Advertisement

AAPS PharmSciTech

, 20:237 | Cite as

Budesonide-Loaded Eudragit S 100 Nanocapsules for the Treatment of Acetic Acid-Induced Colitis in Animal Model

  • Milad Reda QellinyEmail author
  • Usama Farghaly Aly
  • Omar Helmy Elgarhy
  • Khaled Aly Khaled
Research Article

Abstract

Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues as insufficient drug amount at diseased regions, high adverse effects of released drugs, and unintentionally premature drug release to noninflamed gastrointestinal regions. Herein, the prepared budesonide-loaded Eudragit S 100/Capryol 90 nanocapsules for the treatment of inflammatory bowel disease. Nanocapsules were prepared efficiently by nanoprecipitation technique and composed mainly of the pH-sensitive Eudragit S 100 polymeric coat with a semisynthetic Capryol 90 oily core. Full 31 × 21 factorial design was applied to obtain optimized nanocapsules. Optimal nanocapsules showed mean particle size of 171 nm with lower polydispersity index indicating the production of monodispersed system and negative zeta-potential of − 37.6 mV. Optimized nanocapsules showed high encapsulation efficiency of 83.4% with lower initial rapid release of 10% for first 2 h and higher rapid cumulative release of 72% after 6 h. The therapeutic activity of the prepared budesonide-loaded nanocapsules was evaluated using a rat colitis model. Disease activity score, macroscopical examination, blood glucose level, and histopathological assessment showed marked improvements over that free drug suspension. Obtained results demonstrate that the budesonide-loaded Eudragit S 100 nanocapsules are an effective colon-targeting nanosystem for the treatment of inflammatory bowel disease. Capryol 90 was found to be a successful, and even preferred, alternative to benzyl benzoate, which is commonly employed as the oil core of such nanocapsules.

KEY WORDS

Budesonide Nanocapsules Inflammatory bowel disease Capryol 90 Acetic-acid induced colitis Eudragit S 100 

