Elsevier

Life Sciences

Volume 253, 15 July 2020, 117588
Life Sciences

Formulation and comparative characterization of nanoparticles of curcumin using natural, synthetic and semi-synthetic polymers for wound healing

https://doi.org/10.1016/j.lfs.2020.117588Get rights and content

Abstract

Aim

The present research work aimed to prepare and characterize nanoparticles of curcumin using polymers from different sources like natural, synthetic and semi-synthetic, and compare their activity for wound healing. Curcumin, BCS class II drug, is a polyphenol with proven wound healing activity.

Material and methods

The curcumin-loaded chitosan and carboxymethylcellulose (CMC) nanoparticles were prepared by ionotropic gelation method. In contrast, poly-lactic co-glycolic acid (PLGA) nanoparticles were prepared by a double emulsion solvent evapouration method. The different sources of polymers include natural (chitosan), synthetic (PLGA) and semi-synthetic CMC were used for the preparation of nanoparticles.

Key findings

The percentage entrapment efficiency of curcumin-loaded nanoparticles was found to be in the order of polymers PLGA>chitosan>CMC. The in-vitro release study of carboxymethyl cellulose -curcumin nanoparticles was found to be 74.96% for 24 h. The presence of a specific peak of curcumin in all the polymeric nanoparticles specifies drug incorporation in the polymeric matrix. The in-vivo study revealed that curcumin-loaded chitosan nanoparticles fasten the healing process of the wound due to the synergistic effect produced by using a combination of curcumin and chitosan.

Significance

Curcumin-loaded nanoparticles showed significant enhancement in wound healing action by lowering the dose of curcumin and effecting synergistically due to the use of chitosan.

Introduction

A wound is an injury of tissue or organ which is caused by physical, chemical and mechanical trauma and treats with different synthetic drugs such as silver sulfadiazine, pentoxifylline, psoralen, etc. During the treatment a dose related-toxicity was mostly observed, polymeric nanoparticles act as an alternative to avoid such toxicity. The healing polymers obtained from natural, synthetic and semi-synthetic sources play a crucial role in enhancing the cell count, migration and differentiation, as they possess peculiar structure and excellent mechanical properties, and are commonly biocompatible and biodegradable. Natural polymers like polysaccharides (chitosan) have been employed in the management of wounds and burns [1]. Chitosan (CS) is used as a hemostatic agent (i.e. it rapidly clots the blood), stimulates the healing and possesses antimicrobial effects [2]. Synthetic polymers, such as polyvinyl alcohol (PVA), show wound healing property in both in-vitro and in-vivo studies. The application of poly (lactic-co-glycolic acid) (PLGA)to aid in the angiogenesis by supplying lactate and facilitates the process of wound healing [3,4]. Semi-synthetic polymers such as carboxymethyl cellulose (CMC), enhance the solubility of curcumin (CMN) as well as its bioavailability and show wound healing properties [5]. CMN is the rhizomes of Curcuma longa and uses mostly by oral, parenteral and topical routes for anti-cancer, anti-oxidant, anti-inflammatory, wound healing effect, etc. CMN (o-methoxy phenol derivative) shows antioxidant activity and aids in enzyme detoxification. When CMN is applied topically, it fastens the process of healing by inhibiting oxidative damage. The main disadvantages of CMN are its poor aqueous solubility (BCS class II drug), photosensitivity and low stability. Hence, the use of polymeric systems enhances the stability, solubility and accelerates the wound healing process [[1], [2], [3], [4], [5], [6]]. The objective of the present work was to prepare nanoparticles of CMN and study the synergistic effect with different polymers like CS, PLGA and CMC.

Section snippets

Materials and reagents

CMN was procured from Sigma Aldrich, USA. PLGA (lactide/glycolide molar ratio of 50:50) was obtained as a gift sample from Evonik, Mumbai, India. Chitosan (CS) and PVA were obtained from Fischer-Scientific, Mumbai, India. Dichloromethane (DCM) was obtained from Chemika-Biochemika-Reagents, Mumbai India. Carboxymethylcellulose sodium and ferric chloride were procured from the Research lab, Mumbai, India. All other chemicals and reagents used were of analytical grade.

Preparation of CMN-loaded CS nanoparticles

The ionotropic gelation

Particle size and zeta potential

The average particle size of formulations F1, F2, F3, F4, F5 and F6 is shown in Table 3.

Microscopy

SEM microscopy showed irregular outer characteristics of nanoparticle surface and spherical shape within a range of 10 nm to 112 nm, as shown in Fig. 1.

% Entrapment efficiency

The CS nanoparticles (F2) showed an entrapment efficiency of 91.97%. In the preparation of formulation (F2), TPP was used as a cross-linking agent with CS. Formulation F4 showed an entrapment efficiency of 92.44%, whereas formulation F6 showed 90.89% of CMN.

Discussion

The particle size of CMN-loaded nanoparticles was more significant than that of the blank nanoparticles because of the presence of the drug in the polymeric structure. Molecular weight plays a crucial role in the modulation of particle size as the smaller molecular weight of the polymer helps in achieving the smaller particle size of the formulation. Hence, CS, PLGA, CMC of low molecular weight of polymers were employed. The formulations F1 and F2 possessed positive zeta potential indicates the

Declaration of competing interest

No.

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