In vivo efficacy of enabling formulations based on hydroxypropyl‐β‐cyclodextrins, micellar preparation, and liposomes for the lipophilic cannabinoid CB2 agonist, MDA7. Issue 2 (28th November 2012)

• Record Type: Journal Article
• Authors: Astruc‐Diaz, Fanny; Mcdaniel, Steven W.; Xu, Jijun J.; Parola, Stéphane; Brown, David L.; Naguib, Mohamed; Diaz, Philippe
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 2(2013:Feb.)
• Page Start: 352
• Page End: 364
• Publication Date: 2012-11-28
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23393
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Enabling formulations based on hydroxypropyl‐β‐cyclodextrins (HPβCD), micellar preparation, and liposomes have been designed to deliver the racemic mixture of a lipophilic cannabinoid type 2 agonist, MDA7. The antiallodynic effects of MDA7 formulated in these three different systems were compared after intravenous (i.v.) administration in rats. Stoichiometry of the inclusion complex formed by MDA7 in HPβCD was determined by continuous variation plot, electrospray ionization–mass spectrometry (ESI–MS) analysis, phase solubility, and nuclear magnetic resonance studies and indicate formation of exclusively 1:1 adduct. Morphology and particle sizes determined by dynamic light scattering and transmission electron microscopy show the presence of a homogeneous population of closed round‐shaped oligolamellar MDA7 containing liposomes, with an average size of 118 nm [polydispersity index (PDI) 0.03]. Monodisperse micelles exhibited an average size of 14 nm (PDI 0.09). HPβCD‐based formulation administrated <italic>in vivo</italic> was composed of two discrete particles populations with a narrow size distribution of 3 nm (PDI 0.04) and 510 nm (PDI 0.02). HPβCD‐based formulation dramatically improved antiallodynic effect of MDA7 in comparison with the liposomes preparation. Through inclusion complexation and possibly formation of aggregates, HPβCD can enhance the aqueous solubility of lipophilic drugs, thereby improving their bioavailability for i.v. administration. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:352–364, 2013</p> </abstract>