Generic placeholder image

Current Indian Science

Editor-in-Chief

ISSN (Print): 2210-299X
ISSN (Online): 2210-3007

Research Article

Optimization and In Vitro Evaluation of Curcumin-loaded Calcium Alginate Microbeads using Box-Behnken Design for Colorectal Cancer

Author(s): Amit Kumar Pandey*, Udaivir Singh Sara and Harinath Dwivedi

Volume 1, 2023

Published on: 23 October, 2023

Article ID: e2210299X250021 Pages: 10

DOI: 10.2174/012210299X250021230925041855

Price: $

Abstract

Background and Objective: After lung cancer and breast cancer, colorectal cancer (CRC) is the third most common type of cancer and has the second-highest fatality rate. Curcumin is one such naturally occurring dietary compound that demonstrated promise to treat colon cancer. For that, the goal of the current study was to coat curcumin with Eudragit S100 to treat colorectal cancer in the distal intestine release. The multiparticulate dosage form can increase the solubility of curcumin in the colon environment, sustain the drug release, and protect the drug from abrupt degradation in the colon environment. All of these alterations can enhance the colon tissue levels, especially in the colon cancer cells in the patients, and thereby can enhance the utility of the therapy.

Methods: By using the ionotropic gelation technique, the formulations were made. Moreover, Design Expert 13 used a three-factor, three-level Box-Behnken design (BBD) in this work to optimize the formulation for colon-targeted drug delivery. The concentration of potassium alginate, the concentration of calcium chloride, and the curing duration were considered independent variables, and prepared microbeads were refined to study their impacts on entrapment effectiveness and particle size. Eudragit S100 was enteric coated on Calcium alginate beads with an improved core.

Results: Regarding particle size and entrapment effectiveness, respectively, the polymer concentration and curing duration had a substantial impact. The ideal concentrations of calcium chloride and potassium alginate were 15% w/v and 6% w/v, respectively, with a 20-minute curing time. With a drug entrapment efficiency of 88.4%, the improved formulation had particles with a size of 708 μm. After 12 hours, 79.23±0.32% of the drug was released following an enteric coating of Eudragit S100 of optimized calcium alginate microbeads (10% weight gain).

Conclusion: The present study conclusively demonstrates the usefulness of a Box-Behnken design in the optimization of colon-targeted formulations. To effectively treat colorectal cancer, enteric-coated calcium alginate microbeads can be administered orally to deliver curcumin precisely to the colon.

