Elsevier

Carbohydrate Polymers

Volume 76, Issue 3, 9 April 2009, Pages 464-471
Carbohydrate Polymers

Polyelectrolyte complexes of gum kondagogu and chitosan, as diclofenac carriers

https://doi.org/10.1016/j.carbpol.2008.11.010Get rights and content

Abstract

Polyelectrolyte complexes (PEC) of gum kondagogu (GKG) and chitosan were prepared by mixing polymeric solutions of different concentrations (0.02–0.18% w/v). The complex formed were loaded with diclofenac sodium, and the release of the drug was measured in vitro and in vivo, along with the measurement of particle size, zeta potential, complex formation, flow properties, and loading efficiency. Maximum yield of PEC was observed at gum kondagogu concentrations above 80%. The PEC showed lower release of diclofenac sodium in 0.1 N HCl as compared to phosphate buffer (pH 6.8). Increasing the concentration of gum kondagogu in PEC led to an increase in drug release. However, PEC 1:3 (gum kondagogu: chitosan) with higher concentration of chitosan showed 98% release with in 4.5 h, owing to the fact that chitosan has a higher degree of swelling in acidic medium. PEC 5:1 and 3:1 showed a 5.3- and 5.8-fold increase in relative bioavailability compared to the free drug when administered orally to the rats.

Introduction

Gum kondagogu (GKG) is a naturally occurring polysaccharide derived as an exudate from the tree (Cochlospermum gossypium). Basically it is a polymer of rhamnose, galacturonic acid, glucuronic acid, β-d-galactopyranose, α-d-glucose, β-d-glucose, galactose, arabinose, mannose and fructose with sugar linkage of (1→2) β-d-Gal p, (1→6), β-d-Gal p, (1→4) β-d-Glc p, 4-0-Me-α-d-Glc p, (1→2) α-l-Rha, with average molecular weight of 7.23 × 106–8.25 × 105 g/mol determined by static light scattering method and Berry plots (Janaki and Sashidhar, 1998, Vinod et al., 2008). GKG is composed of higher uronic acid content, protein, tannin, and soluble fibers. GKG was found to be safe in a 90-day sub-chronic toxicity study conducted in rats (Janaki & Sashidhar, 2000). Chitosan is a natural, non-toxic, biodegradable, and biocompatible polysaccharide has been used in the biomedical areas in the form of sutures, wound healing material, and for sustained release of drugs (Kumar et al., 2004, Sivakumar et al., 2002). Chitosan is a very promising biomaterial for drug delivery system; however, the use of chitosan polymer in oral administration is restricted by its fast dissolution in the stomach and its limited capacity for controlled drug delivery system (Risbud et al., 2000, Sivakumar et al., 2002). To overcome these disadvantages, many researchers have investigated the polyelectrolyte complex of chitosan with other polymers like chondroitin (ChS), carrageenan, xanthan gum (XA), sodium alginate (SA), poly vinyl alcohol (PVA), and pectin etc.; for prolonged drug delivery systems (Bhise et al., 2007, Chen et al., 2005, Dumitriu and Chornet, 1996, Kim et al., 1999, Wang et al., 1997, Yao et al., 1997). Advantage of polyelectrolyte complex of chitosan with other polymers includes the avoidance of organic solvents, chemical cross-linking agents and thereby reducing the toxicity and undesirable side effects.

Diclofenac sodium (C14H10Cl2NO2Na) is a widely used non-steroidal anti-inflammatory drug that exhibits anti-rheumatic, analgesic, osteoarthritis, and anti-pyretic activities. It has a short half-life in plasma (1–2 h). The most common adverse effects of the drug are gastritis and peptic ulceration. (Khazaeinia and Jamali, 2004, Manjunatha et al., 2007). As diclofenac sodium has short biological half-life and gastric side effects, it was chosen as a model drug for controlled delivery.

The study was aimed to develop and characterize a novel polyelectrolyte complex (PEC) from gum kondagogu and chitosan as drug carrier for controlled drug delivery. Various gum kondagogu/chitosan complexes were prepared by coacervation method using different ratios of gum kondagogu and chitosan. Diclofenac sodium was used as model drug. The polyelectrolyte complexes were evaluated for the complex formation, charge, particle size, flow properties, loading efficiency, and drug release in vitro and in vivo.

Section snippets

Materials

Carrageenan, was purchased from Sigma–Aldrich Chemical Co. Ltd. Gum kondagogu (grade-1, hand picked, fresh, clean with no extraneous material) was collected from Girijan Co-operative Corporation, a government of Andhra Pradesh undertaking, Hyderabad, India. All the buffer salts and organic solvents used in the study were from Merck, India. Pccaps kit (Capsugels Laboratories, Thailand), Diclofenac sodium was purchased from Meditech Chemicals (P). Ltd., Guargaon, Mumbai, India. High molecular

Determination of polyelectrolyte complex formation between gum kondagogu and chitosan

A clear separation of dense phase due to formation of PEC was observed in our experiment during addition of different concentration of chitosan solution to aqueous gum kondagogu solutions. Polyelectrolytes carry net −ve charge or +ve charge and exhibit specific pH, zeta potential, due to the presence of surface charge. Hence there is a possibility of neutralization of charge when polyelectrolytes of opposite charge are mixed during the formation of PEC. The zeta potential, pH and coacervate

Conclusion

This experimental investigation showed the formation of a novel polyelectrolyte complex between gum kondagogu and chitosan with diclofenac sodium as model drug. The complex formation between gum kondagogu and chitosan is via electrostatic interaction between carboxyl group of gum kondagogu and amine group of chitosan. The stoichiometric ratio for effective complex formation was found to be 4:1–5:1 (% w/w of gum kondagogu/chitosan). The diclofenac loaded polyelectrolyte complex of gum

Acknowledgements

The authors thank the Director, IICT for extending his support for the work and CSIR, New Delhi for providing Senior Research Fellowship to Mr. Naidu V.G.M. Authors also thank Dr. B. Sreedhar IICT for extending their help in carrying out TGA studies.

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