Nanohydrogels Based on Self-Assembly of Cationic Pullulan and Anionic Dextran Derivatives for Efficient Delivery of Piroxicam.

Dorota Lachowicz,Przemyslaw Mielczarek,Katarzyna Berent,Szczepan Zapotoczny,Michał Szuwarzyński,Anna Karewicz,Roma Wirecka

doi:10.3390/pharmaceutics11120622

Dorota Lachowicz, Przemyslaw Mielczarek + Show 5 more

Open Access

https://doi.org/10.3390/pharmaceutics11120622

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Journal: Pharmaceutics	Publication Date: Nov 21, 2019
Citations: 11	License type: CC BY 4.0

Affiliation: AGH University of Krakow, Jagiellonian University

Abstract

A cationic derivative of pullulan was obtained by grafting reaction and used together with dextran sulfate to form polysaccharide-based nanohydrogel cross-linked via electrostatic interactions between polyions. Due to the polycation-polyanion interactions nanohydrogel particles were formed instantly and spontaneously in water. The nanoparticles were colloidally stable and their size and surface charge could be controlled by the polycation/polyanion ratio. The morphology of the obtained particles was visualized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The resulting structures were spherical, with hydrodynamic diameters in the range of 100–150 nm. The binding constant (Ka) of a model drug, piroxicam, to the cationic pullulan (C-PUL) was determined by spectrophotometric measurements. The value of Ka was calculated according to the Benesi—Hildebrand equation to be (3.6 ± 0.2) × 103 M−1. After binding to cationic pullulan, piroxicam was effectively entrapped inside the nanohydrogel particles and released in a controlled way. The obtained system was efficiently taken up by cells and was shown to be biocompatible.

Highlights

IntroductionThere are many biologically active compounds which have a potential as highly effective drugs, but their low bioavailability (due to low solubility in aqueous media or instability in physiological conditions) or high toxicity prevent their application
There are many biologically active compounds which have a potential as highly effective drugs, but their low bioavailability or high toxicity prevent their application
The cationic pullulan, C-PUL was obtained by grafting polymer chains containing trimethylammonium groups onto the main polysaccharide chain (Figure 1)

Summary

Introduction

There are many biologically active compounds which have a potential as highly effective drugs, but their low bioavailability (due to low solubility in aqueous media or instability in physiological conditions) or high toxicity prevent their application. The polymeric matrix of the nanogels can entrap significant amount of the bioactive compound (e.g., low molecular weight drugs, proteins, DNA or RNA) and release it in a controlled way [5,6,7,8]. Sodium alginate was combined with N-isopropylacrylamide to obtain a dual-responsive system for oxytetracycline delivery, where the drug release could be effectively controlled by both pH and temperature [14]. Chitosan based nanogel which showed pH-dependent drug release which mimicked the skin cancer micro-environment was very recently proposed by Sahu et al [15]

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