Berberine-Loaded Nanostructured Lipid Carriers Enhance the Treatment of Ulcerative Colitis

Int J Nanomedicine. 2020 Jun 3:15:3937-3951. doi: 10.2147/IJN.S247406. eCollection 2020.

Abstract

Purpose: Berberine (BBR), a major ingredient extracted from Coptis chinensis, is a natural drug with limited oral bioavailability. We developed nanostructured lipid carriers (NLCs) as a delivery system for enhanced anti-inflammatory activity of BBR against ulcerative colitis (UC).

Methods: BBR-loaded nanostructured lipid carriers (BBR-NLCs) prepared via high-pressure homogenization were evaluated for particle size, zeta potential, drug entrapment efficiency, drug loading, drug release, toxicity, and cellular uptake. The anti-UC activities of free and encapsulated BBR were evaluated in a DSS-induced acute model of UC in mice.

Results: Spherical BBR-NLCs were prepared with a particle size of 63.96± 0.31 nm, a zeta potential of +3.16 ± 0.05 mV, an entrapment efficiency of 101.97±6.34%, and a drug loading of 6.00±0.09%. BBR-NLCs showed excellent biocompatibility in vivo. Cellular uptake experiments showed that BBR-NLCs improved uptake of BBR by RAW 264.7 cells and Caco-2 cells. Oral administration of BBR-NLCs significantly alleviated colitis symptoms (DAI, colon length, spleen swelling, MPO activity) through inhibition of NF-κB nuclear translocation, decreased expression of pro-inflammatory cytokines (IL-1β, IL-6, MMP-9, CX3CR1, COX-2, TERT), and increased expression of the tight junction protein ZO-1.

Conclusion: BBR-loaded NLCs improved colitis symptoms, which suggested that this may be a novel formulation for treatment of UC.

Keywords: anti-inflammatory; berberine; nanostructured lipid carriers; ulcerative colitis.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Berberine / administration & dosage*
  • Berberine / pharmacokinetics
  • Berberine / pharmacology
  • Caco-2 Cells
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Humans
  • Lipids / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry*
  • Particle Size
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drug Carriers
  • Lipids
  • Berberine
  • Dextran Sulfate