Hydrogels of poly(ethylene glycol): mechanical characterization and release of a model drug
Introduction
Thermosensitive hydrogels are a class of hydrogels of great interest in the pharmaceutical and biomedical fields, as evidenced by the large amount of published literature 1, 2, 3, 4, 5, 6. They include various polymers, such as N-substituted acrylamide, methylacrylamide, poly(ethylene oxide), etc.
In addition to their fundamental scientific interest, thermosensitive hydrogels have been used in a large number of applications such as sensors, switchs, separation membranes, adsorbents, mechano-transducers, dehydrants and materials for drug delivery system [7]. Several authors 8, 9have reported that the kinetics, duration, and rate of drug release from hydrogels are influenced by the structural properties of polymer and, more particularly, the degree of crystallinity, size of crystallites, degree of swelling and molecular weight between crosslinks.
Recently, hydrogels based on poly(ethylene glycol) (PEG) have attracted considerable attention in controlled release technology because of their good biocompatibility and excellent physicochemical properties. Graham and McNeill 10, 11reported the prolonged delivery of a variety of bioactive materials, such as prostaglandin E2, caffeine and melatonin, from these hydrogels. Merril et al. [12]studied the diffusion of tricyclic antidepressants, cyanocobalamin and proteins through poly(ethylene oxide) hydrogels prepared by electron beam irradiation of aqueous solutions, and have related the diffusion coefficients to the molecular weight between crosslinks.
In this paper we describe the preparation of networks based on poly(ethylene glycol). A wide range of PEG networks of various crosslinking densities was obtained by varying the amount of crosslinking agent and the molar mass of the polymer (400≤ M ≤10 000).
These systems have been characterized by their degree of swelling as a function of temperature (T<LCST (lower critical solution temperature)), by their Young's modulus and by their molecular weight between crosslinks determined from the classical theory of gelation. The relationship between Young's modulus and polymer concentration was established, and compared with theoretical predictions proposed by de Gennes in order to discuss the structure of the networks.
The release properties of these hydrogels were studied by the determination of the diffusion coefficient for acebutolol and by correlation of these values with network characteristics. The effect of temperature on the release properties of hydrogels was also determined and analysed in terms of competition between swelling and diffusion processes.
Section snippets
Hydrogel synthesis
The hydrogels were obtained by chemical crosslinking of the poly(ethylene glycol) through urethane groups by incorporating diisocyanate and triol according to the procedure described by Graham et al. [13].
Hydrogel synthesis
The xerogels obtained were opaque and off-white, except for the xerogels based on PEG 400 and PEG 1500 (1/2) which were transparent. In the hydrated state, opaque hydrogels became transparent. To obtain reproducible hydrogels, special precautions were taken: changes in mixing efficiency, the mixing temperature and the drying conditions were the major sources of variability.
By using a polypropylene mould (Nalgène®), or a glass mould lubricated with silicon wax (Rhodorsil®), homogeneous networks
Conclusion
A thermosensitive series of hydrogels from poly(ethylene glycol) has been synthesized. A wide range of hydrogels was obtained by varying of PEG molar mass (from 400 to about 6000) and the amount of crosslinking agent.
The results of swelling characterization have shown that:
The process of crosslinking was dependent on polymer-precursor and preparation conditions.
The swelling ability was very temperature dependent and varied considerably (up to approximately 5 times their dry weight).
Analysis of
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