Hydrogel as a drug delivery system A review

Types of Hydrogels

7. TYPES OF HYDROGELS
7.1 pH Sensitive Hydrogels 3, 6 pH sensitive polymer network consist of a backbone polymer carrying weak acidic or basic groups. The backbone provide a mechanical stability of the gel where as the ionisable group contributes to the to the pH sensitivity. As mentioned such synthesis can be performed as a cross linking reaction between polymer molecules or as a cross linking polymerization, which is simultaneously synthesizing polymer chains and linking them concomitantly. i.e. poly(vinyl alcohol), poly(acrylic acid) networks have been synthesized by cross linking poly(vinyl alcohol), poly(acrylic acid). Both water solved components must be mixed, dried and finally cross linked by heating. By variation in the ratio between the backbone polymer poly(vinyl alcohol)and poly(acrylic acid) Or by the cross linking parameters both mechanical properties and sensitivity can be adjusted. The composition of hydrogel determines the pKa value and nature (acidic or basic) of the ionisable components necessary for the special sensor application. They further classified as 1) anionic 2) cationic 3) neutral. 7.2 Temperature Sensitive Hydrogels 3,6 Thermo sensitive hydrogels are one of the widely studied responsive polymer system. The thermosensitive polymers are characterized by the presence of hydrophobic groups, such as methyl, ethyl, propyl groups. The most widely studied temperature sensitive polymer is poly (N-isopropylacrylamide) p (NIPAAm) is a non biodegradable polymer with LCST 320 C in water and crosslinked gels of this material collapse around this temperature. Plurpnics or Poloxomers are commercially available co polymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO). These copolymers show phase change from sol gel around body temperature, and are used as injectable implants. They are classified into Negatively thermo sensitive Positively thermo sensitive

Department of Pharmaceutics, SDPC, Kim.

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Hydrogel as a drug delivery system A review

Types of Hydrogels

7.3 Thermally Reversible Gel 1 IPNs (inter penetrating polymer networks) of poly(acrylic acid) and polyacrylamide (PAAm) or poly(acrylamide-co-butyl methacrylate), have positive temperature dependence of swelling. Such types of hydrogels are called as positively thermo sensitive hydrogels. The negative thermo sensitive hydrogel include P(NIPAAm-co-BMA) hydrogels and (IPNs) of P(NIAAm) and poly(tetramethylenether glycol) (PTMEG). This type of hydrogel swells when the temperature is decreased, and Deswell when the temperature increased. Thermo reversible gels that are widely studied, are copolymers of poly (ethylene oxide and (PPO) . To make the hydrogels biodegradable, the PPO segment of PEO_PPO-PEO block copolymers can be replaced by a biodegradable poly (L-lacticacid) segment.

7.4 Enzyme Sensitive Enzyme sensitive hydrogels are mainly used in the targeting of drugs to colon. The colon specificity is achieved due to presence of pH sensitive monomers and azo cross linking agents in the hydrogel structure. When the hydrogel pass through the GIT, the swelling capacity of the hydrogel increases as the pH increases, due to presence of pH sensitive polymers, with the swelling being highest around pH 7.4. Upon arrival in the colon, the hydrogels have reached a degree of swelling that makes the crosslinks accessible to the enzymes (azoreductase) or mediators. Subsequently the hydrogel network is progressively defraded via cleavage of cross links, and drug entrapped is thus released. The hydrogels can be obtained by cross links polymerization of N substituted (meth) acrylamides, N tertbutylacrylamide and acrylic acid, with 4,42-di(methacryloylamino) azobenzene,4,42-di (Nmethacryloylamino 6 aminohexanoylamino) or 3,32,5,52-tetrabromo-4, 4, 42, 42-

tetrakis(methacryloylamino) azobenzene as cross linking agents.

7.5 Complexing Hydrogels Some hydrogels may exhibit environment sensitivity due to the formation of the polymer complexes. Polymer complexes are insoluble, macromolecular structure formed by the non-covalent association of polymers with the affinity for one another. The complexes formed due to association of repeating units on different chains (inter polymer complexes) or on separate region of the same chain (intra polymer complexes). Polymer complexes are classified by the nature of association as stereo complexes, poly electrolyte complexes, and hydrogen bonded complexes. The stability of the association is dependent on such factors as

Department of Pharmaceutics, SDPC, Kim.