[1]
Valentine, C.I.; Richard, A.K.; Abduhl, W.B. Drug delivery to the Colon. Technology/Industry overviews; Pharma Ventures Ltd., 2004, pp. 27-30.
[2]
Ura, J.; Shirachi, D.; Ferrill, M. The chronotherapeutic approach to pharmaceutical treatment. California Pharmacist, 1992, 23, 46-53.
[3]
Minko, T. Drug targeting to the colon with lectins and neoglycoconjugates. Adv. Drug Deliv. Rev., 2004, 56(4), 491-509.
[http://dx.doi.org/10.1016/j.addr.2003.10.017] [PMID: 14969755]
[4]
Wong, K.E.; Ngai, S.C.; Chan, K.G.; Lee, L.H.; Goh, B.H.; Chuah, L.H. Curcumin nanoformulations for colorectal cancer: A review. Front. Pharmacol., 2019, 10, 152-169.
[http://dx.doi.org/10.3389/fphar.2019.00152] [PMID: 30890933]
[5]
Maria, P.; Girardi, B.; Giorgio, F.; Losurdo, G.; Ierardi, E. Curcumin and colorectal cancer: From basic to clinical evidences. Int. J. Mol. Sci., 2020, 21(7), 2359-2364.
[PMID: 32235371]
[6]
Jain, S.K.; Jain, A.; Gupta, Y.; Ahirwar, M. Design and development of hydrogel beads for targeted drug delivery to the colon. AAPS PharmSciTech, 2007, 8(3), E34-E41.
[http://dx.doi.org/10.1208/pt0803056] [PMID: 17915806]
[7]
Kundlik, G.; Pal, R.; Hitesh, B. Celecoxib loaded microbeads: A targeted drug delivery for colorectal cancer. Int. J. Curr. Pharm. Res., 2010, 2, 46-55.
[8]
Sridhar, B.K.; Srinatha, A.; Khan, M.S. Development and evaluation of pH-dependent micro beads for colon targeting. Indian J. Pharm. Sci., 2010, 72(1), 18-23.
[http://dx.doi.org/10.4103/0250-474X.62230] [PMID: 20582185]
[9]
Patel, H.; Nagle, A.; Murthy, R.S.R. Characterization of calcium alginate beads of 5-fluorouracil for colon delivery. Asian J. Pharm., 2008, 2(4), 241-245.
[http://dx.doi.org/10.4103/0973-8398.45039]
[10]
Ghosal, K.; Ghosh, D.; Das, S.K. Preparation and evaluation of naringin-loaded polycaprolactone microspheres based oral suspension using Box-Behnken design. J. Mol. Liq., 2018, 256, 49-57.
[http://dx.doi.org/10.1016/j.molliq.2018.02.024]
[11]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[12]
Das, S.K.; Yuvaraja, K.; Khanam, J.; Nanda, A. Formulation development and statistical optimization of ibuprofen-loaded polymethacrylate microspheres using response surface methodology. Chem. Eng. Res. Des., 2015, 96, 1-14.
[http://dx.doi.org/10.1016/j.cherd.2015.01.014]
[13]
Gada, S.G.; Anand, Y.; Setty, M. Design and optimization of zidovudine loaded uriddall mucilage microspheres, using box behnken method. Int. J. Pharm. Sci. Res., 2019, 1856-1864.
[14]
Bhandare, S.B.; Laddha, K.S. Optimization of extraction parameters for total flavonoids from gardenia gummifera gum resin by response surface methodology. Int. J. Pharm. Pharm. Sci., 2016, 8(11), 64-68.
[http://dx.doi.org/10.22159/ijpps.2016v8i11.11134]
[15]
Solanki, A.B.; Parikh, J.R.; Parikh, R.H. Formulation and optimization of piroxicam proniosomes by 3-factor, 3-level box-behnken design. AAPS PharmSciTech, 2007, 8(4), 43.
[http://dx.doi.org/10.1208/pt0804086] [PMID: 18181547]
[16]
Nutan, M.T.H.; Soliman, M.S.; Taha, E.I.; Khan, M.A. Optimization and characterization of controlled release multi-particulate beads coated with starch acetate. Int. J. Pharm., 2005, 294(1-2), 89-101.
[http://dx.doi.org/10.1016/j.ijpharm.2005.01.013] [PMID: 15814233]
[17]
Das, S.K.; Khanam, J.; Nanda, A. Optimization of preparation method for ketoprofen-loaded microspheres consisting polymeric blends using simplex lattice mixture design. Mater. Sci. Eng. C, 2016, 69, 598-608.
[http://dx.doi.org/10.1016/j.msec.2016.07.010] [PMID: 27612752]
[18]
Pandey, A.K.; Choudhary, N.; Rai, V.K.; Dwivedi, H.; Kymonil, K.M.; Saraf, S.A. Fabrication and evaluation of tinidazole microbeads for colon targeting. Asian Pac. J. Trop. Dis., 2012, 2, S197-S201.
[http://dx.doi.org/10.1016/S2222-1808(12)60151-0]
[19]
Li, W.; Zhou, J.; Xu, Y. Study of the in vitro cytotoxicity testing of medical devices. Biomed. Rep., 2015, 3(5), 617-620.
[http://dx.doi.org/10.3892/br.2015.481] [PMID: 26405534]
[20]
Shaikh, S.; Shaikh, J.; Naba, Y.S.; Doke, K.; Ahmed, K.; Yusufi, M. Curcumin: Reclaiming the lost ground against cancer resistance. Cancer Drug Resist., 2021, 4(2), 298-320.
[http://dx.doi.org/10.20517/cdr.2020.92] [PMID: 35582033]
[21]
The importance of IC50 determination. Available From: https://visikol.com/blog/2022/06/07/the-importance-of-ic50-determination/ (Accessed on: July 20, 2023).

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy