Transethosomal gel for enhancing transdermal delivery of natural therapeutics

Abstract

Transethosomes, a fusion of transferosomes and ethosomes, combine the advantageous attributes of both vesicular systems to enhance deformability and skin permeation. While skin delivery is effective for drug transport, overcoming the skin barrier remains a significant challenge, particularly for plant-based products with poor permeability. Transethosomes offer a promising solution, but their low viscosity and retention on skin surfaces led to the development of transethosomal gels. These gels can entrap unstable and high molecular weight herbal extracts, fractions and bioactive compounds, facilitating enhanced drug delivery to the inner layers of the skin. This review focuses on the superior performance of transethosomes compared with conventional lipid-based nanovesicular systems, offering an advanced approach for transdermal delivery of plant-based drugs with improved permeability and stability.

GRAPHICAL ABSTRACT

Article highlights

• Transdermal drug delivery is valued for controlled release and avoiding first-pass metabolism.

• Traditional formulations face challenges due to the skin's barrier, especially the stratum corneum. Transethosomes (TEs) offer a solution by disrupting lipid bilayers and enhancing drug permeation.

• However, TEs' low viscosity and skin surface retention need improvement. Transethosomal gel formulations combine TEs with a gel matrix, addressing these issues. These gels offer enhanced drug retention and controlled release.

• They hold promise for various therapeutic applications, but optimization is crucial for efficacy and safety.

Properties of transethosomes

• Transethosomes are a combination of transferosomes and ethosomes. Which is composed of phospholipids, edge activators and ethanol.

• The flexibility of TEs facilitates penetration through skin lipid bilayers. Allow for the entrapment of high molecular weight, both hydrophilic and lipophilic phytochemical drugs, showing versatility.

Mechanism of action of transethosomes

• Transethosomes penetrate deeper skin layers through two mechanisms: the ethanol impact mechanism and the vesicular mechanism, which involves hydrotaxis and elastomechanics. The ethanol impact mechanism relies on the solvent's ability to disrupt the skin's lipid barrier, facilitating penetration. Meanwhile, the vesicular mechanism utilizes the deformability and elasticity of transethosomes to navigate through the skin's layers, aided by hydration gradients and mechanical forces.

Advantages of TEs & TEs gel in drug delivery

• TEs and TEs gel offers several advantages, including high patient compliance, avoidance of first-pass metabolism, improved bioavailability, high entrapment efficiency and controlled release.

• These properties make TEs and TEs gel promising candidates for effective transdermal drug delivery.

Preparation methods of transethosomes

• Transethosomes are prepared following different preparation techniques: Solvent Injection Method, Thin-Film Hydration Method, Ethanol Injection Method, Reverse Phase Evaporation Method, Freeze-Thaw Method.

Characterization & evaluation of TEs & TEs gel

• Techniques like particle size analysis, TEM, zeta potential measurement and FTIR spectroscopy provide insights into size, structure, stability and composition, ensuring their quality and effectiveness.

• The evaluation of transethosomal gel involves assessing its physical properties, drug release kinetics, skin permeation and stability. Techniques such as viscosity measurement, spreadability testing, drug release studies, skin permeation assays and stability testing under various conditions are employed to ensure their suitability for transdermal drug delivery.

Optimization of TEs & TEs gel formulations

• To maximize the potential of TEs and TEs gel, several factors need careful consideration, including stability, purity of phospholipids, loading capacity, entrapment efficiency and formulation methodology.

• Optimization of these parameters is crucial for ensuring the efficacy and safety of TEs and TEs gel in transdermal drug delivery.

Therapeutic applications of TEs gel

• Various TEs gel formulations, entrapping different plant extracts and bioactive compounds, have demonstrated high lipid solubility and therapeutic efficacy.

• Applications include pain management, dermatology, treatment of skin cancers, antibacterial therapy and systemic drug delivery.

Keywords: :

• deformable vesicles
• nanocarriers
• natural therapeutics
• plant bioactives
• skin permeation
• TDDS
• transethosomal gel
• transethosomes
• ultra-flexible

Acknowledgments

The authors are extremely grateful to the Department of Pharmaceutical Engineering & Technology, IIT (BHU), Varanasi for providing infrastructural facilities.

The authors gratefully acknowledge the Indian Institute of Technology (Banaras Hindu University), Varanasi, India, for providing infrastructural facilities. The authors are also immensely grateful for the scholarship granted by the Ministry of Education, Government of India, providing financial support for this work.

Author contributions

S D Malang and Shambhavi contributed to the conceptualization and writing of the original manuscript. A N Sahu contributed to conceptualization, supervision, expert assistance, editing, drafting and revision functions.

Financial disclosure

The authors have no 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.

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.