Novel polymer-DNA hybrid polymeric micelles composed of hydrophobic poly(D,L-lactic-co-glycolic acid) and hydrophilic oligonucleotides.
Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) was chemically conjugated to oligonucleotide (ODN) to form an amphiphatic structure which is similar to an A-B type block copolymer. A terminal end of PLGA was activated and reacted with primary amine-terminated ODN. The ODN/PLGA conjugates self-assembled in aqueous solution to form a micellar structure by serving PLGA segments as a hydrophobic core and ODN segments as a surrounding hydrophilic corona. Critical micelle concentration was determined by a spectroflurometric method. Atomic force microscopic observation revealed that the micelle size was around 80 nm. These micelles could release ODN in a sustained manner by controlled degradation of hydrophobic PLGA chains. Compared to unconjugated ODN, the ODN/PLGA micelles could be more efficiently transported within cells, presumably by endocytosis. This study proposes a potential delivery method of ODN into cells by forming hybrid ODN/PLGA micelles.
Jeong
J H
JH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea.
Park
T G
TG
D016475:3T3 Cells; D000818:Animals; D001673:Biodegradation, Environmental; D001692:Biological Transport; D016503:Drug Delivery Systems; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008823:Micelles; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000737:chemistry; D012235:Rhodamines; D012995:Solubility
D008823:Micelles; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D011355:Prodrugs; D012235:Rhodamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid