Send Orders for Reprints to reprints@benthamscience.net 526 Current Topics in Medicinal Chemistry, 2014, 14, 526-541 Progress in Developing Amphiphilic Cyclodextrin-Based Nanodevices for Drug Delivery Josias B.G. Yaméogo 1,3 , Annabelle Gèze 1 , Luc Choisnard 1 , Jean-Luc Putaux 2 , Rasmané Semdé 3 and Denis Wouessidjewe 1,* 1 DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, University of Grenoble, France; 2 CERMAV,CNRS, BP 53, F-38041 Grenoble Cedex 9, France – Affiliated with Université de Grenoble, member of Institut de Chimie Moléculaire de Grenoble and Institut Carnot PolyNat; 3 UFR/SDS, University of Ouagadougou, Burkina Faso Abstract: Nowadays, colloidal drug carriers represent an alternative to solve drug bioavailabily problems. During the past two decades, colloidal drug carriers have proved to improve the therapeutic index of drugs and thus increase their efficacy and/or reduce their toxicity. However, the major challenge in the development of these drug carriers remains the search for materials able to self-organize into stable nanoscale systems. In particular, amphiphilic -, - and -cyclodextrins (CDs), grafted on their secondary or primary side with different aliphatic chains, have been investigated as drug delivery vehicles due to their ability to self-assemble and form various stable colloidal systems such as micellar aggregates, nanoreservoirs or nanoparticles exhibiting a matricial, multilamellar or hexagonal supramolecular organization. These self-assembled CD-based nanodevices show some advantages in terms of stability, good ability to associate lipophilic drugs and good in vivo tolerance. This review focuses on the potential of the structured nanoparticles obtained from non- ionic amphiphilic CDs in drug delivery and targeting. We discuss the synthesis and characterization of the building blocks as well as the preparation and characterization of colloidal particles made from these materials. We also considered some pharmaceutical applications and identified opportunities for an optimum use of this CD-based nanotechnology approach in addressing worldwide priority health problems. Keywords: Amphiphilic cyclodextrins, synthesis, characterization, nanoparticles, drug delivery, bioevaluation. 1. INTRODUCTION Cyclodextrins (CDs) are cyclic oligosaccharides consist- ing of glucopyranose units linked by -(1,4) bonds [1]. CDs are of three types (,  and ), depending on the number of glucopyranose units in the molecule: 6, 7 or 8, respectively. The molecule has a three-dimensional truncated cone struc- ture with small and large sides, called primary and secondary faces, respectively (Fig. 1). Each glucopyranose unit con- tains three hydroxyl groups in positions 2, 3 and 6 (see the arrows in Fig. 1). The hydroxyl at position 6 is located on the primary side whereas the hydroxyls in positions 2 and 3 are on the secondary face. This arrangement results in a polar, hydrophilic external surface and relatively apolar, hydropho- bic nanocavity making CD molecules soluble in aqueous medium with a possibility to accept lipophilic guest mole- cules in their cavity via non-covalent bonds [2-4]. The physicochemical properties of CDs and various chemical potential modifications are of great interest for ap- plications in several domains. The capability of forming in- clusion complexes with hydrophobic guest molecules is par- ticularly interesting for administration of bioactive molecules with poor water solubility. This molecular “encapsulation” confers different physicochemical properties to the guest *Address correspondence to this author at the DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, University of Grenoble, France; Tel.: +33 47635302; Fax: +33 47635322; E-mail: denis.wouessidjewe@ujf-grenoble.fr molecule, including improved stability, apparent aqueous solubility, drug release, bioavailability, and sometimes re- duced toxicity [2-11]. Other types of CD complexes such as non-inclusion complexes are also participating in the solubi- lization of poorly soluble drugs [12-13]. During the past two decades, in a context of emerging nanomedecine, important chemical manipulations were per- formed on CDs to design amphiphilic CD monomers able to form drug nanocarriers with sufficient stability in contact with biological fluids. To the best of our knowledge, even though the native CDs are capable to self-assemble in water, forming various types of aggregates depending on their concentration in wa- ter [14], the weight fraction of CD forming aggregates re- mains very low [13] and never exceeds 1% [15]. Moreover, the stability of such aggregates is not sufficient for parenteral administration. Amphiphilic CDs are a class of monomeric CDs modified by grafting on their basic skeleton chemical groups able to alter their solubility in water and simultane- ously generate a structure with a hydrophilic and a lipophilic parts. Obtaining such amphiphilic CDs involves the grafting of at least a lipophilic entity on the primary and/or secondary side of glucopyranose units. The amphiphilic CDs as build- ing blocks for colloidal constructs can be subdivided into three groups according to their non-ionic, cationic or anionic character. First, the non-ionic amphiphilic CDs mainly comprise the CDs substituted by alkyl chains with different chain lengths. 1873-5294/14 $58.00+.00 © 2014 Bentham Science Publishers