Cyclodextrins and their uses: a review

Cyclodextrin Drug Carrier Systems.

Cyclodextrins as pharmaceutical solubilizers.

Cyclodextrins are cyclic oligomers of glucose that can form water-soluble inclusion complexes with small molecules and portions of large compounds. These biocompatible, cyclic oligosaccharides do not elicit immune responses and have low toxicities in animals and humans. Cyclodextrins are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current cyclodextrin-based therapeutics are described and possible future applications discussed. Cyclodextrin-containing polymers are reviewed and their use in drug delivery presented. Of specific interest is the use of cyclodextrin-containing polymers to provide unique capabilities for the delivery of nucleic acids.

Cyclodextrin-based pharmaceutics: past, present and future

Cyclodextrins and their pharmaceutical applications.

https://onlinelibrary.wiley.com/doi/pdf/10.1021/js960213f

Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation

Improvement of Nasal Bioavailability of Luteinizing Hormone-Releasing Hormone Agonist, Buserelin, by Cyclodextrin Derivatives in Rats

Maltosyl-beta-cyclodextrin (G2-beta-CyD) suppressed the aggregation of insulin in neutral solution, while the sulfate of beta-CyD (S-beta-CyD) accelerated the aggregation. On the other hand, the sulfobutyl ether of beta-CyD (SBE-beta-CyD) showed varying effects on insulin aggregation, depending on the degree of substitution of the sulfobutyl group: i.e., the inhibition at relatively low substitution and acceleration at higher substitution. Differential scanning calorimetric studies indicate that the self-association of insulin stabilized the native conformation of the peptide, as indicated by an increase in the mean unfolding temperature (Tm). G2-beta-CyD and SBE-beta-CyD decreased the Tm value of insulin oligomers, while S-beta-CyD increased the Tm value. 1H-Nuclear magnetic resonance spectroscopic studies suggest that G2-beta-CyD includes accessible hydrophobic side chains of insulin within the CyD cavity, and hence perturbs the intermolecular hydrophobic contacts between aromatic side chains across the monomer-monomer interfaces. By contrast, the electrostatic interaction between the positive charges of insulin and the concentrated negative charges of the sulfate and sulfonate groups of the anionic beta-CyDs seems to be more of a factor than the inclusion effects. These results suggest proper use of the CyD derivatives could be effective in designing rapid or long-acting insulin preparations.

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Varying effects of cyclodextrin derivatives on aggregation and thermal behavior of insulin in aqueous solution

The potential use of three 2-hydroxypropyl ether derivatives of cyclodextrins (HP-α-, HP-β- and HP-γ-CyDs) as biocompatible solubilizers and stabilizers and stabilizers for oleic acid, a lipophilic absorption enhancer, was assessed in the nasal absorption of buserelin, an agonist of luteinizing hormone-releasing hormone, in rats. HP-CyDs increased the aqueous solubility of oleic acid and protected it against oxidation through the formation of inclusion complexes with the efficacy increasing in the order : HP-γ-CyD«HP-α-CyD<HP-β-CyD. The bend structure due to a cis-double bond halfway along the acyl chain of oleic acid provided a better fit into the cavity of HP-β-CyD, in which the double bond appears to be buried, and hence becomes less susceptible to oxidation. The rate and extent of nasal bioavailability of buserelin were remarkably increased by coadministration of oleic acid and HP-β-CyD, compared with the sole use of the enhancer. This enhancement was ascribable to the lowering of both the enzymatic and physical barriers of the nasal epithelium to the peptide, probably through the facilitated transmucosal penetration of oleic acid solubilized in HP-β-CyD.

Enhanced nasal delivery of luteinizing hormone releasing hormone agonist buserelin by oleic acid solubilized and stabilized in hydroxypropyl-β- cyclodextrin

Tetsumi Irie

Papers

Cyclodextrin Drug Carrier Systems.

Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation

Improvement of Nasal Bioavailability of Luteinizing Hormone-Releasing Hormone Agonist, Buserelin, by Cyclodextrin Derivatives in Rats

Varying effects of cyclodextrin derivatives on aggregation and thermal behavior of insulin in aqueous solution

Enhanced nasal delivery of luteinizing hormone releasing hormone agonist buserelin by oleic acid solubilized and stabilized in hydroxypropyl-β- cyclodextrin