Hydrophobic drug delivery by self-assembling triblock copolymer-derived nanospheres.
We describe the synthesis and characterization of a family of biocompatible ABA-triblock copolymers that comprised of hydrophilic A-blocks of poly(ethylene glycol) and hydrophobic B-blocks of oligomers of suberic acid and desaminotyrosyl-tyrosine esters. The triblock copolymers spontaneously self-assemble in aqueous solution into nanospheres, with hydrodynamic diameters between 40 and 70 nm, that do not dissociate under chromatographic and ultracentrifugation conditions. These nanospheres form strong complexes with hydrophobic molecules, including the fluorescent dye 5-dodecanoylaminofluorescein (DAF) and the antitumor drug, paclitaxel, but not with hydrophilic molecules such as fluorescein and Oregon Green. The nanosphere-paclitaxel complexes retain in vitro the high antiproliferative activity of paclitaxel, demonstrating that these nanospheres may be useful for delivery of the hydrophobic drugs.
Sheihet
Larisa
L
Department of Chemistry and Chemical Biology and New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Dubin
Robert A
RA
Devore
David
D
Kohn
Joachim
J
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry; D002210:Caprylates / Q000737:chemistry; D002845:Chromatography; D002850:Chromatography, Gel; D003998:Dicarboxylic Acids / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004952:Esters; D019793:Fluorescein / Q000494:pharmacology; D005452:Fluoresceins / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D008970:Molecular Weight; D036103:Nanotechnology; D043942:Nanotubes / Q000737:chemistry; D009369:Neoplasms / Q000628:therapy; D017239:Paclitaxel / Q000494:pharmacology; D010710:Phosphates / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry; D014461:Ultracentrifugation
C503505:5-dodecanoylaminofluorescein; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D002210:Caprylates; D003998:Dicarboxylic Acids; D004952:Esters; D005452:Fluoresceins; D010710:Phosphates; D011108:Polymers; D011092:Polyethylene Glycols; D014443:Tyrosine; C005738:suberic acid; D017239:Paclitaxel; D019793:Fluorescein