Copolymerized PEGlyated Acrylate Hydrogels for Delivery of Dicolofenac Sodium

Hydrogels are biocompatible drug delivery systems by which the physical properties can be controlled by the cross-linking density. Hydrogels were prepared by copolymerization of acrylic acid monomers in the presence of poly(ethylene glycol)(PEG) to form polyethylene diacrylate (PEDGA). Various molecular weights of PEGs were used for the synthesis of PEGDA to study the effect of molecular weight of PEG on the properties of hydrogels. These hydrogels were further characterized for free water, swelling..
Apr 02, 2007

Hydrogels are polymeric networks that can absorb and retain large amounts of water and biological fluids and swell, still maintaining their three-dimensional structure (1, 2). These polymeric networks contain hydrophilic domains that are hydrated in an aqueous environment, thereby creating the hydrogel structure. The term network indicates the presence of cross-links, which help avoid the dissolution of the hydrophilic polymer in an aqueous medium (3–5). Hydrogels have many advantages over other drug delivery systems such as good mechanical and optical properties and biocompatibility (6, 7). The degradation products of hydrogels are usually nontoxic or have lower toxicity. Lower interfacial tension between the surface of the hydrogel and the physiological fluid helps minimize protein adsorption and cell adhesion on the hydrogel's surface. The soft rubbery nature of hydrogels also can minimize mechanical irritation when used as in vivo implants (8).

Drug release from hydrogels can be regulated by controlling water swelling and the cross-linking density of the polymers (9, 10). Because of their matrix form, hydrogels allow drug molecules to be released at a very slow rate, and when given orally, the slow release reduces gastrointestinal side effects. Hydrogels also can be given locally as transdermal drug delivery systems (11–13) and as implants (14) at or near the site of inflammation. Because of local delivery, the dose of the drugs can be further reduced.Therefore, systemic toxicity of drugs such as hepatotoxicity, blood dyscrasias, hypersensitivity, and exacerbation of asthma can be minimized. When given by injection, hydrogels help sustain drug release for a longer duration of time (15, 16).

The integrity of a drug-delivery device during its lifetime is a very important factor for its pharmaceutical use. Changing the degree of cross-linking and copolymerization facilitates achieving the desired rigidity and hardness in the hydrogels. Increasing the degree of cross-linking, however, can create a more brittle structure. Optimizing the concentration of the cross-linker, thus, is a very important factor. Copolymerization also can help achieve the desired properties of hydrogels (8). Many scientists have prepared and studied such hydrogels using copolymerization techniques (17–19). In the present work, copolymerization of poly(ethylene glycol) (PEG) and acrylic acid was carried out in the presence of polyethylene glycol diacrylate (PEGDA). Ethylene glycol diacrylate or dimethacrylate also have been used as an agent for cross-linking of preformed polymers in concentrations <1% (20–22). PEGDA of various molecular weights were used in various concentrations to study the effect the PEG's concentration and molecular weight had on the properties of the hydrogels that were formed.

Materials and methods

PEGs of various molecular weights were procured from Wilson Labs (Mumbai, India). Acrylic acid monomer and dicyclohexylcarbodiimide were procured from Himedia Laboratories (Bombay, India). The solvents and other chemicals were procured from Central Drug House, Ltd.( New Delhi, India). All the solvents and chemicals were of analytical grade. The drug, diclofenac sodium, was a gift sample from Promise Pharmaceuticals (Sagor, India).