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Review of Novel Oral Amphotericin B Formulations for the Treatment of Parasitic Infections
Ellen Wasan1, Tavonga Mandava1, Pablo Crespo-Moran1
1College of Pharmacy and Nutrition, University of Saskatchewan, Health Sciences Building, Saskatoon, SK S7N 5E5, Canada.
Abstract:
Amphotericin B (AmpB) is a polyene macrolide antibiotic used in the treatment of blood-borne parasitic and fungal infections. However, its use, particularly in the developing world, has been limited by dose-dependent kidney toxicity, other systemic-related toxicity issues following injection, the inconvenience of parenteral administration, and accessibility. Oral formulation approaches have focused on the dual problem of solubility and permeability of AmpB, which is poorly water soluble, amphoteric and has extremely low oral bioavailability. Therefore, to enhance oral absorption, researchers have employed micellar formulations, polymeric nanoparticles, cochleates, pro-drugs, and self-emulsifying drug delivery systems (SEDDS). This paper will highlight current uses of AmpB against parasitic infections such as leishmaniasis, preclinical and clinical formulation strategies, applications in veterinary medicine and the importance of developing a cost-effective and safe oral AmpB formulation.
Insights
Amphotericin B (AmpB) is vital for treating parasitic and fungal infections but faces toxicity and administration challenges. New oral formulations aim to improve its efficacy and accessibility, especially in developing nations.
Area of Science:
- Pharmacology
- Infectious Diseases
- Drug Delivery Systems
Background:
- Amphotericin B (AmpB) is a critical antifungal and antiparasitic macrolide antibiotic.
- AmpB use is restricted by severe kidney toxicity, systemic side effects, parenteral administration, and limited accessibility, particularly in developing countries.
- Poor water solubility and low oral bioavailability of AmpB present significant challenges for oral drug delivery.
Purpose of the Study:
- To review the current applications of Amphotericin B in treating parasitic infections like leishmaniasis.
- To explore preclinical and clinical strategies for developing improved oral formulations of AmpB.
- To emphasize the need for cost-effective and safe oral AmpB formulations for enhanced patient access and therapeutic outcomes.
Main Methods:
- Review of existing literature on Amphotericin B formulations and applications.
- Analysis of various drug delivery systems, including micellar formulations, nanoparticles, cochleates, pro-drugs, and SEDDS.
- Examination of preclinical and clinical data on oral AmpB formulation strategies.
Main Results:
- Various advanced drug delivery systems have been investigated to overcome AmpB's poor solubility and bioavailability.
- Promising preclinical and clinical results have been observed with novel oral formulations.
- Successful applications of AmpB in veterinary medicine highlight its broad therapeutic potential.
Conclusions:
- Developing safe and effective oral formulations of Amphotericin B is crucial for expanding its therapeutic use.
- Improved oral delivery systems can mitigate AmpB's toxicity and administration challenges, enhancing accessibility.
- Further research into cost-effective oral AmpB formulations is essential for global health initiatives, particularly for neglected tropical diseases.
