The development of new drug delivery technologies and using them in the product development is critical to the survival of pharmaceutical industry. The hydrogels are crosslinked hydrophilic homopolymers or copolymeric structures that can imbibe large amounts of water or biological fluids. The hydrogels are also called aqua gel and are having absorbent properties as they are natural or synthetic polymers containing 99 per cent of water without undergoing dissolution.
The hydrogels are rendered insoluble because of chemical or physical cross-links. The physical cross- links include crystallites entanglements or weak associations like hydrogen bonds or Vander waal forces. The cross-linking provides the physical integrity and network structure to the gel and are due to physical or chemical cross linkage of the hydrophilic polymer chains.
The hydrogel can be classified on the basis of preparation into homopolymer hydrogels, co-polymer hydrogels and multi polymer hydrogels. The classifications of hydrogel on the basis of ionic charges are neutral hydrogels, anionic hydrogels and ampholytic hydrogels. The classifications of hydrogels based on structure are as amorphous hydrogels, semi-crystalline hydrogels and hydrogen bonded hydrogels.
The advantages of hydrogels are that they may provide desirable protection of liable drugs and proteins from the potentially harsh environment in the vicinity of the release site. Hydrogel devices have been developed for delivery by almost all of the conventional routes. The important characteristics in evaluating the ability of a polymeric gel to function in a particular controlled release application are the network permeability and the swelling behaviour which dependent's on the external environment.
The hydrogels for controlled release systems are classified on the basis of drug release into swelling controlled, chemically controlled, diffusion controlled and environmentally controlled system. The hydrogels can be further classified on the basis of mechanism of controlling the release of drug into diffusion controlled release system, swelling controlled release system (Fig-1), chemically controlled release systems and environment responsive systems.
In environmentally-controlled system the swelling properties in response to external environment like change in external temperature, pH, ionic strength, enzymatic, electromagnetic radiation and chemical reaction. The organogel differs from hydrogel in the solvent used, in organogel the solvent used may be organic, mineral oil or vegetable oil and in hydrogel it is water. The materials used in the preparation of hydrogels include polymers like cellulose derivatives, natural gums, polyacrylates and gelatin.
The general methods of preparation of hydrogls is by free radical polymerization of hydrophilic vinyl polymers and cross linking by radiation like electron beams, gamma rays, X rays or U.V. light etc. The hydrogel preparation from monomer can be initiated by copolymerisation of hydrophilic monomers and polyfunctional co monomers acting as crosslinkers, which form a network like structure. The monomers are hydrophilic in nature like methacrylates and methacrylamides. The preparation of hydrogels from prepolymers can be synthesised by using hydroxyl polyethylene glycol with a diisocynate in presence of a triol as crosslinker and leads to the formation of crosslinked hydrophilic polyurethanes.
The hydrogels are one of the upcoming classes of polymer-based system with numerous biomedical and pharmaceutical applications. The natural hydrogels existing in the body include mucus, vitreous humor of eye, cartilage, tendons and blood clots. The viscoelastic nature of the soft tissue component of the body is due to this hydrogel when compared with mineral based hard tissue of skeletal system. Research is on for developing synthetically derived tissue replacement technologies derived from hydrogel for temporary implants (degradable) and permanent implants (non-degradable).
The hydrogels can be formulated in a variety of physical forms, including slabs, microparticles, nanoparticles, coatings,and films. Significant progress has been made in improving the properties of hydrogels used for drug delivery and expanding the range of drugs and kinetics that can be achieved using a hydrogel-based delivery vehicle. Several changes need to be improved for the clinical applicability of hydrogels in drug delivery. The hydrogel nanoparticulate systems based on natural ( chitosan, alginate) and synthetic (poly(vinyl alcohol), poly(ethyleneimine), ply(ethylene oxide), poly (vinyl pyrrolidone) having different properties can be used in drug delivery.
The hydrogel can be used for the gene delivery and the delivery of plasmid-beta 1 gene for wound healing, pRL-CMV for the treatment of human breast cancers and C2C12 myoblasts to protect the cell from host immune response were studied and have shown promising result. The advances in the developments of supramolecular hydrogels based on the polypseudorotaxanes and polyrotaxanes formed by inclusion complexes of cyclodextrins threading onto polymer chains.
