Retinal disorders such as age related macular degeneration and diabetic retinopathy are the leading causes of blindness. Traditional approaches in treating these diseases delay the vision loss but they will not be able to prevent vision loss. Recent understanding of the pathophysiological conditions of these diseases led to the development of drugs which not only prevent vision loss but also help in vision gain. Although drug therapy can ameliorate these disorders, delivering drugs to the retina is a formidable task. Growing evidence in the recent years indicates that the transscleral pathway can efficiently deliver therapeutic concentrations of drugs to the retina.

The aim of this research was to understand the role of various physico-chemical properties of drugs, physiological factors like choroidal pigmentation and pathophysiological conditions like diabetes on transscleral drug delivery following periocular mode of administration. Further, with the knowledge gained from above studies we have synthesized a novel prodrug to increase the retinal delivery following transscleral drug administration.

The results of the in-vitro studies have demonstrated that charge state and lipophilicity of drug are the most important parameters to be considered in transscleral drug delivery. Transscleral transport was found be highest for hydrophilic neutral drugs and least for the lipophilic positively charged drugs. In addition, the in-vitro transport studies have also revealed the rate limiting characteristics of choroid-Bruch's layer and retinal pigment epithelium (RPE) on transscleral transport. Drug accumulation and retention by sclera and melanin pigmentation in choroid-RPE were hypothesized to be the main reasons for reduction in the transport of positively charged lipophilic drugs. Periocular pharmacokinetic disposition studies of celecoxib, a lipophilic anti angiogenic drug, in albino and pigmented rats have further substantiated our earlier hypothesis on the rate limiting characteristics of drug melanin binding in transscleral drug delivery. Induction of diabetes has resulted in significant increase in the retinal delivery of celecoxib in both albino and pigmented rats. Preliminary studies in designing highly permeable prodrugs of celecoxib have shown promising improvements in retinal delivery following periocular administration.