Improved formulations of antisense oligodeoxynucleotides using wrapped liposomes

Area of Science:

• Biotechnology
• Drug Delivery
• Nanomedicine

Background:

• Lipid-based nanoparticles are crucial for drug delivery.
• Wrapped liposomes (WL) previously enhanced plasma circulation of dextran fluorescein.
• Antisense oligodeoxynucleotides (ODN) require effective delivery systems.

Purpose of the Study:

• To evaluate wrapped liposomes (WL) for formulating fluorescence-labeled phosphorothioated ODN (F-ODN).
• To assess the in vitro stability and in vivo pharmacokinetic properties of F-ODN loaded WL.
• To determine the tumor targeting efficiency of WL for F-ODN.

Main Methods:

• Preparation of WL encapsulating F-ODN/cationic lipid complexes.
• In vitro stability assessment of the formulated WL.
• Intravenous administration of free F-ODN, naked complexes, and WL to mice.
• Pharmacokinetic studies measuring blood concentrations of F-ODN.
• Biodistribution studies in a Caki-1 xenograft tumor model.

Main Results:

• WL formulations were successfully prepared and demonstrated in vitro stability.
• WL significantly increased F-ODN plasma half-life compared to free or naked F-ODN.
• Intravenous administration of WL resulted in sustained high blood concentrations of F-ODN.
• WL delivered 13-fold more F-ODN to the tumor site compared to free F-ODN in a xenograft model.

Conclusions:

• Wrapped liposomes (WL) represent a promising formulation strategy for antisense oligodeoxynucleotides (ODN).
• WL enhance the stability and prolong the circulation time of F-ODN.
• This technology significantly improves F-ODN tumor accumulation, suggesting potential for targeted cancer therapy.