Polyphenols-Loaded Sericin Self-Assembling Nanoparticles: A Slow-Release for Regeneration by Tissue-Resident Mesenchymal Stem/Stromal Cells.

Giulia Orlandi,Milena Sorrenti,Marzio Sorlini,Silvio Faragò,Lorena Segale,Elia Bari,Carla Renata Arciola,Sara Perteghella,Maria Luisa Torre,Laura Catenacci

doi:10.3390/pharmaceutics12040381

Abstract

Mesenchymal stem/stromal cells (MSCs) are a therapeutic target to promote tissue regeneration, mainly when oxidative stress-mediated damage is involved in disease pathogenesis. Here, slow-release silk sericin nanoparticles (SNPs) loaded with natural antioxidant polyphenols were developed to sustain regeneration by tissue-resident MSCs. SNPs were prepared by exploiting a self-assembly method with poloxamer and were loaded with proanthocyanidins (P), quercetin (Q) or epigallocatechin gallate (E). SNPs, with a diameter less than 150 nm, were able to encapsulate both hydrophilic (P and E) and hydrophobic (Q) drugs. A slow and controlled release was obtained from SNPs for all the actives in PBS, while in EtOH, Q and E showed a burst release but P did not. Kinetic models revealed lower diffusion of P than other biomolecules, probably due to the higher steric hindrance of P. The in vitro anti-oxidant, anti-elastase and anti-tyrosinase properties of SNPs were assessed: loading the P and E into SNPs preserved the in vitro biological activities whereas for Q, the anti-elastase activity was strongly improved. Moreover, all formulations promoted MSC metabolic activity over 72 h. Finally, SNPs exhibited a strong ability to protect MSCs from oxidative stress, which supports their potential use for regenerative purposes mediated by tissue-resident MSCs.

Highlights

The potential use of mesenchymal stem/stromal cells (MSCs) in tissue regeneration is based on their ability to produce a large variety of bioactive trophic factors that stimulate neighboring parenchymal cells to repair damaged tissues [1,2,3]
sericin nanoparticles (SNPs) were prepared by exploiting a self-assembly method with poloxamer; three different active ingredients were loaded into SNPs: P, Q and E
Considering the proposed structure of SNPs (Figure 1A), hydrophobic drugs should reside in the inner core of the micellar structure, while a hydrophilic drug is expected to reside within the corona, which is relatively hydrophilic

Summary

Introduction

The potential use of mesenchymal stem/stromal cells (MSCs) in tissue regeneration is based on their ability to produce a large variety of bioactive trophic factors that stimulate neighboring parenchymal cells to repair damaged tissues [1,2,3]. MSCs are considered as a therapeutic target to promote healing in many chronic and acute degenerative diseases, when oxidative stress damage is involved in the pathogenic mechanisms. Flavonoids, which have strong antioxidant activity, could effectively protect MSCs from oxidative damage and, from senescence and ageing. P are condensed tannins, which are abundantly present in flowers, fruits and seeds of various plants, where they act as a defense mechanism against pathogens and predators. Multiple biological effects have been attributed to P, Q and E, including antioxidant, anti-tyrosinase, anti-elastase, anti-inflammatory, antimicrobial and anti-cancer properties [6,7,8]. The anti-elastase activity of flavonoids may be helpful in slowing down the degradation of the elastin in tissue, which is generally caused by the excess of protease activity that follows tissue damage [9]

Methods

Results

Conclusion