieu of cytokines, chemokines, growth factors, and proteases. Several reports have linked the presence of specific cell subtypes with tumor stages, prognosis, and patient survival. Understanding cancer cell behavior and their response to treatment within the tumor microenvironment is essential to prevent establishment, growth, and progression of tumors. Many synthetic and biological agents have been tested using cell-based assays, which do not provide reliable predictive capacity for drug candidate performance in vivo. In this chapter, we discuss about the benefits of an air pouch tumor model, in which tumor cells are inoculated inside an air pouch created on the back of the mouse. The air pouch cancer model serves as a confined/localized tumor microenvironment, where direct contact of drug candidates and tumor cells is guaranteed in a tumor microenvironment context. Therefore, the efficacy of the therapeutic agent can be accurately assessed in vivo

Oral administration of pH-responsive polymeric nanoparticles based on zein and their therapeutic potential on cancer.

Background: Zein is a water-insoluble protein extracted from the endosperm of corn seeds, this polymer is an attractive matrix to encapsulate hydrophilic compounds because of its high proportion of hydrophobic amino acids, making it a potential smart delivery material for several treatments in the biopharmaceutical industry. nanoparticles have been used as drug delivery systems for the improvement of oral bioavailability; however, the strategies of nanoparticle obtention need the addition of stabilizers. in this study, a modified method to obtain zein nanoparticles was developed. Methods: Zein nanoparticles (ZNps) were made by a thermal treatment and precipitated into ovalbumin at a ratio of 1:3 on constant revolution. They were characterized by DLS, z potential, SEM, FT-IR. The encapsulation efficiency and release profile was measured following the bicinchoninic acid protocol and the viability assay was evaluated used HT29 (Human colon cancer cell line) and Huvec (Human umbilical vein endothelial cells). Results: Thermic treatment on zein allowed the obtention of ph-dependant nanoparticles without additional stabilizer, using the antisolvent precipitation method. additionally, the encapsulation efficiency was improved at 20% in comparison to other syntheses. the release profile on a gastrointestinal in vitro model of zein nanoparticles showed their capability as an oral drug delivery system; for this the egg white protein, ovabulmin, was used as a charged model. Finally, the cytotoxic effect of zein nanoparticles and zein solutions against cell lines were evaluated. zein nanoparticles highly decreased the viability on HT29 colon cancer cells in comparison to HUVEC endothelial cells. Conclusion: In this study, the synthesis of zein nanoparticles was optimized without the use of additives or stabilizers by the implementation of heat treatment. The average size of ZNps was 125 to 150 nm, these differences might be the result of the increment of protonation levels and intermolecular forces during antisolvent precipitation when a soluble protein is encapsulated. Both groups showed stability for 30 days. The wavelength splits shown on FT-IR analysis could indicate a rearrangement from tertiary to secondary structure. Encapsulation efficiency was at 70%, improving other methodologies by 20%. The release profile on a gastrointestinal in vitro model demonstrates that zein nanoparticles reach a maximum point at 240 min in acid conditions a 120 min in a basic environment, similar to an intestinal scenario providing enough time for gastric emptying. Pure zein affects the cell viability in a minor proportion compared to a nanoparticle form in both cell lines evaluated; ZNps showed a major cytotoxicity percentage in HT29 than in Huvec, which suggests a potential therapeutic effect as a drug delivery vehicle against cancer. Finally, this system has the potential to be developed as a novel strategy for an alternative to oral drug delivery and should be further studied on a wide variety of treatments