Prabhu et al. developed and investigated liposomes of brimonidine tartrate for IOP lowering effects in glaucoma. The in vitro drug release showed constant delivery of therapeutics with linear release Veliparib profile for extended time duration [68]. Also the in vivo IOP lowering effect was remarkably sustained after topical application. A potential limitation with many nanocarriers for ocular application is the

possibility of vitreous clouding after intravitreal injection. A recent study of latanoprost loaded liposome injected subconjunctivally in rabbit Inhibitors,research,lifescience,medical eyes was reported, and the IOP lowering activity was compared with conventional daily administration of latanoprost eye drop [35]. Sustained delivery for about 50 days was achieved, and the liposomes Inhibitors,research,lifescience,medical were well tolerated in vivo and no adverse effect in ocular tissue was observed with subconjunctival injection. Also, the IOP lowering

effect was superior to the conventional delivery of latanoprost by eye drops (as a standard of care option). The findings substantiated that local bioavailability and duration of action of latanoprost was improved with liposomal injection. 3. Challenges of Implantable Ocular Drug Delivery The attraction with Inhibitors,research,lifescience,medical implantable drug delivery systems in ocular diseases/disorders could be attributed to many factors which include (1) intravitreal implantation would bypass the blood-retina barrier to enhance intraocular bioavailability; (2) sustained drug release Inhibitors,research,lifescience,medical will reduce the need for daily dosing which could improve patient adherence to treatment; (3) prolonged drug release will alleviate/minimize side effects associated with repeated intravitreal injection

or systemic drug administration; and (4) effective drug delivery will avoid drug Inhibitors,research,lifescience,medical wastage while maximizing the efficacy of treatment. Despite the advantages of using implantable drug delivery system (DDS), there are a number of challenges as enumerated (Figure 1). Figure 1 Challenges of implantable drug delivery systems in glaucoma. 3.1. Polymer-Drug Interaction Understanding the factors that influence polymer degradation and drug Endonuclease release will be important in achieving sustained ocular drug release. In this regard, the type of polymer (whether homopolymer or copolymer) and the molecular weight will play substantial roles in determining hydrophilicity and the rate of degradation. For example, the hydrophilic glycolide content in PLGA is a critical parameter in determining the matrix degradation kinetics and drug release rate. PLGA 50:50 (PLA:PGA) exhibits a faster degradation rate compared to PLGA 75:25 due to higher glycolic units. Similarly, PLGA 75:25 shows faster degradation than PLGA 85:15 [69]. Hence polymers with degradation rate varying from weeks to years can be fabricated by tuning lactide to glycolide units and lactide stereoisomeric composition [56]. Another factor that affects the degradation properties is the molecular weight.