New MultiPEG-conjugated theophylline derivatives: synthesis and pharmacological evaluations.
The successful conjugation of active theophylline molecules to two new multifunctional high-molecular weight poly(ethylene glycol) derivatives (MultiPEG) and their pharmacokinetic evaluations are reported. The drug loading was increased up to six times in comparison with commercial PEG of the same molecular weight. A clear increase of the time of persistence within the body and a concomitant improvement of the overall pharmacokinetic properties of those prodrugs were also observed. These studies sustain the use of these new PEG-based polymeric supports as a valuable alternative for an effective drug delivery system.
Zacchigna
Marina
M
Department of Pharmaceutical Science, University of Trieste, Piazzale Europa, 1, 34127 Trieste, Italy. zacchign@units.it
Di Luca
Gabriella
G
Cateni
Francesca
F
Maurich
Venerando
V
Ballico
Maurizio
M
Bonora
Gian Maria
GM
Drioli
Sara
S
D000818:Animals; D019540:Area Under Curve; D001711:Biotransformation; D001993:Bronchodilator Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013806:Theophylline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*
D001993:Bronchodilator Agents; D011092:Polyethylene Glycols; D013806:Theophylline