Effects of ethylene glycol-based graft, star-shaped, and dendritic polymers on solubilization and controlled release of paclitaxel.
New methods and pharmaceutical compositions were developed to increase the aqueous solubility of paclitaxel (PTX), a poorly water-soluble drug. Graft and star-shaped graft polymers consisting of poly(ethylene glycol) (PEG400) graft chains increased the PTX solubility in water by three orders of magnitude. Polyglycerol dendrimers (dendriPGs) dissolved in water at high concentrations without significantly increasing the viscosity and, at 80 wt.%, were found to increase the solubility of PTX 10,000-fold. The solubilized PTX was released from graft polymers, star-shaped graft polymers, and the dendriPGs into the surrounding aqueous solution. The release rate was a function of the star shape and the dendrimer generation. The availability of the new graft, star and dendritic polymers having ethylene glycol units should permit development of novel delivery systems for other poorly water-soluble drugs.
Ooya
Tooru
T
School of Materials Science, Japan Advanced Institute of Science and Technology, Tatsunokuchi, Ishikawa 923-1292, Japan.
Lee
Jaehwi
J
Park
Kinam
K
D000818:Animals; D002417:Cattle; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000493:pharmacokinetics; D019855:Ethylene Glycol / Q000737:chemistry / Q000493:pharmacokinetics*; D005312:Fetal Blood; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D015394:Molecular Structure; D008970:Molecular Weight; D009552:Nikethamide / Q000737:chemistry / Q000493:pharmacokinetics; D017239:Paclitaxel / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility / Q000187:drug effects*; D013997:Time Factors; D014783:Viscosity / Q000187:drug effects; D014867:Water / Q000737:chemistry
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; C450003:poly(ethylene glycol) methacrylate polymer; D014867:Water; D009552:Nikethamide; D011092:Polyethylene Glycols; D019855:Ethylene Glycol; D017239:Paclitaxel; D005990:Glycerol