Cyclodextrins and α-cyclodextrin

Introduction

Cyclodextrins are classified according to the number of glucopyranose units in their structure. Therefore, when the cyclodextrin molecule has six glucopyranose units, the denomination is α-cyclodextrin. Seven and eight units of glucopyranose are denominated β-cyclodextrin and γ-cyclodextrin, respectively. Due to the conformation of glucopyranose units bound via α-1,4-glycosidic linkages, these supramolecular structures have incredible features. The inner space of the cyclodextrin molecule is hydrophobic, while the exterior is composed of hydroxyl groups, displaying polar or hydrophilic behaviour. This characteristic allows the formation of inclusion complexes with molecules or groups of the same molecules displaying different polarities. The truncated cone-shaped cyclodextrins possess a hollow, tapered cavity of 0.78 nm in depth, while the top and bottom diameters increase with the number of glucose units.

Due to the hydrophobic cavity, cyclodextrins have inclusion capacity with various substances, ranging from ions to small molecules, oligonucleotides and proteins. β-cyclodextrin possesses the ring with the correct size for various molecules of active agents. Different stoichiometries are possible, but normally, one active agent molecule associates with one cyclodextrin molecule to form reversible complexes.

Its structural characteristics predetermined the application of cyclodextrin as a solubilizer for poorly water-soluble chemicals and as a modifier of drug delivery. Miconazole, itraconazole, piroxicam, indomethacin, digitoxin, naproxen, hydrocortisone, diazepam and pilocarpine are examples of drugs that improved their bioavailability due to enhancement of solubility.

α-CDs

α-cyclodextrins (α-CDs) are cyclic oligosaccharides containing six 1,4-linked d-glucose; due to the glucose chair conformation, CDs are arranged as a hollow truncated cone conferring a hydrophobic character to the CD central cavity relative to the external surface, which is hydrophilic. The α-CDs are enzymatically obtained from starch and its derivates. Functional properties of α-CDs comprising moderate water solubility, tasteless, odourless, thermally stable (up to 200 °C) and stable in alkaline and acid solutions[1].

α-Cyclodextrin (α-CD) is a cyclic oligosaccharide derived from corn (Trade name: Mirafit fbcx, ArtJen Complexus, Windsor, Ontario, Canada). It has been shown to form a stable complex with dietary fat. This complex is resistant to normal lipolytic hydrolysis by lipases and thereby reduces the absorption and bioavailability of dietary fat. In addition, the fiber–fat complex does not appear accessible to the human gut flora and, therefore, does not lead to the gastrointestinal side effects associated with weight loss products that cause fat malabsorption. This fiber–fat complex is then excreted in the stool intact. Other weight loss products that inhibit lipase secretion allow free, uncomplexed dietary fats to pass through the digestive system. This leads to steatorrhea (oily stool) and bowel incontinence. In healthy human subjects, α-CD was able to reduce the glucose response (incremental area under the curve) to a test meal containing 50 g carbohydrate without affecting the insulin response. The lowered glycemic response and the lipid binding properties of α-CD suggest that this soluble fiber may be useful in individuals with dyslipidemia, type 2 diabetes and metabolic syndrome[2].

References

[1] Kevin B. Comerford. “The Beneficial Effects α-Cyclodextrin on Blood Lipids and Weight Loss in Healthy Humans.” Obesity 19 6 (2012): 1200–1204.

[2] Lytle Kelli A . “The Soluble Fiber α-Cyclodextrin Does Not Increase the Fecal Losses of Dietary Fat in Adults—A Double-Blind, Randomized, Placebo-Controlled, Crossover Trial.” Journal of Nutrition 148 9 (2018): Pages 1421-1425.