High molecular weight chitosan based nanogels for resveratrol delivery

ALAIMO, AGUSTINA; DOMINGUEZ RUBIO, ANA PAULA; PÉREZ, OSCAR EDGARDO; MARTÍNEZ, KARINA; ACEBEDO, SOFÍA LORENA; BUOSI FLORENCIA; DI SANTO, MARIANA CAROLINA; SPAGNUOLO, CARLA CECILIA

Ciudad Autónoma de Buenos Aires

Simposio; Exploring the Frontiers of Chemistry: Challenges for the 21st Century; 2019

Facultad de Ciencias Exactas y Naturales (UBA) y Ben-Gurion of the Negev University (Israel)

The retinal tissue has the highest oxygen uptake and glucose oxidation relative to any other tissue, which makes it more susceptible to oxidative stress. Constant light irradiation and atmospheric oxygen contribute to oxidative stress as the key factor for the ocular degenerative diseases. Whenever the antioxidant defense systems are depleted or not functional, vision impairment might be observed. For this reason antioxidants are fundamental agents in prophylactic forms of oxidative diseases. Nanotechnology becomes an option in antioxidant protection, stability, bioavailability, and therapeutic efficacy. Therefore, the aim of this work is to develop nanoparticles (NPs) as carriers of antioxidants for the ocular diseases prevention. Particularly, there is an increased interest in the therapeutic effects of Resveratrol (RSV). RSV is a naturally occurring polyphenolic compound, mainly found in black grapes and peanuts. Previous studies have demonstrated the various beneficial effects of RSV on human health, including its neuroprotection, antiinflammatory action, potent antioxidant activity and anti-aging effects. On the other hand, chitosan (CHI) is an available polysaccharide extensively studied for drug delivery systems due to the biological properties such as its relative non toxicity, biocompatibility, biodegradability and mucoadhesive characteristics. CHI and the cross-linking agent tripolyphosphate-sodium (TPP) can form biocompatible micro nano-spheres that can be efficiently employed in bioactive delivery. Hence, we designed and developed chitosan-based nanocarriers for RSV encapsulation to overcome this physicochemical and pharmacokinetic limitations. Our results included thedesign of colloidal NPs of CHI-TPP obtained by ionic gelation. The particle size distribution and the Z-potential were recorded by DLS. The peak of the majority population was located at 144 nm and the obtained value of the Z-potential was 21±4 mV, indicating that the suspension of the NPs is relatively stable. In addition, the protective effect of CHI against UV-induced photodegradation of RSV was determined. Also, TEM images showed spherical particles. Biological studies performed in human retinal pigment epithelial cells (ARPE-19 cells, ATCC) revealed that both free CHI and NPs were not cytotoxic. Also, uptake and intracellular incorporation was monitored through fluorescence microscopy. Finally, we obtained an 80% of loading efficiency of the NPs, measured using absorption spectrophotometry. In conclusion, we suggest that NPs could be a potential carrier for the bioactive, opening the possibility of its application for ophthalmic uses.