Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
April-2015 Volume 46 Issue 4

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2015 Volume 46 Issue 4

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention

  • Authors:
    • Arvind Thakkar
    • Sushma Chenreddy
    • Jeffrey Wang
    • Sunil Prabhu
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA
  • Pages: 1827-1834
    |
    Published online on: February 5, 2015
       https://doi.org/10.3892/ijo.2015.2879
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The objective of the present study was to establish the individual and combined chemopreventive potential of a widely used non-steroidal anti-inflammatory drug, ibuprofen (IBU), encapsulated in solid lipid nanoparticles (SLNs) for the chemoprevention of pancreatic cancer. The IBU SLNs were optimized using various lipids (Stearic acid, Compritol 888 ATO and Tripalmitin) and surfactants (Poloxamer 188, Tween-80). The synergistic effect of combination of IBU with sulforaphane (SFN) was also evaluated. Cell viability studies were conducted followed by colony formation and NF-κB DNA binding assays. The IC50 concentration of free IBU in human pancreatic cancer Panc-1 and MIA PaCa-2 cells were 1.25 and 1.26 mM, respectively. SLN optimization study of IBU revealed stearic acid (1:2 drug to lipid ratio) formulated with Poloxamer 188 to be the most efficacious in cell viability study. Upon encapsulation in SLNs, IC50 concentration of IBU-SLN was 113.8 and 122.6 µM for Panc-1 and MIA PACa-2 cells, respectively, reflecting a 10-fold reduction compared to free IBU. Combinations of low doses of free IBU (250 µM) and SFN (5 µM) reduced cell viability by ~55% (P<0.01), whereas a lower dose of encapsulated IBU-SLN (62.5 µM) and free SFN (5 µM) reduced cell viability by ~80% (P<0.001) for both Panc-1 and MIA PaCa-2 cells. These results reflect 4-fold reduction in IBU-SLN dose in combination compared to free IBU. Moreover, IBU-SLN and free SFN combination reduced number of colonies by ~50% (P<0.01). Further, IBU-SLN and SFN combinations showed down-regulation of DNA binding activity of the p50 subunit of NF-κB. In conclusion, these preliminary results demonstrate the potential of IBU as a chemopreventive agent against pancreatic cancer. Furthermore, when encapsulated in nanotechnology-based SLN delivery systems and delivered in combination with SFN provide evidence of a promising approach for pancreatic cancer prevention and therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Grandhi BK, Thakkar A, Wang J and Prabhu S: A novel combinatorial nanotechnology-based oral chemopreventive regimen demonstrates significant suppression of pancreatic cancer neoplastic lesions. Cancer Prev Res. 6:1015–1025. 2013. View Article : Google Scholar

3 

Chaudhary A, Sutaria D, Huang Y, Wang J and Prabhu S: Chemoprevention of colon cancer in a rat carcinogenesis model using a novel nanotechnology-based combined treatment system. Cancer Prev Res. 4:1655–1664. 2011. View Article : Google Scholar

4 

Thakkar A, Sutaria D, Grandhi BK, Wang J and Prabhu S: The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer. Oncol Rep. 29:1671–1677. 2013.PubMed/NCBI

5 

Sutaria D, Grandhi BK, Thakkar A, Wang J and Prabhu S: Chemoprevention of pancreatic cancer using solid-lipid nanoparticulate delivery of a novel aspirin, curcumin and sulforaphane drug combination regimen. Int J Oncol. 41:2260–2268. 2012.PubMed/NCBI

6 

Palayoor ST, Bump EA, Calderwood SK, Bartol S and Coleman CN: Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma cells. Clin Cancer Res. 4:763–771. 1998.PubMed/NCBI

7 

Yao M, Zhou W, Sangha S, et al: Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer. Clin Cancer Res. 11:1618–1628. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Bonelli P, Tuccillo FM, Federico A, et al: Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations. Int J Nanomed. 7:5683–5691. 2012. View Article : Google Scholar

9 

Lanas A: A review of the gastrointestinal safety data - a gastroenterologist’s perspective. Rheumatology. 49(Suppl 2): ii3–ii10. 2010. View Article : Google Scholar

10 

Mallen SR, Essex MN and Zhang R: Gastrointestinal tolerability of NSAIDs in elderly patients: a pooled analysis of 21 randomized clinical trials with celecoxib and nonselective NSAIDs. Curr Med Res Opin. 27:1359–1366. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Brigger I, Dubernet C and Couvreur P: Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev. 54:631–651. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Potta SG, Minemi S, Nukala RK, et al: Preparation and characterization of ibuprofen solid lipid nanoparticles with enhanced solubility. J Microencapsul. 28:74–81. 2011. View Article : Google Scholar

13 

Kokawa A, Kondo H, Gotoda T, et al: Increased expression of cyclooxygenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors. Cancer. 91:333–338. 2001. View Article : Google Scholar : PubMed/NCBI

14 

O’Driscoll CM: Lipid-based formulations for intestinal lymphatic delivery. Eur J Pharm Sci. 15:405–415. 2002. View Article : Google Scholar

