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

Authors Sanna V, Roggio AM, Siliani S, Piccinini M, Marceddu S, Mariani A, Sechi M

Received 7 August 2012

Accepted for publication 12 September 2012

Published 17 October 2012 Volume 2012:7 Pages 5501—5516

DOI https://doi.org/10.2147/IJN.S36684

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Vanna Sanna,1 Anna Maria Roggio,1 Silvia Siliani,1 Massimo Piccinini,1 Salvatore Marceddu,2 Alberto Mariani,3 Mario Sechi3

1
Porto Conte Ricerche, Alghero, Italy; 2Istituto di Scienze delle Produzioni Alimentari (ISPA), Consiglio Nazionale delle Ricerche (CNR), Sezione di Sassari, Italy; 3Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy


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.

Keywords: resveratrol, nanochemoprevention, PLGA, chitosan, alginate, nanoparticles

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