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

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 d...

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Published in:Small (Weinheim an der Bergstrasse, Germany) Vol. 11; no. 36; pp. 4704 - 4722
Main Authors: Klippstein, Rebecca, Wang, Julie Tzu-Wen, El-Gogary, Riham I., Bai, Jie, Mustafa, Falisa, Rubio, Noelia, Bansal, Sukhvinder, Al-Jamal, Wafa T., Al-Jamal, Khuloud T.
Format: Journal Article
Language:English
Published: Germany Blackwell Publishing Ltd 01-09-2015
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Summary: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. An oil‐cored nanocapsule (NC) containing a high dose of curcumin is prepared. The NC delivers curcumin to colon cancer (CT26) in vitro, and reaches solid tumor after intravenous injection in mouse models, as shown by optical imaging and single photon emission computed tomography/computed tomography (SPECT/CT). The presence of the drug in the tumor is confirmed by high‐performance liquid chromatography. Apoptosis of proliferating cells is confirmed by TUNEL staining.
Bibliography:Biotechnology and Biological Sciences Research Council - No. BB/J008656/1
King's-China Scholarship Council
EU FP7-ITN Marie-Curie Network programme RADDEL - No. 290023
ArticleID:SMLL201403799
Worldwide Cancer Research - No. 12-1054
istex:8CA635803EB89C5837478F7AD46CC62F74E102F5
ark:/67375/WNG-QMPGVRGF-P
Prostate Cancer UK - No. CDF-12-002
The copyright line for this article was changed on 4 Nov 2015 after original online publication.
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ISSN:1613-6810
1613-6829
DOI:10.1002/smll.201403799