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Hydrogel as a drug delivery system A review

Types of Hydrogels

the nature of swelling agent, temperature, type of dissolution medium, pH and ionic strength, network composition and structure and length of interacting polymer chains. In this type of gel, complex formation results in the formation of physical crosslinks in the gel. As the degree of effective cross linking is increased, the network mesh size and degree of swelling is significantly reduced. As a result, the rate of drug released in these gels decreases dramatically upon the formation of interpolymer complexes. 7.6 Light Sensitive System6 These are used in the development of photo responsive artificial muscle or as the in situ forming gels for cartilage tissue engineering. In the last study gels that may undergo trans dermal photo polymerization after subcutaneous injection were found to be applicable for drug release devices. The UV sensitive hydrogels were synthesized by introducing a leuco derivative molecule, bis(4-dimethylamino) phenylmethylleucocyanide into the polymeric network. Visible light sensitive hydrogels were synthesized by introducing a alight sensitive chromophore ( trisodium salt of copper chlorophylline) to poly(NIPAAM) hydrogels. When light is applied to hydrogel, the chromophore absorbs light which is dissipated locally as heat by radiationless transition increasing the local temperature of hydrogel and this alters the swelling behavior of poly (NIPAAM) hydrogels. 7.7 Ion Sensitive System6 Polymers may undergo phase transition in presence of various ions. Some of the polysaccherides fall in this class of ion sensitive hydrogels. While carageenan forms rigid, brittle gels in reply of small amount of k+, carageenan forms elastic gels mainly in presence of Ca+2. Gellan gum commercially available as gelrite is an anionic polysaccharide that undergoes in situ gelling in presence of mono and divalent cations, including Ca+2, Mg+2, K+, Na+. Gelation of low methoxy pectins can be caused by divalent cations, especially Ca+2. Likewise alginic acid undergoes gelation in presence of divalent/polyvalent cations e.g. Ca+2 due to the interaction with guluronic acid blocks in alginate chains.

7.8 Magnetically Responsive System Magnetically responsive systems consist of polymers or co-polymers containing magnetic micro beads. These systems can be prepared from most polymers: however, the
Department of Pharmaceutics, SDPC, Kim. 27

Hydrogel as a drug delivery system A review

Types of Hydrogels

most commonly used co-polymer for these systems is hydrophobic polymer, poly (ethlenecoinyl acetate)(PEVAc). Such systems are not typically classified as hydrogels because they do not swell to any appreciable degree. The three-dimensional structure of these system is such that no drug release can occur when no magnetic field is applied, the micro beads pulsate a line for the formation of micro pores. Additionally the pulsation of beads squeezes the drug out of the gel through these pores. When the field is removes, the drug is halted rapidly. Such systems have been target for use as pulsatil drug delivery vehicles and have shown to exhibit extremely reproducible behavior. 7.9 Electrical Sensitive 6 Electrical current can also be use an environmental signal to induce responses of hydrogels. Hydrogel sensitive to electrical are usually made of poly electrolytes. Sensors transducers are components, which convert the non electrical changes of properties of the stimuli responsive hydrogel in to a valuable signal, in most cases an electrical signal. Two basic principles used in gel sensors are: Transducers based on mechanical work performed by hydrogel swelling and shrinking Transducers observing changes in properties (eg. Density, mass, volume, stiffness) of free swelling gels. An electrical field as an external stimulus has advances, such as the availability of equipment, which allows precise control with regards to magnitude of current, duration of electrical pulses, interval between pulses, etc.

7.10 Glucose Sensitive 6 Important stimuli responsive delivery system using hydrogels that can release insulin have been investigated. Cationic pH sensitive polymers containing immobilized insulin and glucose oxidase can swell in response to blood glucose level releasing the entrapped insulin in a pulsatile fashion. Another approach is based on a competitive binding of insulin or insulin and glucose to a fixed number of binding sites in concanavalin A, where insulin is displaced in response to glucose stimuli, thus functioning as a self regulating insulin delivery system.

Department of Pharmaceutics, SDPC, Kim.

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