Polymers with lower molecular weight will exhibit faster degradation rates because they have small polymer

chains, which degrade much faster than long polymer chains [70]. Therefore the degradation and drug release rate can be customized to achieve controlled release over several weeks to months by varying polymer ratio and molecular weight. Another important factor is the selection of therapeutic/drug molecule to match the type of implantable delivery systems. Inhibitors,research,lifescience,medical Studies using biodegradable polymers have shown that the chemical properties of drug can affect the rate of polymer degradation, rate of water absorption into the matrix, and drug release rate [71, 72]. The potential formation of polymer-drug matrix could also affect (a) stability of drugs, (b) drug release pattern, (c) safety profiles of drug and polymers, and (d) pH and osmolality of ocular fluids. Since the goal of drug delivery in glaucoma management is to improve therapeutic efficacy while minimizing systemic and local toxicity; it is very important to optimize the process of drug loading and ocular release Inhibitors,research,lifescience,medical parameters to avoid dose dumping or erratic drug release profiles. The fact still remains that only within the therapeutic window will drugs maintain balance between efficacy and safety. Even at therapeutically effective and safe drug concentrations, prolonged Inhibitors,research,lifescience,medical exposure

of ocular tissues to inserted implant might trigger inflammatory Inhibitors,research,lifescience,medical reactions to varying degrees in different patients. In recent years, prostaglandin analogs (e.g., bimatoprost, latanoprost, and travoprost) are being considered over beta-blockers (e.g., timolol maleate) as effective topical agents for lowering IOP in glaucomatous conditions. The prostaglandin analogs are enzymatically cleaved and converted to their active form after they are delivered to

the intended site [10]. Ocular implants Inhibitors,research,lifescience,medical for prodrug-based therapies should preserve the rate and extent of ocular activation to therapeutically active form of the drug. Currently a phase 1 efficacy, safety, and tolerability study of latanoprost sustained release insert is underway at the University of Kentucky [43]. 3.2. Choice of Sterilization Process All ocular implants for sustained Calpain drug release must be free from potential health hazards. As such, sterilization is required to destroy or eliminate unwanted living microorganism contamination prior to find more implantation. Sterilization can be carried out by a number of methods such as aseptic method/manufacture, gamma irradiation, heating, and gassing with ethylene oxide [73, 74]. It is known that sterilization methods could modify the polymer properties and impact drug loading and release profiles. For instance, heat sterilization could cause degradation of drug and alteration of polymer micro- and/or macroscopic mechanical properties, while autoclaving is not recommended since it can trigger drug loss or migration of drug to the outer surfaces of implants [75].