Metal alginates for polyphenol delivery systems: Studies on crosslinking ions and easy-to-use patches for release of protective flavonoids in skin

João Silva; Pavlo Vanat; Dorinda Marques-da-Silva; Joaquim Rui Rodrigues; Ricardo Lagoa

doi:10.1016/j.bioactmat.2020.03.012

Metal alginates for polyphenol delivery systems: Studies on crosslinking ions and easy-to-use patches for release of protective flavonoids in skin

Bioact Mater. 2020 Apr 6;5(3):447-457. doi: 10.1016/j.bioactmat.2020.03.012. eCollection 2020 Sep.

Authors

João Silva¹, Pavlo Vanat¹, Dorinda Marques-da-Silva¹, Joaquim Rui Rodrigues^{1

2}, Ricardo Lagoa^{1

3}

Affiliations

¹ School of Technology and Management, Polytechnic Institute of Leiria, Portugal.
² Laboratório Associado LSRE-LCM, School of Technology and Management, Polytechnic Institute of Leiria, Portugal.
³ UCIBIO-Faculty of Science and Technology, NOVA University of Lisbon, Portugal.

Abstract

Incorporation of bioactive natural compounds like polyphenols is an attractive approach for enhanced functionalities of biomaterials. In particular flavonoids have important pharmacological activities, and controlled release systems may be instrumental to realize the full potential of these phytochemicals. Alginate presents interesting attributes for dermal and other biomaterial applications, and studies were carried here to support the development of polyphenol-loaded alginate systems. Studies of capillary viscosity indicated that ionic medium is an effective strategy to modulate the polyelectrolyte effect and viscosity properties of alginates. On gelation, considerable differences were observed between alginate gels produced with Ca²⁺, Ba²⁺, Cu²⁺, Fe²⁺, Fe³⁺ and Zn²⁺ as crosslinkers, especially concerning shrinkage and morphological regularity. Stability assays with different polyphenols in the presence of alginate-gelling cations pointed to the choice of calcium, barium and zinc as safer crosslinkers. Alginate-based films loaded with epicatechin were prepared and the kinetics of release of the flavonoid investigated. The results with calcium, barium and zinc alginate matrices indicated that the release dynamics is dependent on film thicknesses, but also on the crosslinking metal used. On these grounds, an alginate-based system of convenient use was devised, so that flavonoids can be easily loaded at simple point-of-care conditions before dermal application. This epicatechin-loaded patch was tested on an ex-vivo skin model and demonstrated capacity to deliver therapeutically relevant concentrations on skin surface. Moreover, the flavonoid released was not modified and retained full antioxidant bioactivity. The alginate-based system proposed offers a multifunctional approach for flavonoid controllable delivery and protection of skin injured or under risk.

Keywords: Antioxidant dressing; Biopolymer; Epigallocatechin-gallate; Intrinsic viscosity; Topical drug delivery.