Biodynamer Nano-Complexes and -Emulsions for Peptide and Protein Drug Delivery

Abstract

Background

Therapeutic proteins and peptides offer great advantages compared to traditional synthetic molecular drugs. However, stable protein loading and precise control of protein release pose significant challenges due to the extensive range of physicochemical properties inherent to proteins. The development of a comprehensive protein delivery strategy becomes imperative accounting for the diverse nature of therapeutic proteins.

Methods

Biodynamers are amphiphilic proteoid dynamic polymers consisting of amino acid derivatives connected through pH-responsive dynamic covalent chemistry. Taking advantage of the amphiphilic nature of the biodynamers, PNCs and DEs were possible to be prepared and investigated to compare the delivery efficiency in drug loading, stability, and cell uptake.

Results

As a result, the optimized PNCs showed 3-fold encapsulation (<90%) and 5-fold loading capacity (30%) compared to DE-NPs. PNCs enhanced the delivery efficiency into the cells but aggregated easily on the cell membrane due to the limited stability. Although DE-NPs were limited in loading capacity compared to PNCs, they exhibit superior adaptability in stability and capacity for delivering a wider range of proteins compared to PNCs.

Conclusion

Our study highlights the potential of formulating both PNCs and DE-NPs using the same biodynamers, providing a comparative view on protein delivery efficacy using formulation methods.

Graphical Abstract

Keywords:

• amphiphilic polymer
• nanocomplex
• double emulsion
• pH-responsive
• protein delivery
• dynamic covalent chemistry

Acknowledgments

Yun Liu is supported by a Ph.D. fellowship from the Chinese Scholarship Council. We also acknowledge technical support from Pascal Paul, Petra König, and Tabea Trampert at the Helmholtz Institute of Pharmaceutical Research Saarland (HIPS).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

WO2021259783A1 (EP3928798A1) was filed in relation to the article. The authors report no other conflicts of interest in this work.