Title : Thermoresponsive in situ gelling systems for ophthalmic drug delivery
The administration of drugs through the ocular topical route supposes a considerable reduction of its bioavailability (naso-lacrimal drainage, protection mechanisms of the eye such as blinking and loss towards systemic circulation), which translates into a short therapeutic effect.
Currently, in situ gelling systems are being studied as a new alternative for the ocular topical route. They are drug controlled release systems that are in a solution phase before their administration in the eye, and which are transformed into gel after instillation. These systems are based on the use of polymers called "intelligent polymers", which its chain-structure depends on the physicochemical conditions of the environment. The principal stimuli of this mechanism are environmental parameters such as temperature, presence of ions or alteration of pH.
This presentation consists of a detailed bibliographic review of the main polymers used in these systems, focusing in thermoresponsive polymers. The mechanism of action of this type of response to temperature can be explained as follows: The temperature at which the transition from sol to gel occurs is known as gelation temperature.
When the environmental temperature (in this case, physiological temperature of the eye) is higher than the GT, the hydrogen bonds are altered and as a consequence the hydrophobic interactions increase enabling the transition between the sol and gel phases.
The most used and studied thermoresponsive polymers are: Methyl cellulose, Xyloglucan, N isopropylacrylamide and Poloxamer. Information has been gathered about the optimal concentrations of each polymer in the formula of eye drops.
Likewise, it has been observed how several authors prefer the association of different polymeric materials in order to improve their rheological properties and how this synergistic effect is translated into different commercial preparations.
The gelation involves an increase in viscosity and, therefore, an increase in resistance to naso-lacrimal drainage. This converts them into controlled release systems that prolongs the local action of drugs.
Compared with conventional delivery systems, they have the following advantages: lower frequency of dose administration and greater therapeutic adherence to the patient.