Physicochemical properties of liposomes incorporating hydrochlorothiazide and chlorothiazide

In an attempt to study the effect of hydrophobic drugs on liposome properti es, multilamellar liposomes (MLV) consisting of phosphatidylcholine (PC) an d incorporating chlorothiazide (CT) or hydrochlorothiazide (HCT), were prep ared and characterized, Liposome size, surface charge, stability (in buffer , plasma and sodium cholate) and calcium-induced aggregation were studied f or drug-incorporating liposomes and empty liposomes for comparison. Results show that drug incorporation affects liposome size, z-potential and stabil ity in presence of buffer and plasma proteins. Indeed, drug-incorporating l iposomes are slightly larger and have a negative surface charge, which incr eases with the amount of drug incorporated in the lipid membrane. The membr ane integrity of drug incorporating liposomes (in absence and presence of p lasma proteins) is significantly higher when compared with that of empty li posomes (for both drugs studied). On the contrary, vesicle membrane integri ty in presence of sodium cholate and calcium induced vesicle aggregation, a re not affected by drug incorporation. Leakage of thiazides from liposomes was demonstrated to be induced by dilution. Low amounts of thiazides (aroun d 10-15%) are released when lipid concentration is over 0.1 mM, while furth er dilution increased drug leakage exponentially. Concluding, results demon strate that the presence of HCT or CT in Liposome membranes has a significa nt effect on main vesicle properties, which are known to influence vesicle targeting ability. Thereby, it is very interesting to continue studies in t his respect, especially with more lipophilic drugs.