Preparation and Characterization of Celecoxib Entrapped Guar Gum Nanoparticles Targeted for Oral Drug Delivery against Colon Cancer: An In-Vitro Study
The present study is an attempt to synthesize nanosized guar gum carriers encapsulating celecoxib as the chemopreventive agent for experimental colorectal cancer (CRC). Guar gum nanoparticles without celecoxib (eGGNPs) and celecoxib loaded guar gum nanoparticles (cGGNPs) were prepared by oil-in-water emulsification and in situ polymer crosslinking method. Electron microscopy, zeta potential and fourier transform infrared spectra analysis was used to affirm the size, stability and morphology of the nanoparticles. In-vitro drug release was investigated using dialysis method. Further, the effect of nanoparticles (eGGNPs & cGGNPs) was evaluated on Caco 2 colon cancer cell lines. Spherical guar gum nanoparticles were obtained in the size range of 200±6nm with zeta potential of -32.1mV indicating good stability of the GGNPs with drug loading of 30±3.2%, and drug release following zero order kinetics. The eGGNPs had no effect on Caco2 cell viability whereas the cGGNPs showed time and concentration dependent growth inhibition of Caco 2 cells. These findings suggest the successful preparation of chemopreventive nanoparticles that can be targeted as the prophylactic agent for experimental colorectal cancer.
Keywords: nanoparticles, guar gum, celecoxib, colorectal cancer, release kinetics, cytotoxicity
2. Cooper K, Squires H, Carroll C, Papaioannou D, Booth A, Logan RF, Maguire C, et al. Chemoprevention of colorectal cancer: systematic review and economic evaluation. Health and Technology Assessment 2010; 14(32):1-206.
3. American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society (2018).
4. Yeole BB. Trends in cancer incidence in esophagus, stomach, colon, rectum and liver in males in India. Asian Pac J Cancer Prev. 2008; 9:97–100.
5. NCRP. Three-year report of the population based cancer registries- 2009-2011. National cancer registry programme, Indian council of medical research (ICMR), Bangalore, India. 2013.
6. Mohandas KM. Colorectal cancer in India: controversies, enigmas and primary prevention. Indian J Gastroenterol. 2011; 30(1):3–6. doi: 10.1007/s12664-010-0076-2.
7. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009; 30(7):1073-81. doi: 10.1093/carcin/bgp127.
8. Sobolewski C, Cerella C, Dicato M, Ghibelli L, and Diederich M. The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int J Cell Biol. 2010. doi: 10.1155/2010/215158.
9. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. New Engl J Med. 2000; 342:1946–1952.
10. Rahme E, Barkun AN, Toubouti Y, Bardou M. The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence. Gastroenterol. 2003; 125:404–412.
11. Tsioulias GJ. NSAIDs and Colorectal Cancer Control: Promise and Challenges. Curr Pharmacol Rep. 2015; 1(5): 295–301. doi: 10.1007/s40495-015-0042-x.
12. Pyrko P, Soriano N, Kardosh A, Liu YT, Uddin J, Petasis NA, et al. Downregulation of survivin expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2- inhibitory analog, dimethyl-celecoxib (DMC), in tumor cells in vitro and in vivo. Mol Cancer. 2006; 5:19.
13. Smigel K. Arthritis drug approved for polyp prevention blazes trail for other prevention trials. J Natl Can Inst. 2000; 92(4):297–299. doi.org/10.1093/jnci/92.4.297.
14. Kim B. Giardiello FM. Chemoprevention in familial adenomatous polyposis. Best Pract Res Clin Gastroenterol. 2011; 25:607–622. doi: 10.1016/j.bpg.2011.08.002.
15. Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B. Celecoxib for the prevention of colorectal adenomatous polyps. New Eng J Med. 2006; 355:885–895.
16. De Vecchis R, Baldi C, Di Biase G, Ariano C, Cioppa C, Giasi A, Valente L, Cantatrione S. Cardiovascular risk associated with celecoxib or etoricoxib: A meta-analysis of randomized controlled trials which adopted comparison with placebo or naproxen. Minerva Cardioangiol. 2014; 62:437–448.
17. Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nanoparticles as drug delivery systems. Pharmacol Rep. 2012; 64:1020-1037.
18. Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018; 16:71. doi:10.1186/s12951-018-0392-8.
19. Hans ML, Lowman AM. Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid St M Sci. 2002; 6(4):319-327.
20. Al-Saidan SM, Krishnaiah YSR, Patro, S. et al. In vitro and in vivo evaluation of guar gum matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride. AAPS PharmSciTech. 2005; 6:E14. doi.org/10.1208/pt060105.
21. Sinha V, Mittal BR, Bhutani KK, Kumria R. Colonic drug delivery of 5-fluorouracil: An in vitro evaluation. Int J pharma. 2004; 269:101-108. doi.10.1016/j.ijpharm.2003.09.036.
22. Mudgil D, Barak S, Patel A, Shah N. Partially hydrolyzed guar gum as a potential prebiotic source. Int. J. Bio. Macromol. 2018; 112:207–10.
23. Thombare N, Jha U, Mishra S , Siddiqui MZ. Guar gum as a promising starting material for diverse applications: A review. Int J Biol Macromol. 2016; 88: 361–72.
24. Krishnaiah YS, Karthikeyan RS, Gouri Sankar V, Satyanarayana V. Three-layer guar gum matrix tablet formulations for oral controlled delivery of highly soluble trimetazidine dihydrochloride. J Control Release. 2002; 81(1-2):45-56.
25. Sarmah JK, Mahanta R, Bhattacharjee SK, Mahanta R, Biswas A. Controlled release of tamoxifen citrate encapsulated in cross-linked guar gum nanoparticles. Int J Bio Macromol. 2011; 49:390–96.
26. Chaurasia, Mohini & Chourasia, Manish & Jain, Nitin & Jain, Aviral & Soni, Vandana & Gupta, Yashwant & Jain, Sanjay. Cross-linked guar gum microspheres: A viable approach for improved delivery of anticancer drugs for the treatment of colorectal cancer. AAPS PharmSciTech. 2006; 7(74). doi.10.1208/pt070374.
27. Sarmah JK, Bhattacharjee SK, Mahanta R, Mahanta R. Preparation of cross-linked guar gum nanospheres containing tamoxifen citrate by single step emulsion in situ polymer cross-linking method. J Incl Phenom Macrocycl Chem. 2009; 65: 329–34. doi: 10.1007/s10847-009-9589-7.
28. Yuan H, Chen CY, Chai GH, Du YZ, Hu FQ. Improved transport and absorption through gastrointestinal tract by PEGylated solid lipid nanoparticles. Mol. Pharm. 2013;10: 1865–73.
29. Fan H, Liu G, Huang Y, Li Y, Xia Q. Development of a nanostructured lipid carrier formulation for increasing photo-stability and water solubility of phenylethyl resorcinol. Appl. Surf. Sci. 2014; 288: 193–200.
30. Saha RN, Sajeev C, Jadhav PR, Patil SP, Srinivasan N. Determination of celecoxib in pharmaceutical formulations using UV spectrophotometry and liquid chromatography. Journal of Pharmaceutical and Biomedical Analysis. 2002; 28: 741–751.
31. Tyle P. Controlled drug delivery: Fundamentals and applications. Robinson JR, Lee VHL. Dekker M. Editors. Inc., New York. 1987. 739 ISBN 0‐8247‐7588‐0. doi.org/10.1002/jps.2600770119
32. Higuchi T. Mechanism of sustained‐action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963; 52(12):1145-49. doi.org/10.1002/jps.2600521210.
33. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15(1): 25-35.
34. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1):55–63. doi: 10.1016/0022-1759(83)90303-4.
35. Clogston JD, Patri AK. Zeta potential measurement. Methods Mol Biol. 201; 697:63-70. doi: 10.1007/978-1-60327-198-1_6.
36. Mudgil D, Barak S, Khatkar BS. X-ray diffraction, IR spectroscopy and thermal characterization of partially hydrolyzed guar gum. Int J Bio Macromol. 2012; 50:1035–39.
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