Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo

Rebecca Klippstein, Julie Tzu-Wen Wang, Riham I El-Gogary, Jie Bai, Falisa Mustafa, Noelia Rubio, Sukhvinder Bansal, Wafa T Al-Jamal, Khuloud T Al-Jamal

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Abstract

Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil-cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non-PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer.

Original languageEnglish
Pages (from-to)4704-22
JournalSmall
Volume11
Issue number36
DOIs
Publication statusPublished - 23 Sep 2015
Externally publishedYes

Keywords

  • Animals
  • Antineoplastic Agents
  • Apoptosis
  • Cell Line, Tumor
  • Colonic Neoplasms
  • Curcumin
  • Drug Carriers
  • Drug Delivery Systems
  • Female
  • Lactic Acid
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred BALB C
  • Multimodal Imaging
  • Nanocapsules
  • Nanomedicine
  • Nanoparticles
  • Neoplasm Transplantation
  • Particle Size
  • Polyethylene Glycols
  • Polyglycolic Acid
  • Polymers
  • Spectroscopy, Fourier Transform Infrared
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed
  • Journal Article
  • Research Support, Non-U.S. Gov't

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  • Cite this

    Klippstein, R., Wang, J. T-W., El-Gogary, R. I., Bai, J., Mustafa, F., Rubio, N., Bansal, S., Al-Jamal, W. T., & Al-Jamal, K. T. (2015). Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo. Small, 11(36), 4704-22. https://doi.org/10.1002/smll.201403799