Recent advance technique for ocular drug delivery by Gupta et al.: Nanoparticle laden in situ gel.

The article titled “Nanoparticles laden in situ gel for sustained ocular drug delivery” by Gupta et al. (J. Pharm Bioall. Sci. 5(2) 162-5) is an important contribution in the field of ocular drug delivery.[1] In order to improve bioavailability, this group combined the effects of in situ gel and nanoparticles and termed this combination as “nanoparticles-laden in situ gel,” i.e. poly(lactic-co- glycolic) acid nanoparticle incorporated in chitosan in situ gel for sparfloxacin ophthalmic delivery.

Considering the barriers created by the anatomy and physiology of eyes, it is critical to develop the drug delivery system that allows the solution to stay at the eye surface for longer time, increases its bioavailability, and maintains the stability of dissolved drug. Extensive research has been done to prolong ocular retention of drugs in the solution state by enhancing the viscosity or altering the pH of the solution by designing polymeric drug delivery systems. However, among all these, in situ gel systems have received considerable attention. But the group found that in situ gel and nanoparticles have their own limitations. It has been noticed that a reasonable strategy to circumvent the drawbacks of individual technologies is to combine technologies. Therefore, in order to address these issues and overcome the limitations, the group combined both these formulation strategies as nanoparticles suspended in liquid dosage form suitable to be administered by instillation into the eye which, upon exposure to physiological conditions, changes to the gel phase, thus increasing the precorneal residence time of the nanoparticles and enhancing ocular bioavailability.

We are aware that viscosity, hydrogen ion concentration, osmolality, and the instilled volume influence the retention of a solution in the eye. A cationic polymer chitosan was used which acted both as a pH-sensitive and permeation enhancer. Also, due to the mucoadhesive property of chitosan, in situ gel-based formulation cleared at the slowest rate as compared to nanosuspension and retained at the corneal surface for the longest time duration. Further, the viscosity of chitosan is raised due to change in physiological conditions of pH (>7). Gupta et al. found good spreading and retention of formulation in gamma scintigraphy studies, in comparison to marketed formulation. This combination will allow nanoparticles to stay for longer duration and provide optimum drug release.

Although these novel developments have been studied, researched, and designed, still these systems have not yet been commercialized. It is required to test these formulations with the available ocular drugs. It will be important to know the superiority of this approach on the available drugs in the market. I congratulate Dr. Himanshu Gupta for this excellent study.