Secondary metabolites in topical infectious diseases and nanomedicine applications

Abstract

Topical infection affects nearly one-third of the world's population; it may result from poor sanitation, hygienic conditions and crowded living and working conditions that accelerate the spread of topical infectious diseases. The problems associated with the anti-infective agents are drug resistance and long-term therapy. Secondary metabolites are obtained from plants, microorganisms and animals, but they are metabolized inside the human body. The integration of nanotechnology into secondary metabolites is gaining attention due to their interaction at the subatomic and skin-tissue levels. Hydrogel, liposomes, lipidic nanoparticles, polymeric nanoparticles and metallic nanoparticles are the most suitable carriers for secondary metabolite delivery. Therefore, the present review article extensively discusses the topical applications of nanomedicines for the effective delivery of secondary metabolites.

Executive summary

Plant secondary metabolites

• Plants possess several secondary metabolites demonstrating antimicrobial properties, including flavonoids, alkaloids, tannins and terpenoids.

Animal secondary metabolites

• Only a handful of secondary metabolites that have antimicrobial properties have been identified from animal sources.

• To date, no nanoformulation has been developed from animal secondary metabolites to treat topical infections.

• This field requires more scientific investigation to gain a better understanding of animal secondary metabolites and their delivery for topical applications.

Microorganism secondary metabolites

• Some researchers have reported that microbial pigments (e.g., melanin, carotenoids, violacein, quinones, flavonoids and manascins), which are the secondary metabolites of microorganisms, show good antimicrobial properties.

Skin barrier function

• The skin has a complex structure and diverse biophysical properties that modulate its barrier function.

• Specifically, the stratum corneum layer creates a barrier that facilitates the permeation of hydrophobic molecules more efficiently than hydrophilic molecules. However, the hydrophilic bilayer region hinders highly hydrophobic compounds.

Environmental & individual factors

• Drug delivery through the skin is heavily influenced by environmental factors (temperature, oxygen level, humidity and light) and individual factors (sex, age, skin anatomy, hormonal balance and humidity).

Drug stability & compatibility

• Developing strategies to enter the skin and efficiently deliver therapeutics is a significant area of research.

• Drugs quickly and directly go through the skin through the intracellular route.

• This method is difficult, however, because the particle must get past the water- and fat-absorbing parts of skin cells.

• Moreover, the drug must be stable and compatible with the skin and the delivery system.

Nanocarriers

• Different kinds of nanocarriers, such as liposomes, microemulsions, hydrogels, solid lipids and polymeric nanoparticles, are used to deliver secondary metabolites such as curcumin, quercetin, berberine and eugenol into the skin.

• It has several advantages: controlled release, site-specific delivery, enhanced bioavailability, reduced toxicity, and increased solubility and stability.

Nanocarrier barrier

• Several barriers impede the seamless integration of this technology into practical applications.

• Nanoparticle synthesis and formulation are difficult because one must design and optimize these carriers carefully to encapsulate and protect secondary metabolites while also ensuring controlled release.

Nanotoxicity

• The toxicity of nanocarriers is influenced by composition, size, shape, surface charge, stability and biodegradability.

Keywords: :

• bacteria
• fungi
• nanomedicine
• nanotoxicology
• secondary metabolites
• skin
• topical infection
• virus

Author contributions

A Sahoo: drafting or revising the work critically for important intellectual content; substantial contributions to the conception or design of the work; or the acquisition, analysis and interpretation of data for the work. K Dwivedi: substantial contributions to the conception or design of the work; acquisition, analysis or interpretation of data for the work; drafting or revising the work critically for important intellectual content. WH Almalki: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting and revising the work critically for important intellectual content. AK Mandal: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting or revising the work critically for important intellectual content. A Alhamyani: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting or revising the work critically for important intellectual content. O Afzal: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting or revising the work critically for important intellectual content. ASA Altamimi: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting or revising the work critically for important intellectual content. NK Alruwaili: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work. PK Yadav: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; Md Abul Barkat: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work. T Singh: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work. M Rahman: agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafting or revising the work critically for important intellectual content. All authors were involved in reviewing and agreeing to all versions of the submission during revisions and final version.

Financial disclosure

The authors extend their appreciation to the Deanship for Research & Innovation, Ministry of Education, Saudi Arabia for funding this research work through project number IFP22UQU4310387DSR158. 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.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors extend their appreciation to the Deanship for Research & Innovation, Ministry of Education, Saudi Arabia for funding this research work through project number IFP22UQU4310387DSR158. 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.