THERAPEUTIC AND DIAGNOSTIC UTILITY OF CYCLODEXTRIN DERIVATIVES

Lajos Szente

CycloLab Cyclodexrin Research and Development Laboratory Ltd., Illatos út 7. 1097 Budapest, Hungary

Abstract

Cyclodextrins (CDs) have long been known and used as functional excipients in different pharmaceutical dosage forms. The last 35 years in CD technology has witnessed the successful uses of CDs for stabilisation, solubilisation and bioavailability improvement of poorly soluble APIs. (1) At present more than 40, CD-enabled human pharmaceutical products are on the market.

Recently, the therapeutic uses of “empty” non-occupied CD nano cavities have been emphasized. The first such application was published in 1983, where empty CDs were used to selectively remove toxic retionoids from the systemic circulation after A vitamin intoxication. (2) Based on this recognition, Organon-Biosciences started a program aiming at selective removal of neuromuscular blocking agent from anesthetized patients by using a taylor-made CD that binds target API. These efforts resulted in the approval of a uniquely modified gammaCD nanocavity. The fist cyclodextrin as a drug, a selective binding agent was marketed recently in USA, EU and Japan under the tradename Bridion® by Merck, Co.

The safe and potent solubilizing excipient, 2-hydroxypropyl-b-CD (HPBCD) listed in both the US and EU Pharmacopoeias, has received Orphan Drug designation, due to its selective cholesterol binding property. It has been established that HPBCD improves the clinical status of patients suffering from a uncurable, lysosomal storage disease called Nieman-Pick-Type C (NPC). Soon, after clinical trials, in 2010, first US FDA, later EU granted Orphan drug designation for HPBCD to treat NPC. Currently more than 20 patients world-wide are treated with promising results.

Similar lipid complexing properties were recently used to apply HPBCD as a lead drug candidate for two orphan kidney indications (Focal Segmental Glomerulosclerosis and Alport Syndrome) by Variant Pharmaceuticals. (3)

A number of further therapeutic applications of CDs themselves are expected to come.

A unique, diagnostic application of a CD has been developed and the method marketed by Oxford Nanopore Ltd for automatized DNA sequencing. A bacterial protein nanopore is combined by a CD as analyte-recognizing adapter sensor that enables quick, reliable and cheap DNA sequencing. (4) The devices named MinON®, SmigdION® are currently in practical use.

Keywords: Cyclodextrins, excipients, therapeutic, lipid, nanopore.

REFERENCES

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WO2013155485 A2 Method of Using cyclodextrin
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