OPTIMIZATION AND CHARACTERIZATION OF CHITOSAN-BASED NANOPARTICLES CONTAINING METHYLPREDNISOLONE USING BOX-BEHNKEN DESIGN FOR THE TREATMENT OF CROHN’S DISEASE

  • GANESH N. SHARMA Department of Pharmacology, School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur 302017, India
  • C. H. PRAVEEN KUMAR Department of Pharmacology, School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur 302017, India
  • BIRENDRA SHRIVASTAVA Department of Pharmacology, School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur 302017, India
  • B. KUMAR Ratnam Institute of Pharmacy, Pidathapolur (V), Muthukur (M), SPSR Nellore Dt. 524346, Andhra Pradesh, India

Abstract

Objective: The present research was designed to produce methylprednisolone containing chitosan-based nanoparticles using Box-Behnken Design (BBD) and Response Surface Methodology (RSM) for optimization.


Methods: Nanostructures were prepared using the ionic gelation method with screened process parameters. According to the design, methylprednisolone chitosan-based nanoparticles (MCSNPs) were optimized using factors like methylprednisolone concentration, stirring speed and temperature whereas particle size, zeta potential and % encapsulation efficiency as responses. From the observed values of responses with confirmation location and desirability, the predicted values were very close to the observed values.


Results: Observed values for the optimized formulation have a particle size of 243±2.33 nm with an encapsulation efficiency of 79.3±7.2%. Morphology of the particles using scanning electron microscopy reveals nearly spherical shaped particles. Methylprednisolone was released in vitro in a sustained manner for about 24 h in simulated colonic fluid pH 7, pH 7.8 (Fasted state) and phosphate buffer pH 7.4, when compared to simulated colonic fluid at pH 6 (Fed state). Optimized MCSNPs followed Korsmeyer peppas kinetics with drug release mechanism as anomalous transport.


Conclusion: Application of Box-Behnken design and Response Surface Methodology using Design Expert software was successfully used in the optimization of methylprednisolone loaded chitosan-based nanoparticles with high encapsulation efficiency.

Keywords: Methylprednisolone, Chitosan, Tripolyphosphate, Crohn’s disease, Response Surface Methodology

