Human serum albumin nanoparticles as nanovector carriers for proteins: Application to the antibacterial proteins "neutrophil elastase" and "secretory leukocyte protease inhibitor"

Int J Pharm. 2020 Apr 15:579:119150. doi: 10.1016/j.ijpharm.2020.119150. Epub 2020 Feb 15.

Abstract

The use of proteins and defined amino acid sequences as therapeutic drugs have gained a certain interest in the past decade. However, protein encapsulation within protein nanoparticles was never endeavored. For this reason, human serum albumin (HSA) nanoparticles were prepared by nanoprecipitation method. The process was optimized, and particles were obtained with a size of 120 nm and zeta potential of -25 mV. Neutrophil elastase (NE) and secretory leukocyte protease inhibitor (SLPI) were encapsulated separately within HSA nanoparticles. Gel electrophoresis and western blot studies demonstrate the successful encapsulation and the stability of the particles. On the other hand, enzymatic assays show that encapsulated NE lost its proteolytic activity, whereas encapsulated SLPI maintained its inhibitory property. In addition, the antibacterial studies showed that both formulations were able to drastically reduce bacterial growth of Pseudomonas aeruginosa. This work showed the possibility of using both NE and SLPI as anti-bacterial agents through encapsulation within HSA nanoparticles.

Keywords: Antibacterial; Elastase; Enzyme encapsulation; Protein nanoparticles; SLPI.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Drug Carriers / chemistry*
  • Drug Compounding / methods
  • Drug Stability
  • Enzyme Assays
  • Humans
  • Leukocyte Elastase / administration & dosage
  • Leukocyte Elastase / chemistry
  • Microbial Sensitivity Tests
  • Nanoparticles / chemistry
  • Protein Stability
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / growth & development
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Secretory Leukocyte Peptidase Inhibitor / administration & dosage
  • Secretory Leukocyte Peptidase Inhibitor / chemistry
  • Serum Albumin, Human / chemistry*

Substances

  • Anti-Bacterial Agents
  • Drug Carriers
  • Recombinant Proteins
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • ELANE protein, human
  • Leukocyte Elastase
  • Serum Albumin, Human