Polycaprolactone-b-poly(ethylene oxide) block copolymer micelles as a novel drug delivery vehicle for neurotrophic agents FK506 and L-685,818.
Micelles formed from polycaprolactone-b-poly(ethylene oxide) (PCL-b-PEO) diblock copolymers were investigated as a novel drug delivery system. The affinity of the micelles for hydrophobic solubilizates was assayed by determining the partition coefficient for the lipophilic compound, pyrene, between the micelles and water; the partition coefficient was found to be on the order of 10(2). The Trypan blue and Alamar blue survival assays were used to assess the in vitro biocompatibility of the micelles with PC 12 cells, MCF-7 breast cancer cells, and primary cultures of human microglia, astrocytes, and cortical neurons. The micelles were then studied as a delivery vehicle for the neurotrophic agents FK506 and L-685,818 in PC 12 cell cultures. In both cases, the micelle-incorporated drugs, in the presence of nerve growth factor (5 ng/mL), were able to promote the degree of differentiation of the PC 12 rat pheochromocytoma cells.
Allen
C
C
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal P.Q, Canada H3A 2K6.
Yu
Y
Y
Maysinger
D
D
Eisenberg
A
A
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D005453:Fluorescence; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007783:Lactones / Q000627:therapeutic use*; D008823:Micelles; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells; D010316:Particle Size; D011108:Polymers / Q000627:therapeutic use*; D011721:Pyrenes / Q000378:metabolism; D051381:Rats; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D007783:Lactones; D008823:Micelles; D009414:Nerve Growth Factors; D011108:Polymers; D011721:Pyrenes; C076383:L 685818; C030984:pyrene; D016559:Tacrolimus