Elsevier

Biomaterials

Volume 22, Issue 13, July 2001, Pages 1899-1909
Biomaterials

A crosslinked system from Scleroglucan derivative: preparation and characterization

https://doi.org/10.1016/S0142-9612(00)00374-4Get rights and content

Abstract

Matrices obtained by a crosslinking reaction between the polycarboxylated derivative of scleroglucan (sclerox) and 1,6-hexanedibromide have been prepared and characterized. Different ratios between the alkane dihalide and sclerox yielded products with different properties. Water uptake by the hydrogel with a low degree of crosslinking was remarkably affected by ionic strength. The determination of the crosslink density is led by simultaneously solving two Flory equilibrium equations referring to two different conditions characterized by the presence or the absence of a salt in the swelling agent. Moreover, the swelling kinetics was studied by means of a recently proposed model. Finally, the permeation of two model molecules (theophylline and polystyrene sulphonate-sodium salt) through the hydrogels was evaluated.

Introduction

Scleroglucan is a general term used to designate a class of glucans produced by fungi, especially those of the genus Sclerotium. The commercial product, termed scleroglucan, is water soluble and consists of linearly linked (1→3) β d-glucose residues with (1→6) β d-glucose residues as side chains, one for every three consecutive glucose units. This polysaccharide is dispersed as a triple helix in water, whereas it is dissolved as a single coil in methylsulfoxide [1], [2], [3]. Because of its interesting rheological properties and its resistance to hydrolysis, scleroglucan has general industrial applications. As far as the pharmaceutical field is concerned, experiments performed in vitro indicate that scleroglucan is a polysaccharide suitable for sustained release formulations. In fact, it has been proposed for the formulation of monolithic swellable matrices [4], [5], [6], [7], [8] as well as for ophtalmic preparations [9]; furthermore, oxidized scleroglucan (sclerox) was proposed for a pH-controlled delivery from oral dosage forms [10], [11].

In a previous paper [12] we have shown a part of our studies on a new type of hydrogel obtained by a crosslinking reaction between sclerox and an alkane dihalide. One of the samples has been tested as a matrix for oral dosage forms. The release profiles of a model drug from the tablets prepared with this new hydrogel evidenced a sustained release. The hydrogel was also prepared as a film that was tested as a membrane capable of regulating the diffusion of active substances. We report here further studies on such promising crosslinked hydrogel concerning its characterization, in terms of water uptake and permeation experiments. A theoretical analysis of permeation experiments allows to calculate the diffusion coefficient of theophylline, used as a model drug. The swelling equilibrium data of hydrogels, collected at two different ionic strengths, are analyzed applying a strategy, based on the Flory–Rehner theory, to estimate the crosslink density ρx of the polymer.

The swelling kinetics curves are studied applying a recently proposed theoretical approach from which it is also possible to estimate the diffusion coefficient of the solvent molecule inside the polymeric systems. An estimation of the mesh size of the hydrogel at the highest degree of crosslinking, in terms of molecular weight cut-off, is obtained by means of permeation experiments carried out with polystyrene sulphonate-sodium salt at different molecular weights.

Section snippets

Materials

Scleroglucan (Actigum CS 11) was provided by Mero-Rousselot-Satia (France). Theophylline (TPH) and NaCl were Carlo Erba products (Italy); the polystyrene sulphonate-sodium salt (PSS) of narrow molecular weight distribution (calibration kit, Mw/Mn=1.10) was purchased from Polymer Laboratories (UK). Methylsulfoxide GR dried (DMSO), used as a medium for the crosslinking reaction, was purchased from Merck (Germany). All other products and reagents were of analytical grade; distilled water was

Swelling

In Fig. 2 the relative increase of weight [(WW0)/W0] as a function of time is reported at two different temperatures (7 and 37°C) and at two r values (0.5 and 1.0). It is possible to observe that for both crosslinked polymers the increase of weight in water was not appreciably influenced by temperature variations while, as expected, it was noticeably affected by the degree of crosslinking.

The effect of environmental ionic strength on solvent uptake is reported in Fig. 3. As it is possible to

Conclusion

Reported results on the behavior of the crosslinked sclerox indicate that these new derivatives show a very high degree of swelling in water that, in the case of r=0.5, can be reduced if salt is added to the surrounding medium. The study of the swelling equilibrium in different ionic strength gives an estimation for the crosslinking density at different r values. An uncommon strategy approach to analyze the swelling kinetics has been applied obtaining a very good agreement with the experimental

Acknowledgements

This work was carried out with the financial support of C.N.R. and MURST.

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