Development of novel cationic chitosan- and anionic alginate–coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol

Abstract

Background:Resveratrol, like other natural polyphenols, is an extremely photosensitive compound with low chemical stability, which limits the therapeutic application of its beneficial effects. The development of innovative formulation strategies, able to overcome physicochemical and pharmacokinetic limitations of this compound, may be achieved via suitable carriers able to associate controlled release and protection. In this context, nanotechnology is proving to be a powerful strategy. In this study, we developed novel cationic chitosan (CS)-and anionic alginate (Alg)-coated poly(d,l-lactide-co-glycolide) nanoparticles (NPs) loaded with the bioactive polyphenolic trans-(E)-resveratrol (RSV) for biomedical applications. Methods: NPs were prepared by the nanoprecipitation method and characterized in terms of morphology, size and zeta potential, encapsulation efficiency, Raman spectroscopy, swelling properties, differential scanning calorimetry, and in vitro release studies. The protective effect of the nanosystems under the light-stressed RSV and long-term stability were investigated. Results: NPs turned out to be spherical in shape, with size ranging from 135 to about 580 nm, depending on the composition and the amount of polyelectrolytes, while the encapsulation efficiencies increased from 8% of uncoated poly(d,l-lactide-co-glycolide) (PLGA) to 23% and 32% of Alg-and CS-coated PLGA NPs, respectively. All nanocarriers are characterized by a biphasic release pattern, and more effective controlled release rates are obtained for NPs formulated with higher polyelectrolyte concentrations. Stability studies revealed that encapsulation provides significant protection against light-exposure degradation, by reducing the trans-cis photoisomerization reaction. Moreover, the nanosystems are able to prevent the degradation of trans isoform and the leakage of RSV from the carrier for a period of 6 months. Conclusion: Our findings indicated that the newly developed CS-and Alg-coated PLGA NPs are suitable to be used for the delivery of bioactive RSV. The encapsulation of RSV into optimized polymeric NPs provides improved drug loading, effective controlled release, and protection against light-exposure degradation, thus opening new perspectives for the delivery of bioactive related phytochemicals to be used for (nano)chemoprevention/chemotherapy.

Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals

“…After applying the free or nanoencapsulated trans -resveratrol to the porcine skins and then exposed to UVA radiation, they found that nanoencapsulation resulted in a larger increase in the trans -resveratrol concentrations in epidermis and dermis compared to free trans -resveratrol solution [124]. Consistent with these findings, PLGA nanoparticles significantly increased the photostability of trans -resveratrol when exposed to UVA for two hours [123]. Since trans -resveratrol is more stable than cis -resveratrol and thus has been extensively used in the studies, it is the subject of this review and is referred as resveratrol in the rest of article[122].…”

“…Under UV exposure, tran -resveratrol is converted into cis -resveratrol [122]. Nanoencapsulation protects trans -resveratrol against light-exposure degradation and hence increases its stability [123,124]. Detoni CB et al compared photostability of different trans -resveratrol incorporated nanoparticles including liposomes, SLNs, nanospheres, and polymeric lipid-core nanocapsules[124].…”

Sinonasal Delivery of Resveratrol via Mucoadhesive Nanostructured Microparticles in a Nasal Polyp Mouse Model

“…Therefore, most recent studies have counteracted the low aqueous solubility of RSV by formulating it in nanoparticles, thereby increasing the specific surface area contacting the surrounding medium45464748. Nanoparticles also have the advantage of enhanced penetration through such delivery barriers as skin49 or endothelial tissues50.…”

Nanoparticle Technology for Respiratory Tract Mucosal Vaccine Delivery

“…One way to mitigate the synthetic challenges that chitosan and alginate pose is to use them as surface modifiers in pre-formed nanoparticles made from a different polymer. Using this approach, researchers were able to decorate the surface of PLGA-based nanoparticles with cationic chitosan and anionic alginate to facilitate the controlled release of resveratrol (Sanna V. et al, 2012) using a layer-by-layer nanoprecipitation method (Zhou J. et al, 2010). Images of particles produced via this approach are shown in Fig.…”