Treatment of spinal tuberculosis in rabbits using bovine serum albumin nanoparticles loaded with isoniazid and rifampicin

Neurol Res. 2022 Mar;44(3):268-274. doi: 10.1080/01616412.2021.1979749. Epub 2021 Sep 28.

Abstract

Objective: To evaluate the clinical efficacy of bovine serum albumin nanoparticles loaded with isoniazid and rifampicin (INH-RFP-BSA-NPs) in the treatment of spinal tuberculosis in rabbits.

Methods: 35 spinal tuberculosis rabbit models were grouped into three groups, including 14 in group A and group B respectively and 7 in group C.All rabbits in group A were treated by INH-RFP-BSA-NPs's injection and in group B were treated with classic dosage form of INH and RFP, while in group C normal saline was given as the blank control. After intervention, the body weighing and CT scan, as well as concentration's measurement of INH and RFP in blood and tissues, were performed in all rabbits at the time of the 6thweek and 12th week, respectively.

Results: In group A, rabbits' weight increased by 0.44 kg and 0.27 kg within 6 weeks and 12 weeks' treatment respectively. The bactericidal concentrations of 1.64 µg•g-1 for INH and 21.36 µg•g-1 for RFP were measured in focus vertebral body 6 weeks post-injection and six weeks later the concentrations of INH and RFP in vertebral body still maintained at the level of 1.96 µg•g-1 and 22.35 µg•g-1respectively. After 12 weeks therapy, CT-scanned showed all the necrotic tissue was replaced by normal bone tissue. In group B, all rabbits had no significant increment of body weight and 4 rabbits had paralysis of hind leg. The concentrations of INH and RFP in vertebral body and focus were much lower than group A. CT-scanned showed the focus vertebral body was only partially repaired after 12 weeks' therapy.

Conclusion: The INH-RFP-BSA-NPs has the characteristics of sustained release in vivo and target biodistribution in focus vertebral body. Its therapeutic effect in rabbit spinal tuberculosis is much better than common INH and RFP.

Keywords: Spinal tuberculosis; bovine serum albumin; isoniazid; nanoparticles; rifampin.

MeSH terms

  • Animals
  • Antibiotics, Antitubercular / administration & dosage
  • Antibiotics, Antitubercular / pharmacology*
  • Delayed-Action Preparations
  • Disease Models, Animal
  • Isoniazid / administration & dosage
  • Isoniazid / pharmacokinetics
  • Isoniazid / pharmacology*
  • Nanoparticles* / administration & dosage
  • Rabbits
  • Rifampin / administration & dosage
  • Rifampin / pharmacokinetics
  • Rifampin / pharmacology*
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / pharmacokinetics
  • Serum Albumin, Bovine / pharmacology*
  • Tuberculosis, Spinal / drug therapy*

Substances

  • Antibiotics, Antitubercular
  • Delayed-Action Preparations
  • Serum Albumin, Bovine
  • Isoniazid
  • Rifampin