Conjugates of amphotericin B to resolve challenges associated with its delivery

ABSTRACT

Introduction

Amphotericin B (AmB), a promising antifungal and antileishmanial drug, acts on the membrane of microorganisms. The clinical use of AmB is limited due to issues associated with its delivery including poor solubility and bioavailability, instability in acidic media, poor intestinal permeability, dose and aggregation state dependent toxicity, parenteral administration, and requirement of cold chain for transport and storage, etc.

Areas covered

Scientists have formulated and explored various covalent conjugates of AmB to reduce its toxicity with increase in solubility, oral bioavailability, and payload or loading of AmB by using various polymers, lipids, carbon-based nanocarriers, metallic nanoparticles, and vesicular carriers, etc. In this article, we have reviewed various conjugates of AmB with polymers and nanomaterials explored for its delivery to give a deep insight regarding further exploration in future.

Expert opinion

Covalent conjugates of AmB have been investigated by scientists, and preliminary in vitro and animal investigations have given successful results, which are required to be validated further with systematic investigation on safety and therapeutic efficacy in animals followed by clinical trials.

KEYWORDS:

• Bioavailability
• drug delivery
• polymer-drug conjugates
• solubility
• toxicity
• aggregation

Article highlights

• Delivery of Amphotericin B (AmB) has been a major challenge for many decades despite its efficient therapeutic efficacy against fungal and leishmanial infection.

• Its relatively safe liposomal formulation, AmBisome®, shows variable therapeutic efficacy according to region and immunity of patients, and required to be given parenterally.

• AmB is one of the most explored drugs for delivery strategies, but no strategy has translated clinically, which implies requirement of a comprehensive investigation and data on safety and efficacy.

• Conjugates of AmB formulated with polymers and nanomaterials have shown improvement in water solubility, bioavailability, stability, reduction in toxicity with high encapsulation efficiency without compromising the efficacy of AmB.

• Among all conjugates, arabinogalactan-AmB conjugates have been investigated most.

• AmB conjugated with nanocarriers have been observed to show different pattern of aggregation from pure AmB in much research.

• AmB conjugated delivery system could resolve various challenges associated with its delivery by improving its solubility due to hydrophilic groups present in polymers or by providing synergistic antifungal activity or by increasing selectivity toward macrophages or by providing theranostic application due to attached imaging agent or by increasing bioavailability and therapeutic activity due to nanometric size.

This box summarizes key points of this article.

Declaration of interest

K Jain is thankful to Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India for providing the support to write this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

NIPER Raebareli communication number of this manuscript is NIPER-R/communication/496.

References

Additional information

Funding

Author VK Jain is grateful to Indian Council of Medical Research (ICMR), New Delhi for providing financial support in the form of ICMR – Senior Research Fellowship (ICMR-SRF) [Ref. No.45/65/2020-Nan/BMS; Proposal ID: 2020-8843].