Prodrug strategies in ocular drug delivery

Abstract

Poor bioavailability of topically instilled drug is the major concern in the field of ocular drug delivery. Efflux transporters, static and dynamic ocular barriers often possess rate limiting factors for ocular drug therapy. Different formulation strategies like suspension, ointment, gels, nanoparticles, implants, dendrimers and liposomes have been employed in order to improve drug permeation and retention by evading rate limiting factors at the site of absorption. Chemical modification such as prodrug targeting various nutrient transporters (amino acids, peptide and vitamin) has evolved a great deal of interest to improve ocular drug delivery. In this review, we have discussed various prodrug strategies which have been widely applied for enhancing therapeutic efficacy of ophthalmic drugs. The purpose of this review is to provide an update on the utilization of prodrug concept in ocular drug delivery. In addition, this review will highlight ongoing academic and industrial research and development in terms of ocular prodrug design and delivery.

Fig. (1)

Ester prodrugs from COOH/OH functionalities.

Fig. (2)

Monoester prodrugs of Ganciclovir.

Fig. (3)

Chemical structure of prostaglandin prodrugs.

Fig. (4)

Chemical Structure of three cannabinoid (arachidonylethanolamide, R-methanandamide and noladin ether) phosphate esters.

Fig. (5)

Hydrolysis of N-(acyloxy)alkyl carbamate derivatives of timolol to parent timolol.

Fig. (6)

Hydrolysis of oxime derivatives (ethacrynic acid a an example) .

Fig. (7)

Chemical structure of phenylephrine and its oxazolidine derivative.

Fig. (8)

Chemical Structure of lipid prodrugs of 5-Fluorouracil.