A novel micellar PEGylated hyperbranched polyester as a prospective drug delivery system for paclitaxel.
A hyperbranched aliphatic polyester has been functionalized with PEG chains to afford a novel water-soluble BH40-PEG polymer which exhibits unimolecular micellar properties, and is therefore appropriate for application as a drug-delivery system. The solubility of the anticancer drug paclitaxel was enhanced by a factor of 35, 110, 230, and 355 in aqueous solutions of BH40-PEG of 10, 30, 60, and 90 mg x mL(-1), respectively. More than 50% of the drug is released at a steady rate and release is almost complete within 10 h. The toxicity of BH40-PEG was assessed in vitro with A549 human lung carcinoma cells and found to be nontoxic for 3 h incubation up to a 1.75 mg x mL(-1) concentration while LD50 was 3.5 mg x mL(-1). Finally, it was efficiently internalized in cells, primarily in the absence of foetal bovine serum, while confocal microscopy revealed the preferential localization of the compound in cell nuclei. [Figure: see text].
Kontoyianni
Christina
C
Institute of Physical Chemistry, NCSR "Demokritos", 15310 Aghia Paraskevi, Attiki, Greece.
Sideratou
Zili
Z
Theodossiou
Theodossis
T
Tziveleka
Leto-Aikaterini
LA
Tsiourvas
Dimitris
D
Paleos
Constantinos M
CM
D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage*; D011091:Polyesters / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D011092:Polyethylene Glycols; D012995:Solubility
D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols; D017239:Paclitaxel