Ethosomal Gel for Improving Transdermal Delivery of Thymosin β-4

Abstract

Purpose

Thymosin β-4(Tβ-4) is a macromolecular protein drug with potential for drug development in wound repair but is limited by the shortcomings of macromolecular protein, such as large volumes, poor membrane permeability, and unstable physicochemical characteristics. Ethosomes could enhance cell membrane fluidity and reduce epidermal membrane density to make macromolecular drugs through the stratum corneum into the deeper layers of the skin easily. Herein, we developed and characterized a novel transdermal delivery vehicle to load macromolecular protein peptides and use Tβ-4 as a model drug wrapped into ethosomes.

Methods

We used the orthogonal method to optimize the formulation of the ethosome preparation prepared by the ethonal infusion method. Ethosomal gels were characterized by using different analytical methods. Transdermal release rate in vitro have been demonstrated in Franz diffusion cells and the efficacy of drug-loaded nanocarriers in vivo was investigated in a mouse model.

Results

Optimized Tβ-4 ethosomal gels have good physicochemical properties. The drug amounts of the cumulative release in the ethosomal gel within 5 hours were 1.67 times that of the T-β4 gel in vitro release study, and the wound healing time of ethosomal gel group was only half of the T-β4 gel group in vivo pharmacokinetic study. Compared with the free drug group, the ethosome preparation not only promotes the percutaneous absorption process of the macromolecular protein drugs but also shortened wound recovery time.

Conclusion

Hence, we provide a possible good design for ethosomal gel system that can load macromolecular protein peptide drugs to achieve transdermal drug administration, promoting the percutaneous absorption of the drug and improving the effect.

Keywords:

• ethosomes
• transdermal drug delivery system
• macromolecular protein drugs
• skin wound healing

Acknowledgments

This work was supported by the Fundamental Research Funds of Shandong University (No. 2018JC006), the National Natural Science Foundation of China (No. 21873057), Shandong Provincial Natural Science Foundation of China (No. ZR2019MB041), and the Major Basic Research Project of Shandong Natural Science Foundation, P.R. China (No. ZR2018ZC0232).

Ethics Approval and Informed Consent

School of Pharmaceutical Science, Shandong University ethics committee has approved the animal model experiments.

Disclosure

The authors report no conflicts of interest in this work.