Sufentanil-2-hydroxypropyl-β-cyclodextrin inclusion complex for pain treatment: physicochemical, cytotoxicity, and pharmacological evaluation.
Sufentanil (SUF) is a synthetic analgesic opioid widely used for the management of acute and chronic pain. This drug was complexed with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and the physicochemical characterization, in vitro/ex vivo toxicity assays, and pharmacological evaluation were performed. Differential scanning calorimetry, Fourier transform infrared spectroscopy (FTIR) analysis, and X-ray powder diffraction showed the formation and the morphology of the complex. Nuclear magnetic resonance afforded data regarding inclusion complex stoichiometry (1:1) with an association binding constant (K(a)) value of 515.2 ± 1.2 M(-1) between SUF and HP-β-CD. Complexation with HP-β-CD protected SUF from light exposure and increased its photostability. Release kinetics revealed a decrease in SUF release rate (K(rel) = 7.05 ± 0.52 and 5.61 ± 0.39 min(-1/2) for SUF-HP-β-CD and SUF, respectively) and reduced hemolytic or myotoxic effects after complexation. Time course of tail-flick test showed that the duration of analgesia induced by SUF (150.0 ± 34.6 min) was significantly increased (p < 0.001) after complexation with HP-β-CD (355.7 ± 47.2 min) when injected at the same dose (1 μg kg(-1)), prolonging the duration of analgesia after intramuscular administration and representing an alternative on the development of effective and safe drug-delivery system for opioid analgesics.
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brasil.
Cristiane
C
Volobuef
Carolina M
CM
Moraes
Lázaro A S
LA
Nunes
Cíntia M S
CM
Cereda
Fabiano
F
Yokaichiya
Margareth K K D
MK
Franco
Angélica F A
AF
Braga
Eneida
E
De Paula
Giovana Radomille
GR
Tófoli
Leonardo F
LF
Fraceto
Daniele R
DR
De Araujo
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D010146:Pain / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D017409:Sufentanil / Q000737:chemistry* / Q000494:pharmacology*; D014961:X-Ray Diffraction / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*
D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D017409:Sufentanil