Studies of controlled release of drugs from nanoliposomes

Liposomes can potentially serve as carrier systems for controlled delivery of drugs. The main goal of this project was to study and understand the effects of liposomal structures on controlled release of drugs. The drugs chosen for this project falls into various categories such as the weak base (model drug, lidocaine salt and base form), zwitterionic (ciprofloxacin hydrochloride) and lipophilic (latanoprost) that are currently approved for treatment of various ocular diseases. An effort was made to systematically evaluate the release of drugs from liposomal nanocarriers with various parameters such as drug/lipid mole ratios, medium pH, cholesterol concentrations and physicochemical properties of the drug and lipid. We achieved high drug loading concentrations of hydrophilic and hydrophobic drugs in nano sized liposomes by active and passive loading strategies with good size stability on storage and release. The release rates obtained were unique for each drug type and found to be dependent on the different parameters evaluated. A mechanism for release of a model drug, lidocaine in its salt and base form was proposed and found to be driven by diffusion of the neutral form of the drug through the bilayer. A concentration dependent release of ciprofloxacin hydrochloride from liposomes was observed. Liposomal formulations which contained cholesterol, an additive, demonstrated sustained release for over 30 days possibly due to hydrogen bond formation between the drug and cholesterol.Doctor of Philosophy (MSE