References

1. Malchow H, Ewe K, Brandes JW. European cooperative crohn’s disease study (ECCDS): results of drug treatment. Gastroenterology 1984;86:249-66.
2. Gross V, Andus T, Caesar I, Bischoff SC, Lochs H, Tromm A, et al. Oral pH-modi?ed release budesonide versus 6-methylprednisolone in active crohn’s disease. German/ Austrian budesonide study group. Eur J Gastroenterol Hepatol 1996;8:905-9.
3. Jagdale S, Chandekar A. Site targeted press coated delivery of methylprednisolone using eudragit rs 100 and chitosan for treatment of colitis. Recent Pat Antiinfect Drug Discovery 2011;11:32-43.
4. Modigliani R, Mary JY, Simon JF. Clinical, biological, and endoscopic picture of attacks of Crohn’s disease. Evolution on prednisolone. Groupe d’Etude Therapeutique des Affections In?ammatoires Digestives. Gastroenterology 1990;98:811-8.
5. Campieri M, Ferguson A, Doe W. Oral budesonide is as effective as oral prednisolone in active Crohn’s disease. Gut 1997;41:209-14.
6. Bar Meir S, Chowers Y, Lavy A, Lavy A, Abramovitch D, Sternberg A, et al. Budesonide versus prednisone in the treatment of active crohn’s disease. The israeli budesonide study group. Gastroenterology 1998;115:835-40.
7. Pravin Patel D, Sushma Singh. Chitosan: a multifacet polymer. Int J Curr Pharm Res 2015;7:21-8.
8. Younes I, Rinaudo M. Chitin and chitosan preparation from marine sources. structure, properties, and applications. Mar Drugs 2015;13:1133-74.
9. Yi H, Wu LQ, Bentley WE, Ghodssi R, Rubloff GW, Culver JN, et al. Biofabrication with chitosan. Biomacromolecules 2005;6:2881-94.
10. Tiyaboonchai W. Chitosan nanoparticles: a promising system for drug delivery. Naresuan University J 2003;11:51-66.
11. Lin Wu, Mingyu Chen. albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes. Int J Mol Med 2017;39:851-60.
12. Zhang L, Li Y, Wang C. Synthesis of methylprednisolone loaded ibuprofen modified inulin based nanoparticles and their application for drug delivery. Mater Sci Eng C 2014;42:111-5.
13. Hwang J, Rodgers K, Oliver JC. ?-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy. Int J Nanomed 2008;3:359-71.
14. Goldstein J, Newbury DE, Joy DC, Lyman CE, Echlin P, Lifshin E, et al. Scanning electron microscopy and x-ray microanalysis. 3rd ed. Springer; 2003. p. 21-60.
15. Victor Olaitan, Cheng Shu Chaw. Desolvation conditions for the production of sulfasalazine based albumin nanoparticles: physical properties. Pharm Front 2019;1:1-15.
16. Preet Kaur S, Rao R, Hussain A, Khatkar S. Preparation and characterization of rivastigmine loaded chitosan nanoparticles. J Pharm Sci Res 2011;3:1227-32.
17. Shevchenko EV, Talapin DV, Kotov NA, O'Brien S, Murray CB. Structural diversity in binary nanoparticle superlattices. Nature 2006;439:55-9.
18. Dubes A, Parrot Lopez H, Abdelwahed W, Degobert G, Fessi H, Shahgaldian P, Coleman AW. Scanning electron microscopy and atomic force microscopy imaging of solid lipid nanoparticles derived from amphiphilic cyclodextrins. Eur J Pharm Biopharm 2003;55:279-82.
19. Patel R, Gajra B. Ganciclovir loaded chitosan nanoparticles: preparation and characterization. J Nanomed Nanotechnol 2016;7:1000411.
20. Ahdyani R, Novitasari L. Formulation and characterization of timolol maleate-loaded nanoparticles gel by ionic gelation method using chitosan and sodium alginate. Int J Appl Pharm 2019;11:48-54.
21. Ray M, Pal K, Anis A, Banthia A. Development and characterization of chitosan-based polymeric hydrogel membranes. Des Monomers Polym 2010;13:193-206.
22. Qi L, Xu Z, Jiang X, Hu C, Zou X. Preparation and antibacterial activity of chitosan nanoparticles. Carbohydr Res 2004;339:2693-700.
23. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010;67:217-23.
24. Marasini N, Yan YD, Poudel BK, Choi HG, Yong CS, Kim JO. Development and optimization of self-nano emulsifying drug delivery system with enhanced bioavailability by box-behnken design and desirability function. J Pharm Sci 2012;101:4584-96.
25. Ferreira SC, Bruns RE, Ferreira HS, Matos GD, David JM, Brandao GC, et al. Box-behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta 2007;597:179-86.
26. Gan Q, Wang T, Cochrane C, Mccarron P. Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloids Surf B Biointerfaces 2005;44:65-73.
27. Grenha A, Seijo B, Remunan Lopez C. Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 2005;25:427-37.
28. Liu H, Gao C. Preparation and properties of ionically cross-linked chitosan nanoparticles. Polym Adv Technol 2009;20:613-9.
29. Tsai ML, Bai SW, Chen RH. Cavitation effects versus stretch effects resulted in different size and polydispersity of ionotropic gelation chitosan-sodium tripolyphosphate nanoparticle. Carbohydr Polym 2008;71:448-57.
30. Carvalho EL, Grenha A, Remunan Lopez C, Alonso MJ, Seijo B. Mucosal delivery of liposome-chitosan nanoparticle complexes. Meth Enzymol 2009;465:289-312.
31. Rampino A, Borgogna M. Chitosan nanoparticles: preparation, size evolution and stability. Int J Pharm 2013;455:219-28.
32. Seong Chul Hong, Seung Yup Yo. Chitosan-based multifunctional platforms for local delivery of therapeutics. Mar Drugs 2017;15:60.
33. So?a Papadimitriou A, Dimtrios Bikiaris M. Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohydrate Polymers 2008;73:44-54.
34. Vino AB, Ramasamy P, Shanmugam V, Shanmugam A. Extraction, characterization and in vitro antioxidative potential of chitosan and sulfated chitosan from cuttlebone of sepia aculeate orbigny, 1848. Asian Pac J Trop Biomed 2012;2:S334–S341.
35. Swathi J, Apoorva C. Optimization of chitosan and cellulose acetate phthalate controlled delivery of methylprednisolone for treatment of inflammatory bowel disease. Adv Pharm Bull 2017;7:203-13.
36. Kittur FS, Prashanth KVH, Sankar KU, Tharanathan RN. Characterization of chitin, chitosan and their carboxymethyl derivatives by differential scanning calorimetry. Carbohydr Polym 2002;49:185-93.
37. Gazori T, Khoshayand MR, Azizi E, Yazdizade P, Nomani A, Haririan I. Evaluation of alginate/chitosan nanoparticles as antisense delivery vector: formulation, optimization and in vitro characterization. Carbohydr Polym 2009;77:599-606.
38. Wang W, Zhu R, Xie Q, Li A, Xiao Y, Li K, et al. Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles. Int J Nanomed 2012;7:3667-77.
39. Avadi MR, Sadeghi AM, Mohammadpour M. Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method. Nanomedicine 2010;6:58-63.
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SHARMA, G. N., KUMAR, C. H. P., SHRIVASTAVA, B., & KUMAR, B. (2019). OPTIMIZATION AND CHARACTERIZATION OF CHITOSAN-BASED NANOPARTICLES CONTAINING METHYLPREDNISOLONE USING BOX-BEHNKEN DESIGN FOR THE TREATMENT OF CROHN’S DISEASE. International Journal of Applied Pharmaceutics, 12(2), 12-23. https://doi.org/10.22159/ijap.2020v12i2.36462
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