Biomaterial Database

Liposome encapsulated polyethylenimine/ODN polyplexes for brain targeting. 2009

Young Tag Ko, and Raktima Bhattacharya, and Ulrich Bickel

Department of Pharmaceutical Sciences, Texas Tech University Health Science Center, Amarillo, 79106, USA.

Despite high in vitro transfection efficiency, the use of the cationic polymer polyethylenimine (PEI) for systemic application is limited due to its rapid blood clearance and accumulation by RES sites upon intravenous administration of PEI/DNA polyplexes. Therefore, it is important to improve the properties of the PEI/DNA complex with respect to extending the systemic circulation time and suppression of RES uptake. In this study, we applied PEGylated liposome technology for systemic delivery of PEI polyplex of oligodeoxynucleotides (ODN), based on encapsulation of the PEI/ODN polyplexes into PEGylated liposomes. The PEI/ODN polyplex was prepared with a low-branched PEI with MW 2.7 kDa and 20-mer double stranded ODN and was then entrapped into PEGylated liposomes with 95% loading efficiency, leading to a virus-like structure with approximately 130 nm diameter. The PEG-stabilized liposome (PSL) entrapping PEI/ODN polyplexes remained stable in the presence of serum. Upon intravenous administration, the DNA in the PSL was cleared from systemic circulation at a significantly slower rate as compared to the naked PEI/ODN complex. Furthermore, targeting of the PSL with antibody specific to transferrin receptor redirected biodistribution of the entrapped ODN, leading to significant accumulation in the targeted organ, i.e. brain. Encapsulation of the PEI/ODN polyplexes within a long-circulating liposome provided a promising ODN delivery system for in vivo application.

UI	MeSH Term	Description	Entries
D007097	Imines	Organic compounds containing a carbon-nitrogen double bond where a NITROGEN atom can be attached to HYDROGEN or an alkyl or aryl group.	Imine
D008081	Liposomes	Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.	Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D008297	Male		Males
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009838	Oligodeoxyribonucleotides	A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.	Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D010316	Particle Size	Relating to the size of solids.	Particle Sizes,Size, Particle,Sizes, Particle
D010714	Phosphatidylethanolamines	Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids.	Cephalin,Cephalins,Ethanolamine Phosphoglyceride,Ethanolamine Phosphoglycerides,Ethanolamineglycerophospholipids,Phosphoglyceride, Ethanolamine,Phosphoglycerides, Ethanolamine
D010743	Phospholipids	Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.	Phosphatides,Phospholipid
D011092	Polyethylene Glycols	Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.	Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D011095	Polyethylenes	Synthetic thermoplastics that are tough, flexible, inert, and resistant to chemicals and electrical current. They are often used as biocompatible materials for prostheses and implants.	Ethylene Polymers,Ethene Homopolymers,Homopolymers, Ethene,Polymers, Ethylene