Since its discovery in the late 19th century, cyclodextrin (CD) has been mainly used as an excipient due to its ability to form inclusion complexes with various molecules. Essentially, CDs were regarded as inert materials. However, it has been found that some CD molecules are not so inert and instead have some biological activity according to other research advances in CD. Therefore, certain CD molecules can be used as active pharmaceutical ingredients for specific medical applications in the treatment of several human ailments, such as infectious ailments, cardiovascular dysfunction, and metabolic diseases [1].
Pharmacological Activities of CDs
The main pharmacological activities of CDs are antiviral and antiparasitic activities. The former is manifested through the property of CD binding to cholesterol, while the latter is mainly due to the ability of CD to inhibit parasite replication.
Many CDs exhibit antiviral abilities primarily through their ability to bind to cholesterol, which is the target of human immunodeficiency virus (HIV) treatment. Taking 2-hydroxypropyl-β-cyclodextrin (HPβCD) as an example, the literature reports that it has the ability to block HIV virus transmission in mice. It is able to remove some cholesterol molecules from the host cell membrane, making them less susceptible to viral infection [2]. It also removes cholesterol from viral particles, thereby destroying HIV and simian immunodeficiency virus (SIV).
CD exhibits some antiparasitic activity against Leishmania donovani, Cryptosporidium parvum, and malaria parasites, and therefore may be used against leishmaniasis, cryptosporidiosis, and malaria, as shown in Table 1.
Table 1. Anti-parasitic instances of CD
| Parasites | Instances |
| Leishmania donovani | Infection with Leishmania donovani causes leishmaniasis. Studies have reported that randomly methylated β-CD (RAMEB) can effectively reduce the infectivity of Leishmania donovani and its ability to infect host immune cells [3,4]. |
| Cryptosporidium parvum | Enteric infection caused by the parasite Cryptosporidium parvum is known as cryptosporidiosis. Two native CDs, α-CD and β-CD, have proven to be very useful in controlling cryptosporidiosis as they reduce oocyst viability [5]. |
| Malaria parasites | Protozoan parasites of the genus Plasmodium cause malaria and threaten human life. The sulphated anionic derivatives of parent CDs (α-, β- and γ-CDs) served as antimalarial agents to inhibit the replication of Plasmodium falciparum, and their activities are primarily related to the degree of CD substitution. The sodium salt of a poly-sulphated β-CD containing 16.9 sulphate groups showed the best activity [6]. |
Potential Drugs Based on CDs
Based on the antiviral and antiparasitic pharmacological activities exhibited, CD can be used as an active ingredient to discover potential drug candidates, such as HIV vaccines or antiparasitic agents.
- HIV vaccines
Since HPβCD exhibits HIV antiviral activity in mice, research on HIV vaccines based on HPβCD has attracted a lot of attention. However, further research is still needed to verify the effectiveness of HPβCD in animal models closer to humans, thereby laying the foundation for developing innovative HIV vaccines. - Antiparasitic agents
Due to the antiparasitic activity of CDs, certain CD molecules may serve as drug candidates for the treatment of diseases caused by parasites. For example, HPβCD has been approved for use in injectable formulations and RAMEB has been proposed as a new leishmanicidal drug. α-CD has been used to help improve symptoms of diarrhea, dehydration and infection caused by cryptosporidiosis [1]. 16.9-sulfated-β-CD may be a promising new lead drug for malaria treatment.
Alfa Chemistry is dedicated to the manufacture of CDs. We offer high-quality native CDs, CD derivatives, and CD inclusion complexes. We have strong supply capabilities and can provide products at the kilogram level. Please feel free to contact us and we will serve you wholeheartedly.
References
- Braga, S. S. Cyclodextrins: Emerging Medicines of the New Millennium. Biomolecules. 2019, 9(12): 801.
- Liao, Z.; et al. Lipid rafts and HIV pathogenesis: Host membrane cholesterol is required for infection by HIV type 1. Aids Res. Hum. Retrov. 2001, 17: 1009–1019.
- Pucadyil, T. J.; et al. Cholesterol is required for Leishmania donovani infection: Implications in leishmaniasis. Mol. Biochem. Parasitol. 2004, 133: 45–152.
- Rodríguez, N. E.; et al. Role of caveolae in Leishmania chagasi phagocytosis and intracellular survival in macrophages. Cell. Microbiol. 2006, 8: 1106–1120.
- Castro-Hermida, J.A.; et al. In vitro activity on Cryptosporidium parvum oocyst of different drugs with recognized anticryptosporidial efficacy. Revue Méd. Vét. 2004, 155: 453–456.
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