Synthesis and pharmacological evaluation of a new targeted drug carrier system: beta-cyclodextrin coupled to oxytocin.
Beta-cyclodextrin (beta-CD) was monofunctionalized into its carboxylic derivative and then conjugated to the N-side of oxytocin (OT), a nonapeptide involved in human behavior and myometrium contraction. On isolated rat myometrium, this conjugate (beta-CD-OT) partly preserves the contracting activity of OT (EC(50) = 0.40 microM vs 1.7 nM). Moreover, the contraction induced frequency is also lowered by beta-CD-OT. This novel hydrophilic targeted carrier could form a host-guest complex with prostaglandins and their derivatives used as labor inducers or with anticancer drugs used in cervix and endometrial cancer. This strategy can improve the solubility, the stability, and/or the biological activity of these drugs as well as reducing their side-effects.
Bertolla
Carine
C
Drug Design and Discovery Center, University of Namur, FUNDP, 61 rue de Bruxelles, 5000 Namur, Belgium.
Rolin
Stéphanie
S
Evrard
Brigitte
B
Pochet
Lionel
L
Masereel
Bernard
B
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009215:Myometrium / Q000166:cytology / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology*; D010121:Oxytocin / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*; D047392:beta-Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*
D004337:Drug Carriers; D010120:Oxytocics; D047392:beta-Cyclodextrins; C529307:mono-6-deoxy-6-oxytocinyl-beta-cyclodextrin 5; D010121:Oxytocin; C031215:betadex