15 

Mehnert W and Mäder K: Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 47:165–196. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Matusheski NV, Juvik JA and Jeffery EH: Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli. Phytochemistry. 65:1273–1281. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Fahey JW, Haristoy X, Dolan PM, et al: Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc Natl Acad Sci USA. 99:7610–7615. 2002. View Article : Google Scholar

18 

Kuroiwa Y, Nishikawa A, Kitamura Y, et al: Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters. Cancer Lett. 241:275–280. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Chung FL, Conaway CC, Rao CV and Reddy BS: Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis. 21:2287–2291. 2000. View Article : Google Scholar

20 

Kallifatidis G, Rausch V, Baumann B, et al: Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced anti-apoptotic signalling. Gut. 58:949–963. 2009. View Article : Google Scholar

21 

Sze A, Erickson D, Ren L and Li D: Zeta-potential measurement using the Smoluchowski equation and the slope of the current-time relationship in electroosmotic flow. J Colloid Interface Sci. 261:402–410. 2003. View Article : Google Scholar

22 

Petersen S, Steiniger F, Fischer D, Fahr A and Bunjes H: The physical state of lipid nanoparticles influences their effect on in vitro cell viability. Eur J Pharm Biopharm. 79:150–161. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Schöler N, Hahn H, Müller RH and Liesenfeld O: Effect of lipid matrix and size of solid lipid nanoparticles (SLN) on the viability and cytokine production of macrophages. Int J Pharm. 231:167–176. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Schöler N, Olbrich C, Tabatt K, Müller RH, Hahn H and Liesenfeld O: Surfactant, but not the size of solid lipid nanoparticles (SLN) influences viability and cytokine production of macrophages. Int J Pharm. 221:57–67. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Arnarson T and Elworthy PH: Effects of structural variations on non-ionic surfactants on micellar properties and solubilization: surfactants containing very long hydrocarbon chains. J Pharm Pharmacol. 33:141–144. 1981. View Article : Google Scholar : PubMed/NCBI

26 

Sanna V, Caria G and Mariani A: Effect of lipid nanoparticles containing fatty alcohols having different chain length on the ex vivo skin permeability of Econazole nitrate. Powder Technol. 201:32–36. 2010. View Article : Google Scholar

27 

Patil S, Sandberg A, Heckert E, Self W and Seal S: Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. Biomaterials. 28:4600–4607. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Bernfield M, Götte M, Park PW, et al: Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 68:729–777. 1999. View Article : Google Scholar

29 

Win KY and Feng SS: Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials. 26:2713–2722. 2005. View Article : Google Scholar

30 

Cheng H, Zhu JL, Zeng X, Jing Y, Zhang XZ and Zhuo RX: Targeted gene delivery mediated by folate-polyethylenimine-block-poly(ethylene glycol) with receptor selectivity. Bioconjug Chem. 20:481–487. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Al-Wadei HA, Al-Wadei MH, Ullah MF and Schuller HM: Celecoxib and GABA cooperatively prevent the progression of pancreatic cancer in vitro and in xenograft models of stress-free and stress-exposed mice. PLoS One. 7:e433762012. View Article : Google Scholar : PubMed/NCBI

32 

Mukherjee P, Basu GD, Tinder TL, et al: Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition. J Immunol. 182:216–224. 2009. View Article : Google Scholar

33 

Streicher SA, Yu H, Lu L, Kidd MS and Risch HA: Case-control study of aspirin use and risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 23:1254–1263. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Thakkar A, Chenreddy S, Wang J and Prabhu S: Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. Int J Oncol 46: 1827-1834, 2015.
APA
Thakkar, A., Chenreddy, S., Wang, J., & Prabhu, S. (2015). Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. International Journal of Oncology, 46, 1827-1834. https://doi.org/10.3892/ijo.2015.2879
MLA
Thakkar, A., Chenreddy, S., Wang, J., Prabhu, S."Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention". International Journal of Oncology 46.4 (2015): 1827-1834.
Chicago
Thakkar, A., Chenreddy, S., Wang, J., Prabhu, S."Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention". International Journal of Oncology 46, no. 4 (2015): 1827-1834. https://doi.org/10.3892/ijo.2015.2879
Copy and paste a formatted citation
x
Spandidos Publications style
Thakkar A, Chenreddy S, Wang J and Prabhu S: Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. Int J Oncol 46: 1827-1834, 2015.
APA
Thakkar, A., Chenreddy, S., Wang, J., & Prabhu, S. (2015). Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. International Journal of Oncology, 46, 1827-1834. https://doi.org/10.3892/ijo.2015.2879
MLA
Thakkar, A., Chenreddy, S., Wang, J., Prabhu, S."Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention". International Journal of Oncology 46.4 (2015): 1827-1834.
Chicago
Thakkar, A., Chenreddy, S., Wang, J., Prabhu, S."Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention". International Journal of Oncology 46, no. 4 (2015): 1827-1834. https://doi.org/10.3892/ijo.2015.2879
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team