Pharmacokinetics of oligodeoxynucleotides encapsulated in liposomes: effect of lipid composition and preparation method

1. The effect of the method employed to prepare liposomes and their lipid c omposition were evaluated in terms of the encapsulation efficiency and phar macokinetic features of two oligodeoxynucleotides of a 21 mer: the normal ( N-Odn) and the phosphorothioate (S-Odn) oligodeoxynucleotide. 2. Liposomes were prepared by the classical method of multilamellar vesicle s (MV) and by the dehydration-rehydration method (DR). Two lipid mixtures w ere used to prepare liposomes-the predominant lipid being phosphatidylcholi ne (PC) and sphingomyelin (SM) respectively. 3. The DR method for liposome preparation provided the highest encapsulatio n efficiency, regardless of liposome lip id composition and the type of oli go deoxynucleotide involved (N-Odn or S-Odn). 4. The pharmacokinetics of free and liposome encapsulated oligodeoxynucleot ides was studied in mouse following i.v. administration. Liposome encapsula ted oligodeoxynucleotides exhibited a significantly lower plasma clearance and longer half-life and residence time than free oligodeoxynucleotides. Th e method used to obtain the liposomes affected plasma clearance, which was lower for liposomes elaborated by the DR method than for liposomes prepared with the MV method. The use of S-Odn in place of N-Odn decreased the plasm a clearance of oligodeoxynucleotide when administered encapsulated in lipos omes, regardless of the lipid composition and method used to obtain the lip osomes.