Pharmaceutical Research

, Volume 34, Issue 2, pp 438–452 | Cite as

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

  • Catiúscia P. Oliveira
  • Willian A. Prado
  • Vladimir Lavayen
  • Sabrina L. Büttenbender
  • Aline Beckenkamp
  • Bruna S. Martins
  • Diogo S. Lüdtke
  • Leandra F. Campo
  • Fabiano S. Rodembusch
  • Andréia Buffon
  • Adalberto PessoaJr
  • Silvia S. Guterres
  • Adriana R. Pohlmann
Research Paper



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.


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.


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.


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.


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





One-way analysis of variance


Acridine orange base


Bromelain-functionalized multiple-wall lipid-core nanocapsules


Caprylic/capric triglyceride


Center of Nanoscience and Nanotechnology at the Federal University of Rio Grande do Sul


AO-labeled chitosan


Median diameter


Particle diameter at percentile 90 under the particle size distribution curves




Dulbecco’s modified Eagle’s medium




Dimethyl sulfoxide


N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride


Fetal bovine serum


Human epidermal growth factor receptor


Lipid-core nanocapsule


Cationic lipid-core nanocapsules/lecithin-chitosan-polysorbate 80-coated lipid-core nanocapsules


Lecithin-polysorbate 80-coated lipid-core nanocapsules

log D

Distribution coefficient


Multi-wall lipid-core nanocapsules


Mammalian target of rapamycin


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


Nanoparticle tracking analysis




Rhodamine B-poly(ε-caprolactone) conjugate


Polydispersity index




Phenylalanine-functionalized multi-wall lipid-core nanocapsules


Particle number density


Rhodamine B


Surface area


Trichloroacetic acid


Transmission electron microscopy



Catiúscia Padilha de Oliveira and Willian Andrade de Prado thanks the Brazilian Agency CAPES for their fellowships. The authors thank the Grants from Brazilian Agencies: CNPq/Brasilia/Brazil, CAPES/MEC and FAPERGS. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Catiúscia P. Oliveira and Willian A. Prado contributed equally. The authors report no conflicts of interest in this work.

Supplementary material

11095_2016_2074_MOESM1_ESM.docx (3.1 mb)
ESM 1 (DOCX 3197 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Catiúscia P. Oliveira
    • 1
    • 2
  • Willian A. Prado
    • 3
  • Vladimir Lavayen
    • 3
  • Sabrina L. Büttenbender
    • 3
  • Aline Beckenkamp
    • 1
  • Bruna S. Martins
    • 3
  • Diogo S. Lüdtke
    • 3
  • Leandra F. Campo
    • 3
  • Fabiano S. Rodembusch
    • 3
  • Andréia Buffon
    • 1
  • Adalberto PessoaJr
    • 4
  • Silvia S. Guterres
    • 1
  • Adriana R. Pohlmann
    • 1
    • 2
    • 3
  1. 1.Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de FarmáciaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Departamento de Química Orgânica, Instituto de QuímicaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em Química, Instituto de QuímicaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Faculdade de Ciências FarmacêuticasUniversidade de São PauloSão PauloBrazil

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