Liposomal delivery of a 30-mer antisense oligodeoxynucleotide to inhibit proopiomelanocortin expression.

An oligodeoxynucleic sequence of 30 bases (30-mer ODN), complementary to a region of beta-endorphin mRNA, was synthesized to have an antisense effect with regard to the expression of this oligopeptide. Following the solid-phase synthesis of the oligodeoxynucleotide, the 30-mer ODN was encapsulated within liposomes to provide a higher resistance against DNases and an improved entrance into cells. The most suitable liposome formulation as a 30-mer ODN carrier consisted of small unilamellar vesicles (50 nm) with an encapsulation capacity of 4.76 microL/micromol. The liposomal formulations containing dipalmitoyl-DL-alpha-phosphatidyl-L-serine presented fusogenic properties, which are of great importance for the delivery of antisense compounds. The antisense activity of 30-mer ODN-loaded liposomes was evaluated by the determination of beta-endorphin levels in AtT-20 cells. The free 30-mer ODN did not provide any lowering of the beta-endorphin production, whereas the liposomally entrapped compound elicited a concentration-dependent inhibition. The inhibition was determined by a sequence-specific binding of the 30-mer ODN with the target mRNA.