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 ofintereSt 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.

A Highly Selective Rho-Kinase Inhibitor (ITRI-E-212) Potentially Treats Glaucoma Upon Topical Administration With Low Incidence of Ocular Hyperemia

“…When the parent drug is lipophilic in nature, a crucial parameter to consider is the aqueous solubility of the prodrug. 44 In the present study, chemical substitution on the urea site provided an opportunity to improve bioavailability, aqueous solubility, and PK properties. Similar to other topical antiglaucoma medications, ITRI-E-212 demonstrated a rapid onset after instillation followed by a time lag before achievement of peak IOP.…”

SG-SP1 Suppresses Mast Cell-Mediated Allergic Inflammation via Inhibition of FcεRI Signaling

“…Natural products-originated compounds have been considered safe sources of new drug candidates from decades (30). These compounds could be ameliorated by chemical modifications (31). Epigallocatechin gallate (EGCG), a major component of green tea, is known to have many biologic activities including anti-oxidation, anti-inflammation, and anti-bacterial/viral infections (32)(33)(34)(35)(36)(37).…”

Chemistry, Manufacturing, and Control of Ophthalmic Formulations

“…For example, prodrugs of various prostaglandins showed substantial higher bioavailability compared to parent compound and are used in marketed products for treatment of open-angle glaucoma. Esters of pilocarpine were developed with enhanced aqueous stability [20][21][22][23][24][25].…”