Fungal Infection Treatment

Fungal diseases are usually confined to superficial infections and currently affect nearly a quarter of the global population. Resistance of pathogenic fungi is growing with the use of antifungal drugs. With the rapid development of modern medicine, there is an increasing interest in new compounds with potential new mechanisms and application possibilities. As a special type of polymer, dendrimers have a tightly defined structure and many functionalization possibilities, which allow them to be used as effective antifungal drug carriers in addition to their own antifungal activity.

The Control and Therapy of Fungal Infections

Fungi can be divided into two categories: ongoing pathogens and opportunistic fungi. Fungal diseases affect approximately billions of people each year and include common superficial fungal infections and severe systemic infections depending on the pathogen and the patient's immune status. Opportunistic fungi, such as Candida, Aspergillus and Cryptococcus and Trichophyton, cause infections when the host's natural defense mechanisms are compromised. These invasive systemic opportunistic fungal diseases are an important cause of morbidity and mortality in critically ill patients. Research on antifungal drugs dates to the 1950s, when ashwagandha was considered to have selective inhibitory activity against fungi. Later, other drugs were gradually introduced into clinical practice. The number of drugs currently used to treat fungal infections is very limited, and those that are clinically necessary and used in therapy include polyenes, azoles and triazoles, antimetabolites, allylamines, polyketides, echinocandins, morpholines, undecylenic acid and ciclopirox. There are three general mechanisms of action of antifungal drugs.

Despite the availability of several classes of antifungal drugs, treatment of fungal infections remains difficult due to their narrow range of activity, restricted routes of administration, and adverse interactions. In addition, the difficulties in treating fungal infections include increasing drug resistance. Therefore, there is a need for more effective, safer, and cost-effective antifungal drugs as well as new therapeutic options that can counter resistance and increase the spectrum of antifungal drug activity.

Dendrimers for the Treatment of Fungal Infections

Potential alternatives to drugs can be obtained from different sources, such as natural products, nanomaterials, or chemically synthesized substances. Nanoparticles and biomaterials play an increasingly important role in modern drug formulations and biomedical research, and many polymers have antifungal activity. Noteworthy are dendrimers, which, as highly branched polymers, have been designed as potential antimicrobial agents due to the possibility of peripheral group modifications.

• Dendrimers antifungal activity per se
  Polymers with intrinsic antimicrobial activity possess cationic groups that interact with negatively charged microbial membranes. The antifungal activity of the dendrimer itself is exerted by the following mechanisms.

• Electrostatic interaction of cationic groups of dendrimers with anion-bearing cell membranes, causing membrane fluctuations and increased permeability
• Disruption of cell membranes and formation of small pores to prevent membrane reconstruction through a carpet mechanism
• inhibition of 1,3-β-D-glucan synthase, leading to impairment of cell wall synthesis and leakage of cellular components
• Blocking microbial enzymes using chelation mechanism

Dendrimers modified with ferrocene moieties in the periphery can be used in antifungal formulations. (Mlynarczyk DT, et al., 2021)

• Dendrimers as antifungal drug delivery carriers
  In addition to their antifungal activity, dendrimers are also used as potential carriers of antifungal drugs due to their drug encapsulation ability. On the one hand, many end groups of dendrimers can interact with certain molecules through electrostatic interactions. On the other hand, covalent bonds can be formed between the end groups of dendrimers and active drugs.

How We Can Help

At CD BioSciences, we have the expertise and advanced technology platform dedicated to providing high quality dendrimer products and customized services to our global customers. If you are interested in our services or have any additional questions, please feel free to contact us.

Reference

1. Mlynarczyk DT.; et al. Dendrimers against fungi - A state of the art review. Control Release. 2021, 330: 599-617.