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 composition were evaluated in terms of the encapsulation efficiency and pharmacokinetic 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 vesicles (MV) and by the dehydration-rehydration method (DR). Two lipid mixtures were used to prepare liposomes--the predominant lipid being phosphatidylcholine (PC) and sphingomyelin (SM) respectively. 3. The DR method for liposome preparation provided the highest encapsulation efficiency, regardless of liposome lipid composition and the type of oligodeoxynucleotide involved (N-Odn or S-Odn). 4. The pharmacokinetics of free and liposome encapsulated oligodeoxynucleotides was studied in mouse following i.v. administration. Liposome encapsulated oligodeoxynucleotides exhibited a significantly lower plasma clearance and longer half-life and residence time than free oligodeoxynucleotides. The 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 plasma clearance of oligodeoxynucleotide when administered encapsulated in liposomes, regardless of the lipid composition and method used to obtain the liposomes.
Aliño
S F
SF
Programa Terapia Génica, Facultad de Farmacia, Universidad de Valencia, Spain. alino@uv.es
Crespo
J
J
Tarrasón
G
G
Blaya
C
C
Adán
J
J
Escrig
E
E
Benet
M
M
Crespo
A
A
Peris
J E
JE
Piulats
J
J
D000818:Animals; D004339:Drug Compounding / Q000379:methods*; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013873:Thionucleotides / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
D008055:Lipids; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides