Bromelain-Functionalized Multiple-Wall Lipid-Core Nanocapsules: Formulation, Chemical Structure and Antiproliferative Effect Against Human Breast Cancer Cells (MCF-7)

Pharm Res. 2017 Feb;34(2):438-452. doi: 10.1007/s11095-016-2074-2. Epub 2016 Dec 15.

Abstract

Purpose: This study was conducted a promising approach to surface functionalization developed for lipid-core nanocapsules and the merit to pursue new strategies to treat solid tumors.

Methods: Bromelain-functionalized multiple-wall lipid-core nanocapsules (Bro-MLNC-Zn) were produced by self-assembling following three steps of interfacial reactions. Physicochemical and structural characteristics, in vitro proteolytic activity (casein substrate) and antiproliferative activity (breast cancer cells, MCF-7) were determined.

Results: Bro-MLNC-Zn had z-average diameter of 135 nm and zeta potential of +23 mV. The complex is formed by a Zn-N chemical bond and a chelate with hydroxyl and carboxyl groups. Bromelain complexed at the nanocapsule surface maintained its proteolytic activity and showed anti-proliferative effect against human breast cancer cells (MCF-7) (72.6 ± 1.2% at 1.250 μg mL-1 and 65.5 ± 5.5% at 0.625 μg mL-1). Comparing Bro-MLNC-Zn and bromelain solution, the former needed a dose 160-folds lower than the latter for a similar effect. Tripan blue dye assay corroborated the results.

Conclusions: The surface functionalization approach produced an innovative formulation having a much higher anti-proliferative effect than the bromelain solution, even though both in vitro proteolytic activity were similar, opening up a great opportunity for further studies in nanomedicine.

Keywords: MCF-7 human breast cancer cells; bromelain; lipid-core nanocapsules; metal-chitosan complex; surface-functionalized nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Bromelains / chemistry*
  • Bromelains / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Chemistry, Pharmaceutical / methods
  • Drug Carriers / chemistry
  • Female
  • Humans
  • Lipids / chemistry*
  • MCF-7 Cells
  • Nanocapsules / chemistry*
  • Nanomedicine / methods
  • Particle Size

Substances

  • Drug Carriers
  • Lipids
  • Nanocapsules
  • Bromelains