Evaluation of the Analgesic Effect of High-Cannabidiol-Content Cannabis Extracts in Different Pain Models by Using Polymeric Micelles as Vehicles.

Currently, cannabis is considered an attractive option for the treatment of various diseases, including pain management. Thus, developing new analgesics is paramount for improving the health of people suffering from chronic pain. Safer natural derivatives such as cannabidiol (CBD) have shown excellent potential for the treatment of these diseases. This study aimed to evaluate the analgesic effect of a CBD-rich cannabis extract (CE) encapsulated in polymeric micelles (CBD/PMs) using different pain models. The PEG-PCL polymers were characterized by gel permeation chromatography and 1H-NMR spectroscopy. PMs were prepared by solvent evaporation and characterized by dynamic light scattering (DLS) and transmission electron microscopy. The analgesic activity of CBD/PMs and nonencapsulated CE rich in CBD (CE/CBD) was evaluated using mouse thermal, chemical, and mechanical pain models. The acute toxicity of the encapsulated CE was determined by oral administration in mice at a dose of 20 mg/kg for 14 days. The release of CBD from the nanoparticles was assessed in vitro using a dialysis experiment. CBD/PMs with an average hydrodynamic diameter of 63.8 nm obtained from a biocompatible polyethylene glycol-block-polycaprolactone copolymer were used as nanocarriers for the extract formulations with 9.2% CBD content, which corresponded with a high encapsulation efficiency of 99.9%. The results of the pharmacological assays indicated that orally administered CBD/PMs were safe and exerted a better analgesic effect than CE/CBD. The micelle formulation had a significant analgesic effect in a chemical pain model, reaching a percentage of analgesia of 42%. CE was successfully encapsulated in a nanocarrier, providing better stability. Moreover, it proved to be more efficient as a carrier for CBD release. The analgesic activity of CBD/PMs was higher than that of free CE, implying that encapsulation is an efficient strategy for improving stability and functionality. In conclusion, CBD/PMs could be promising therapeutics for pain management in the future.

Desarrollo de vectores génicos basados en polímeros sintéticos: PEI y PDMAEMA / Development of genetic vectors based on synthetic polymers: PEI and PDMAEMA

RESUMEN En años recientes hubo un auge del uso de terapias génicas para el tratamiento de enfermedades de gran incidencia, como el cáncer. Generalmente, estas se basan en la liberación de material genético como plásmidos, en el núcleo celular, con lo cual se corrige una función o se induce la producción de proteínas deficientes a nivel fisiológico. Para llevar a cabo la terapia génica se requiere de vectores capaces de encapsular el material genético y garantizar su entrega en el núcleo celular. Los polímeros catiónicos sintéticos han llamado la atención como vectores, debido a su capacidad de condensar ácidos nucleicos para formar partículas que los protegen de la degradación enzimática y facilitan su captación celular. La polietilenimina y el polimetacrilato de N, N-dimetilaminoetilo son los polímeros catiónicos más eficaces para la administración génica. Sin embargo, estos requieren modificaciones químicas específicas para eliminar o disminuir algunas limitaciones tales como su alta citotoxicidad y baja biodegradabilidad. En este artículo se analizan algunas de estas modificaciones, enfocándose en avances recientes en el desarrollo de copolímeros anfifílicos como precursores de nanopartículas usadas como vectores génicos.

SUMMARY During recent years, the use of genetic therapies has taken relevance in the treatment of high-incidence diseases such as cancer. Usually, they are based on the release of genetic material, as plasmids, into the cell nucleus, which corrects a function or induces the production of a deficient protein at the physiological level. To carry out gene therapy, vectors capable of encapsulating the genetic material and guaranteeing its delivery in the target cell nucleus are required. Synthetic cationic polymers have attracted great attention as vectors due to their ability to condense nucleic acids to form particles that protect them from enzymatic degradation and facilitate their cellular uptake. Polyethylenimine and poly (N, N-dimethylaminoethyl methacrylate) are the most effective cationic polymers for gene delivery. However, these polymers require specific chemical modifications to either avoid or diminish their high cytotoxicity and low biodegradability. This review analyzes some of these modifications, focusing on recent advances in the development of amphiphilic copolymers as precursors of nanoparticles used as gene vectors.