A Synergistic Approach Therapy for Colorectal Cancer Based on Exosomes and Exploitation of Metabolic Pathways.

In order to reduce the side effects of traditional chemotherapy in the treatment of colorectal cancer (CRC), a new drug delivery system has been developed in this work, based on exosomes that can host two drugs that act synergistically: farnesol (that stops the cell cycle) and paclitaxel (prevents microtubule system depolymerization). Firstly, exosomes were isolated from different cell cultures (from colorectal cancer and from fibroblast as example of normal cell line) by different methods and characterized by western blot, TEM and DLS, and results showed that they express classical protein markers such as CD9 and HSP-70 and they showed spherical morphology with sizes from 93 nm to 129 nm depending on the source. These exosomes were loaded with both drugs and its effect was studied in vitro. The efficacy was studied by comparing the viability of cell cultures with a colorectal cancer cell line (HCT-116) and a normal cell line (fibroblast HS-5). Results showed that exosomes present a specific effect with more reduction in cell viability in tumour cultures than healthy ones. In summary, exosomes are presented in this work as a promising strategy for colorectal cancer treatment.

An Approach to Minimize Tumour Proliferation by Reducing the Formation of Components for Cell Membrane.

Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated ß-cyclodextrin Sodium Salt (SBE-ß-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 µM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer.

Tuning Alginate Microparticle Size via Atomization of Non-Newtonian Fluids.

A new approach based on the atomization of non-Newtonian fluids has been proposed to produce microparticles for a potential inhalation route. In particular, different solutions of alginate were atomized on baths of different crosslinkers, piperazine and barium chloride, obtaining microparticles around 5 and 40 microns, respectively. These results were explained as a consequence of the different viscoelastic properties, since oscillatory analysis indicated that the formed hydrogel beads with barium chloride had a higher storage modulus (1000 Pa) than the piperazine ones (20 Pa). Pressure ratio (polymer solution-air) was identified as a key factor, and it should be from 0.85 to 1.00 to ensure a successful atomization, obtaining the smallest particle size at intermediate pressures. Finally, a numerical study based on dimensionless numbers was performed to predict particle size depending on the conditions. These results highlight that it is possible to control the microparticles size by modifying either the viscoelasticity of the hydrogel or the experimental conditions of atomization. Some experimental conditions (using piperazine) reduce the particle size up to 5 microns and therefore allow their use by aerosol inhalation.