Executive Summary : | In recent years, biodegradable amphiphilic block-copolymers possess the capability to form self-assembled structures in solutions. In order to use these polymers for drug delivery applications, it is crucial for them to respond to the changes closer to the body temperature. The self-assembly of these block-copolymers into hydrogels enables them to be used as polymeric scaffolds in biomaterial applications, drug delivery agents, and for tissue engineering applications. These biodegradable block copolymers that lead to the formation of micellar gel structure are highly thermoresponsive. These thermoresponsive polymers form a sol at room temperature and form a gelation structure when administered inside the body. These polymeric systems may prove to be very crucial for ocular drug delivery systems. Ocular eye drops may prove to be inefficient drug delivery agents due to rapid loss on account of tear drainage. On a similar note, prolonged usage of Ocular injections for treating adverse eye conditions such as retinal detachment, glaucoma, etc. may increase the risk of ocular hypertension and intraocular hemorrhage. Carboxymethyl cellulose (CMC) is a naturally occurring biopolymer/polysaccharide, and a hydrophobic derivative of cellulose which is used for the treatment of dry eyes, a substitute for vitreous substances, and ophthalmic surgical devices. The major scientific objective of the proposed project is to conduct a temperature-responsive study of the conformational structure of biodegradable triblock copolymer constituting polyethylene glycol (PEG) and poly(ε-caprolactone) (PCL) in the form PCL-co-PEG-co-PCL. This will serve as a promising biodegradable and thermoresponsive in-situ hydrogel which has been recently explored as a suitable drug delivery agent in aqueous solutions using atomistic simulations. The major aim is to get physical insights into the lower critical solution temperature (LCST) behavior of these thermoresponsive block copolymers constituting CMC targeting ocular drug delivery. The scientific objectives will be met by carrying out all-atom molecular dynamics simulation studies of the amphiphilic thermoresponsive block copolymers studying the effect of gelation temperature on the controlled release of CMC for in-vitro ocular drug release studies. The synergistic effect of different variables such as block length of the hydrophilic moiety in the block copolymer, temperature, polymer concentration, and added salts on the conformational structure of these block-copolymers affecting gelation and LCST will be studied. The detailed microscopic study of the amphiphilic block copolymers in an aqueous environment will help to understand their thermoresponsive gelation mechanism, hydration structure, polymer-polymer & polymer-water interactions which may prove beneficial for pharmaceutical and biomedicine industries. |