The physical supramolecular hydrogels were prepared by self assembly of densely packed cyclodextrin rings threaded on polymer or copolymer chains acting as physical crosslinking points. The thermo-reversible and thixotropic properties of these physical supramolecular hydrogels have inspired their applications as injectable drug delivery systems. The chemical supramolecular hydrogels were synthesized from polypseudorotaxanes polyrotaxanes by chemical crosslinking of cyclodextrin or polymer chains.
Anionic hydrogels are used in the design of intelligent controlled release devices for site-specific drug delivery of therapeutic proteins to the large intestine, where the biological activity of the proteins are prolonged, and cationic hydrogels are studied for the development of self-regulated insulin delivery system, which releases the insulin in response to changing glucose concentration.
The injection of hyaluronic acid-tyramine conjugate forms biodegradable hydrogels in vivo by enzyme induced oxidative coupling and offers potential in drug delivery system and tissue engineering. The interaction of carbonyl group of Poly(vinyl pyrolidone) and carboxyl group of Poly (acrylic acid) having different gelation for drug delivery system were studied and can be used in drug delivery system, trasdermal patches and molecular imaging probes.
The dextran hydrogel containing hydroxyl group are amenable to modification and was studied for the treatment of solid tumour using doxorubicin. The crosslinking of succinic derivatives of inulin with alpha, beta-polyaspartylhydrazide to obtain INUPAHy hydrogels are useful in oral treatment of inflammatory bowel disease using glutathione and oxytocin as model drug. Inulin reacted with glycidyl methacrylate for the preparation of inulin hydrogel is successful in colonic drug targeting. The chitosan hydrogel can be used in local drug delivery carrier for agents like FGF-2 and paclitaxe for the control of angiogenesis.
The ferrogels prepared from poly(N-isopropyl acrylamide) with nano size iron oxide ferrofluids using N,N1-methylene bis- acrylamide as crosslinking agent was studied and showed positive result in drug delivery system. The chitosan hydrogel can be used as injectable scaffold in tissue engineering and orthopaedics. The new type of hydrogel HYPANTM(under trademark) has opened the avenues for targeted and controlled release system.
The hydrogels made from 2-Hydroxyethyl methacrylate could sustained the drug action for two weeks and also used in medical & dental implants. The ChonDux, a polymer hydrogel when injected into knee during surgery could regenerate the cartilage by stimulating repair cells in body. The photo polymerized hydrogel are used for various drug delivery of bioactive materials including proteins and oligonucletides. The significant water content of hydrogels offers flexibility similar to natural tissue and have potential in biomedical application.
The common ingredients used in hydrogel include polyvinyl alcohol, sodium polyacrylate, acrylate polymers and copolymers with an abundance of hydrophilic groups. The natural hydrogels are under investigation for the use in tissue engineering and the materials used include agarose, methylcellulose, hyaluronan and other naturally derived polymers. The hydrogel can be used for preparing artificial cornea, which is made of a dual network hydrogel with a clear centre and peripheral pores. The integration of the artificial cornea into the surrounding natural tissue was initiated by the cells infiltrating the pores and secreting the collagen.
The preparation of in situ- forming hydrogels, composed of oxidized dextran (Odex) and amine-containing polymers, have extensively studied for their potential use as a wound dressing to promote blood clotting. Thromboelastography was used to examine the effects of the in situ gelation on blood coagulation in vitro, where the Odex-PAA combination was found to be more pro-haemostatic, as indicated by a decrease in clotting time and could be useful in promoting clot invitro. A new synthetic gel was developed, which is made of water and fibrous polymer acrylamide will kick into gear the blood-clotting protein factor VII and stop the blood flow from deep wounds in minutes.
Hydrogels are nonadherent dressing that through semi permeable film allow a high rate of evaporation without compromising wound hydration and thus make it useful in burn treatment. The photocrosslinkabel chitosan are useful as a tissue adhesive and act as a urgent haemostat material. The hydrogel developed by the esterification of polyvinyl alcohol (PVA) with gelatine can be used for wound dressing.
The author is Assistant Prof., National College of Pharmacy, Manassery, Kozhikode, Kerala.