Salecan-Clay Based Polymer Nanocomposites for Chemotherapeutic Drug Delivery Systems; Characterization and In Vitro Biocompatibility Studies.

Paula Ecaterina Florian,Paula Ecaterina Florian,Bogdan Trica,Raluca Ianchis,Elvira Alexandrescu,Anca Roseanu,Silviu Preda,Madalina Icriverzi,Claudia Mihaela Ninciuleanu

doi:10.3390/ma13235389

Abstract

Salecan is a microbial polysaccharide suitable to obtain hydrogel for biomedical applications due to the excellent hydrophilicity and biocompatibility properties. In this work, Salecan of different concentrations was introduced into polymethacrylic acid (PMAA) in the presence of clay to form novel semi synthetic hydrogel nanocomposites systems and loaded afterwards with doxorubicin (DOX). The physical–chemical characteristics of the nanocomposites systems and their effect on the viability, and morphology of MDBK (Madin–Darby bovine kidney), HT-29 human colorectal adenocarcinoma and Colo 205 human colon adenocarcinoma cell lines were investigated. DOX release from the nanocomposite systems, cell up-take and subsequent effect on cell proliferation was also analyzed. It was found that Salecan concentration determined the swelling behavior, structural parameters and morphological features of the nanocomposite systems. The hydrogen bonds strongly influenced the formation of PMAA–Salecan–clay systems, each component bringing its own contribution, thus demonstrating the achievement of an advanced crosslinked network and a more compacted hydrogel nanocomposite morphology. All the synthesized nanocomposites had negligible toxicity to normal MDBK cells and chemoresistent HT-29 cell line, whereas in the case of Colo 205 cells a decrease by 40% of the cell viability was obtained for the sample containing the highest amount of Salecan. This effect was correlated with the lowest pore size distribution leading to highest available specific surface area and entrapped amount of DOX which was further released from the nanocomposite sample. Corroborating all the data it can be suggested that the synthesized nanocomposites with Salecan and clay could be good candidates as vehicles for chemotherapeutic agents.

Highlights

To improve efficiency and specificity of anti-tumoral drug delivery while reducing therapeutic drugs side effects and toxicity, encapsulation of chemotherapeutic compounds represents an attractiveMaterials 2020, 13, 5389; doi:10.3390/ma13235389 www.mdpi.com/journal/materialsMaterials 2020, 13, 5389 approach
Free DOX exhibited a cytotoxic effect in the case of normal MDBK cells, as opposed to DOX included in hydrogel nanocomposites. These findings show that hydrogel based nanocomposite containing DOX, with the highest amount of Salecan (PCS3), is nontoxic on normal cells, but at the same time is efficient in decreasing the cancer cells proliferation
Novel nanocomposites systems based on semi synthetic networks in the presence of organomodified clay were successfully prepared and investigated

Summary

Introduction

To improve efficiency and specificity of anti-tumoral drug delivery while reducing therapeutic drugs side effects and toxicity, encapsulation of chemotherapeutic compounds represents an attractiveMaterials 2020, 13, 5389; doi:10.3390/ma13235389 www.mdpi.com/journal/materialsMaterials 2020, 13, 5389 approach. By adding clay as inorganic component, hydrogel nanocomposites acquired improved features of principally-enhanced and thermo-mechanical properties, increased swelling capacity, and water permeability. Their great specific surface and charging make clay nanoparticles able to adsorb bioactive molecules and to increase their stability [7,8,9,10]. Several studies proved that the encapsulation of clay layers into hydrogels influenced the burst release phenomena and induced a long term sustained drug delivery These findings are closely linked with the dispersion degree of the silicate sheet inside the macromolecular crosslinked system as well as to the silicate type and its hydrophobic–hydrophilic features [5,8,11]

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