Development and optimisation of 3-Acetyl-11-keto-β-boswellic acid loaded poly-lactic-co-glycolic acid-nanoparticles with enhanced oral bioavailability and in-vivo anti-inflammatory activity in rats

J Pharm Pharmacol. 2015 Sep;67(9):1188-97. doi: 10.1111/jphp.12420. Epub 2015 Apr 7.

Abstract

Objectives: 3-Acetyl-11-keto-β-boswellic acid (AKBA) is a potent anti-inflammatory compound of Boswellia serrata. However, anti-inflammatory activity of AKBA is impeded by poor oral bioavailability due to its poor aqueous solubility. In this context, we aimed to develop poly lactic-co-glycolic acid (PLGA)-based nanoparticle formulation of AKBA (AKBA-NPs) in order to improve its oral bioavailability and in-vivo anti-inflammatory activity in rats.

Methods: AKBA-NPs were prepared and characterised by analysing particle size and zeta potential using zeta sizer, surface morphology by scanning electron microscopy and transmission electron microscopy, and physical property using differential scanning calorimetry and X-ray diffraction techniques. The optimised nanoparticles were evaluated for in-vitro drug release and oral bioavailability studies, and in-vivo anti-inflammatory activity by carrageenan-induced rat paw oedema method.

Key findings: The optimised AKBA-NPs showed the particle size of 179.6 nm with 0.276 polydispersity index and entrapment efficiency of 82.5%. AKBA-NPs showed increased in-vivo anti-inflammatory activity as compared with AKBA. Bioavailability study revealed about six times higher peak plasma concentration of AKBA in AKBA-NPs. Moreover, t1/2 and total area under the curve of AKBA were also enhanced by two and ninefold, respectively, in AKBA-NPs as compared with corresponding AKBA.

Conclusions: The promising results of improved oral bioavailability and in-vivo anti-inflammatory activity of AKBA suggested the successful nanoparticle formulation of AKBA.

Keywords: AKBA; Boswellia serrata; anti-inflammatory activity; nanoparticles; oral bioavailability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacokinetics*
  • Anti-Inflammatory Agents / pharmacology
  • Biological Availability
  • Boswellia / drug effects
  • Chemistry, Pharmaceutical / methods
  • Female
  • Lactic Acid / chemistry*
  • Male
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Triterpenes / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Triterpenes
  • acetyl-11-ketoboswellic acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid