Stimuli sensitive hydrogels for ophthalmic drug delivery: A review

Abstract

Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist for past 10-20 years. As an isolated organ, eye is very difficult to study from a drug delivery point of view. Despite this limitation, improvements have been made with the objective of maintaining the drug in the biophase for an extended period. A major problem in ocular therapeutics is the attainment of an optimal drug concentration at the site of action. To achieve effective ophthalmic therapy, an adequate amount of active ingredient must be delivered and maintained within the eye. The most frequently used dosage forms, i.e., eye solution, eye ointments, eye gels, and eye suspensions are compromised in their effectiveness by several limitations leading to poor ocular bioavailability. Ophthalmic use of viscosity-enhancing agents, penetration enhancers, cyclodextrins, prodrug approaches, and ocular inserts, and the ready existing drug carrier systems along with their application to ophthalmic drug delivery are common to improve ocular bioavailability. Amongst these hydrogel (stimuli sensitive) systems are important, which undergo reversible volume and/or sol-gel phase transitions in response to physiological (temperature, pH and present of ions in organism fluids, enzyme substrate) or other external (electric current, light) stimuli. They help to increase in precorneal residence time of drug to a sufficient extent that an ocularly delivered drug can exhibit its maximum biological action. The concept of this innovative ophthalmic delivery approach is to decrease the systemic side effects and to create a more pronounced effect with lower doses of the drug. The present article describes the advantages and use stimuli sensitive of hydrogel systems in ophthalmic drug delivery.

In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan

“…Gellan gum (GG) [6][7][8] has been proposed to increase ocular bioavailability in the ophthalmic formulation because of its reticular properties due to eye tears divalent cations and calcium. Gellan gum is a high molecular weight and linear anionic heteropolysaccharide produced by aerobically bacteria Aeromonas (Pseudomonas) elodea, which is composed of a tetrasaccharide repeating unit of glucose, glucuronic acid and rhamnose [9,7]. Carrageenan's are another group of natural polymers which can be proposed for use in the ophthalmic formulation [10,11].…”

Hydrogels for Controlled Pulmonary Delivery

“…These external conditions can be used as triggers to more specifically control drug release in a 'smart' manner. These bioresponsiveness switches turn drug release on and off according to spatial or temporal requirements of the drug, thus reducing the frequency of drug administration and the side effects due to off-targeting and undesired body distribution [44,45].…”

Hydrogel Biomaterials for Application in Ocular Drug Delivery

“…However, the development of pH-sensitive gels must take into account the delicate environment of the eye. The formulation must have a buffer capacity that can form a gel when placed into the eye but not cause damage to the eye (Kushwaha et al, 2012).…”

“…Although many of the polymers used in pH-sensitive hydrogels are synthetic polymers, such as carbopol [polyacrylic acid (PAA)] and polyethylene glycol, natural biopolymers are also used in the formulations to give them more favorable characteristics (Kushwaha et al, 2012;Wu et al, 2013). For example, in a study performed by Kumar and Himmelstein (1995), it was shown that, although PAA is able to change from a low viscosity liquid when in an acidic solution to a gel at a higher pH, the amount of PAA needed for this to occur was too high.…”