Preparation of protamine-hyaluronic acid coated core-shell nanoparticles for enhanced solubility, permeability, and oral bioavailability of decoquinate

Wei Wei; Min Lu; Wenhao Xu; Nikolay E Polyakov; Alexandr V Dushkin; Wei-Ke Su

doi:10.1016/j.ijbiomac.2022.07.152

Preparation of protamine-hyaluronic acid coated core-shell nanoparticles for enhanced solubility, permeability, and oral bioavailability of decoquinate

Int J Biol Macromol. 2022 Oct 1:218:346-355. doi: 10.1016/j.ijbiomac.2022.07.152. Epub 2022 Jul 22.

Authors

Wei Wei¹, Min Lu¹, Wenhao Xu¹, Nikolay E Polyakov², Alexandr V Dushkin³, Wei-Ke Su⁴

Affiliations

¹ National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, PR China.
² Institute of Chemical Kinetics and Combustion, Novosibirsk 630090, Russia; Institute of Solid State Chemistry and Mechanochemistry, Novosibirsk, Russia.
³ National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, PR China; Institute of Solid State Chemistry and Mechanochemistry, Novosibirsk, Russia. Electronic address: drivergood@mail.ru.
⁴ National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, PR China; Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, PR China. Electronic address: pharmlab@zjut.edu.cn.

PMID: 35878671
DOI: 10.1016/j.ijbiomac.2022.07.152

Abstract

Decoquinate (DQ) has low oral bioavailability owing to its poor water solubility. In this study, a DQ solid dispersion (DQ-SD) was fabricated using mechanochemical technology to encapsulate DQ and improve its oral bioavailability. DQ-SD is easily generated via self-assembly in the aqueous phase to form micelles consisting of disodium glycyrrhizinate (Na₂GA) nanoparticles with a protamine (PRM) and anionic hyaluronic acid (HA) layers. The spherical DQ nanoparticles with an average diameter of 114.95 nm were obtained in an aqueous phase with a critical micelle concentration of 0.157 mg/mL, zeta potential of -38.38 mV, polydispersity index of 0.200, and drug loading of 5.66 %. The dissolution rate and cumulative release of DQ-SD were higher than those of pure DQ. Furthermore, the bioavailability of DQ-SD was approximately 6.3 times higher than that of pure DQ. Pharmacokinetic and biodistribution studies indicated that DQ-SD possessed a significantly higher concentration in the blood and preferential liver tissue accumulation, than that of pure DQ. The developed DQ-SD exhibited considerable potential for developing old DQ for a new application as a hematogenous parasite drug and provides a reference for developing more efficient delivery systems for hydrophobic bioactive agents.

Keywords: Bioavailability; Decoquinate; Mechanochemistry; Micelle; Solubility.

MeSH terms

Administration, Oral
Biological Availability
Decoquinate*
Hyaluronic Acid
Micelles
Nanoparticles* / chemistry
Particle Size
Permeability
Protamines
Solubility
Tissue Distribution

Substances

Micelles
Protamines
Decoquinate
Hyaluronic Acid