Sonication-assisted Layer-by-Layer self-assembly nanoparticles for resveratrol delivery

Ana Cláudia Santos; Joana A D Sequeira; Irina Pereira; Célia Cabral; Mar Collado Gonzallez; C Fontes-Ribeiro; António J Ribeiro; Yuri M Lvov; Francisco J Veiga

doi:10.1016/j.msec.2019.110022

Sonication-assisted Layer-by-Layer self-assembly nanoparticles for resveratrol delivery

Mater Sci Eng C Mater Biol Appl. 2019 Dec:105:110022. doi: 10.1016/j.msec.2019.110022. Epub 2019 Jul 29.

Authors

Ana Cláudia Santos¹, Joana A D Sequeira², Irina Pereira³, Célia Cabral⁴, Mar Collado Gonzallez⁵, C Fontes-Ribeiro⁶, António J Ribeiro², Yuri M Lvov⁷, Francisco J Veiga³

Affiliations

¹ Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. Electronic address: acsantos@ff.uc.pt.
² Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal; i3S, Group Genetics of Cognitive Dysfunction, Institute for Molecular and Cell Biology, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
³ Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
⁴ CNC.IBILI, Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal; CEIS20, University of Coimbra, Rua Filipe Simões n° 33, 3000-186 Coimbra, Portugal.
⁵ Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal; Department of Physical Chemistry, School of Chemistry, University of Murcia, Campus de Espinardo, Via Perimetral S/N, 30100 Murcia, Spain.
⁶ Department of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga Sta. Comba, 3000-548 Coimbra, Portugal.
⁷ Institute for Micromanufacturing, Louisiana Tech University, P.O. Box 10137, Ruston 71272, LA, USA; National University of Science and Technology "MISiS", Moscow 119049, Russia.

PMID: 31546400
DOI: 10.1016/j.msec.2019.110022

Abstract

This paper advances the development of a novel drug nanodelivery solution to the oral administration of resveratrol (RSV), a low soluble drug whose recognized therapeutic applications are circumscribed when administered in the free compound form. Layer-by-Layer (LbL) self-assembly is an emergent nanotechnology proposed to address this concern with means to afford control over key formulation parameters, which are able to ultimately promote an improved pharmacokinetics. LbL self-assembly consists in the sequential adsorption of oppositely charged polyelectrolytes upon a low soluble drug nanoparticle (NP) template, giving rise to onion-like multilayered nanoarchitectures. In this work, RSV nanoprecipitation followed by LbL self-assembly of polyelectrolytes, led by a washless approach, was carried out by using the cationic poly(allylamine hydrochloride) (PAH) and the anionic dextran sulfate (DS) as polyelectrolytes towards the nanoencapsulation of RSV. Each saturated polyelectrolyte layer deposition involved the rigorous polyelectrolyte concentration assessment which was accomplished by tracing titration curves. This way, aqueous RSV nanocores and RSV LbL nanoformulations with a distinct number of PAH/DS bilayers were developed, including 2.5 (RSV-(PAH/DS)_2.5 NPs), 5.5 (RSV-(PAH/DS)_5.5 NPs) and 7.5 (RSV-(PAH/DS)_7.5 NPs) bilayered nanoformulations. Homogenous particle size distributions at the desired nanoscale interval (ca. 116-220 nm; polydispersity index below 0.15), good colloidal (zeta potential magnitudes ca. ± 20-30 mV) and chemical stabilizations, high encapsulation efficiency (above 90%) together with an excellent cytocompatibility with Caco-2 cells (cell viability above 90%) were observed for all the nanoformulations. Eventfully, LbL NPs promoted a controlled release of RSV pursuant to the number of polyelectrolyte bilayers under simulated gastrointestinal conditions, particularly in the intestine medium, emphasizing their biopharmaceutical advantage. Our findings manifestly pinpoint that LbL PAH/DS NPs constitute a promising nanodelivery system for the oral delivery of RSV, providing a rational strategy to enlarge the implementation range of this interesting polyphenol, which is possibly the most actively investigated phytochemical worldwide.

Keywords: Biocompatibility; Colloid; Controlled release; Layer-by-Layer self-assembly; Nanoparticle; Oral delivery; Resveratrol; Washless.

MeSH terms

Caco-2 Cells
Cell Death
Cell Survival
Colloids / chemistry
Drug Delivery Systems*
Drug Liberation
Humans
Nanoparticles / chemistry*
Nanoparticles / ultrastructure
Particle Size
Resveratrol / pharmacology*
Sonication / methods*
Static Electricity

Substances

Colloids
Resveratrol