Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and improve their physicochemical properties without molecular modifications. The stoichiometry of drug/CD complexes is most frequently 1:1. However, natural CDs have a tendency to self-assemble and form aggregates in aqueous media. CD aggregation can limit their solubility. Through derivative formation, it is possible to enhance their solubility and complexation capacity, but this depends on the type of substituent and degree of substitution. Formation of water-soluble drug/CD complexes can increase drug permeation through biological membranes. To maximize drug permeation the amount of added CD into pharmaceutical preparation has to be optimized. However, solubility of CDs, especially that of natural CDs, is affected by the complex formation. The presence of pharmaceutical excipients, such as water-soluble polymers, preservatives, and surfactants, can influence the solubilizing abilities of CDs, but this depends on the excipients’ physicochemical properties. The competitive CD complexation of drugs and excipients has to be considered during formulation studies.

Cyclodextrins (CDs) are recognized as promising pharmaceutical excipients due to their unique ability to form watersoluble inclusion complexes with various poorly soluble compounds. The numerous investigations on CDs and their use in nanomedicine have received considerable attention in the last three decades, leading to the rapid development of new CD-containing formulations that significantly facilitate targeted drug delivery and controlled drug release, with consequent improvements in drug bioavailability. This MiniReview highlights the efficacy and recent uses of CDs for non-invasive drug delivery. Using ophthalmic and nasal drug delivery as examples, an overview of chemical properties, mechanisms of CDs on drug solubilization, stabilization and permeation, along with their toxicological profiles relevant to nasal and ocular administration, are provided and discussed. The recent development and application of CD-based nanocarrier systems for targeted drug delivery are summarized.Cyclodextrins (CDs) are natural cyclic oligosaccharides that are produced by enzymatic degradation of starch. There are three native CDs designated aCD, bCD and cCD, which are composed of 6, 7 and 8 D-glucopyranose units linked by a-(1, 4) glycosidic, respectively [1]. The molecules are commonly described as truncated cone, bucket-like or donut-shaped, with a hydrophilic outer surface and a relatively hydrophobic inner cavity that allows entrapment of small hydrophobic drug molecules or hydrophobic moieties of larger molecules [2], thereby providing drugs with new physicochemical characteristics without altering their intrinsic properties. Table 1 summarizes the characteristics of different CDs. Natural CDs are preferred for complexation; however, their usability is limited by the small cavity size of aCD, poor aqueous solubility of bCD and low productivity of cCD [3]. Derivatized CDs can be obtained by substituting their hydroxyl groups with desired functional moieties. Methyl-(MebCD and MecCD) [4,5], hydroxypropyl-(HPaCD, HPbCD and HPcCD) [6][7][8] and sulphobutylether (SEBbCD) derivatives [9] are frequently found in pharmaceutical products and have improved solubility and inclusion capacity over natural CDs. Pharmaceutical applications of both natural CDs and their derivatives are common when drug/CD complexes are used to increase drug solubility, improve organoleptic properties [10], enhance drug permeation [11] and increase drug stability, resulting in increased product shelf-life and drug bioavailability [12]. In addition, spontaneous self-assembly of drug/CD complexes into aggregates can lead to innovative drug delivery systems, such as CD-containing liposomes and microspheres as well as microand nanoparticles [13]. Polymerized CDs (e.g. Epi-aCD and Epi-bCD) have also been synthesized to enhance the selfassembly ability of CDs, and to strengthen their interactions with drugs and biological membranes [14]. Compared with other pharmaceutical excipients, CDs have been shown to reduce the toxicity of several drugs and are...

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In this present study cyclodextrin (CD)-poloxamer aggregates were characterized and developed as ophthalmic drug carriers. The combined effect of γCD/2-hydroxypropyl-γCD (HPγCD) mixtures and poloxamer on solubilization and permeability of two model drugs, dexamethasone (Dex) and amphotericin B (AmB), was investigated. The CD-poloxamer interaction and complex aggregation were examined by (1)H nuclear magnetic resonance ((1)H-NMR), their solubilizing ability by high-performance liquid chromatography, and their particle size determined by dynamic light scattering and transmission electron microscopy. Formulations containing either 1.5% w/v Dex or 0.15% w/v AmB in eye drop suspensions containing various γCD/HPγCD ratios and poloxamer 407 (P407) were prepared. The solubility of the drugs, surface tension and hemolytic effect of the eye drops and drug permeation from selected formulations were determined. The (1)H-NMR study showed that P407 formed inclusion complex with CDs by inserting its poly(propylene oxide) segment into the CD cavity. P407 and γCD interacted with each other to form nanosized aggregates, and the observed concentration of dissolved γCD and P407 progressively decreased with increasing γCD and P407 concentrations. Including a high proportion of HPγCD improved the drug solubilization and reduced the hemolytic effect. The surface tension of the formulations decreased with increasing P407 concentration. Furthermore, increasing P407 content in the formulations enhanced formation of complex aggregates with consequent slower drug release. It was concluded that the drug/γCD/HPγCD complex was stabilized by P407 through formation of multi-component aggregates. Thus, CD-poloxamer aggregates are self-assembled nanocarriers from which drug delivery characteristics can be adjusted by changing the γCD/HPγCD/P407 ratios.