Notes

Acknowledgments

Authors thank MUP (Egypt), Gattefosé (France), Cremer Oleo division (Germany), and Evonik (Germany) for generously providing gift samples. We would to greatly thank DR. Mina Ezzat for his help in the part of histopathological examination.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Rathbone MJ. In: Rathbone MJ, editor. Controlled release in Oral drug delivery, vol. 2011. New York: Springer; 2013. p. 415.Google Scholar
  2. 2.
    Philip AK, Philip B. Colon targeted drug delivery systems: a review on primary and novel approaches. Oman Med J. 2010;25(2):79–87.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Coco R, Plapied L, Pourcelle V, Jerome C, Brayden DJ, Schneider YJ, et al. Drug delivery to inflamed colon by nanoparticles: comparison of different strategies. Int J Pharm. 2013;440(1):3–12.CrossRefPubMedGoogle Scholar
  4. 4.
    Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004;53(suppl 5):v1–v16.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Hanauer SB, Robinson M, Pruitt R, Lazenby AJ, Persson T, Nilsson LG, et al. Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. Gastroenterology. 1998;115(3):525–32.CrossRefPubMedGoogle Scholar
  6. 6.
    Hua S, Marks E, Schneider JJ, Keely S. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomed : Nanotechnol Biol Med. 2015;11(5):1117–32.CrossRefGoogle Scholar
  7. 7.
    Walker BR, Colledge NR. Davidson's principles and practice of medicine e-book: With STUDENT CONSULT Online Access, 22th edition. Elsevier Health Sciences; 2013 Dec 6.Google Scholar
  8. 8.
    Wiener C, Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, selfassessment and board review. McGraw Hill Professional; 2008 Jul 20.Google Scholar
  9. 9.
    Klotz U, Schwab M. Topical delivery of therapeutic agents in the treatment of inflammatory bowel disease. Adv Drug Deliv Rev. 2005;57(2):267–79.CrossRefPubMedGoogle Scholar
  10. 10.
    Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, practice parameters committee. Am J Gastroenterol. 2004;99(7):1371–85.CrossRefPubMedGoogle Scholar
  11. 11.
    Basit AW, McConnell EL. Drug delivery to the Colon. In: Wilson CG, Crowley PJ, editors. Controlled release in Oral drug delivery. Boston: Springer US; 2011. p. 385–99.CrossRefGoogle Scholar
  12. 12.
    Sweetman SC. Martindale: the complete drug reference, 36th edition. London: Pharmaceutical press; 2009 Jun 29.Google Scholar
  13. 13.
    Ulbrich W, Lamprecht A. Targeted drug-delivery approaches by nanoparticulate carriers in the therapy of inflammatory diseases. J R Soc Interface. 2009 Nov 25;7(suppl_1):S55-66.Google Scholar
  14. 14.
    Mahajan N, Sakarkar D, Manmode A, Pathak V, Ingole R, Dewade D. Biodegradable nanoparticles for targeted delivery in treatment of ulcerative colitis. Adv Sci Lett. 2011;4(2):349–56.CrossRefGoogle Scholar
  15. 15.
    Xiao B, Merlin D. Oral colon-specific therapeutic approaches toward treatment of inflammatory bowel disease. Expert Opin Drug Deliv. 2012;9(11):1393–407.CrossRefPubMedGoogle Scholar
  16. 16.
    Collnot E-M, Ali H, Lehr C-M. Nano-and microparticulate drug carriers for targeting of the inflamed intestinal mucosa. J Control Release. 2012;161(2):235–46.CrossRefPubMedGoogle Scholar
  17. 17.
    Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm. 1989;55(1):R1–4.CrossRefGoogle Scholar
  18. 18.
    Ahmed N, Mora-Huertas C, Jaafar-Maalej C, Fessi H, Elaissari A. Polymeric drug delivery systems for encapsulating hydrophobic drugs. Drug delivery strategies for poorly water-soluble drugs. West Sussex: Wiley; 2012. p. 151–97.Google Scholar
  19. 19.
    Asfour MH, Mohsen AM. Formulation and evaluation of pH-sensitive rutin nanospheres against colon carcinoma using HCT-116 cell line. J Adv Res. 2018;9:17–26.CrossRefPubMedGoogle Scholar
  20. 20.
    Couvreur P, Barratt G, Fattal E, Vauthier C. Nanocapsule technology: a review. Crit Rev Ther Drug Carrier Syst. 2002;19(2):99–134.CrossRefPubMedGoogle Scholar
  21. 21.
    Blouza IL, Charcosset C, Sfar S, Fessi H. Preparation and characterization of spironolactone-loaded nanocapsules for paediatric use. Int J Pharm. 2006;325(1):124–31.CrossRefGoogle Scholar
  22. 22.
    Katzer TCP, Bernardi A, Pohlmann A, Guterres SS, Ruver Beck RC. Prednisolone-loaded nanocapsules as ocular drug delivery system: development, in vitro drug release and eye toxicity. J Microencapsul. 2014;31(6):519–28.CrossRefPubMedGoogle Scholar
  23. 23.
    Kshirsagar SJ, Bhalekar MR, Patel JN, Mohapatra SK, Shewale NS. Preparation and characterization of nanocapsules for colon-targeted drug delivery system. Pharm Dev Technol. 2012;17(5):607–13.CrossRefPubMedGoogle Scholar
  24. 24.
    Cruz L, Soares LU, Dalla Costa T, Mezzalira G, da Silveira NP, Guterres SS, et al. Diffusion and mathematical modeling of release profiles from nanocarriers. Int J Pharm. 2006;313(1):198–205.CrossRefPubMedGoogle Scholar
  25. 25.
    Yallapu MM, Gupta BK, Jaggi M, Chauhan SC. Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells. J Colloid Interface Sci. 2010;351(1):19–29.CrossRefPubMedGoogle Scholar
  26. 26.
    Mora-Huertas C, Fessi H, Elaissari A. Polymer-based nanocapsules for drug delivery. Int J Pharm. 2010;385(1):113–42.CrossRefPubMedGoogle Scholar
  27. 27.
    Makhlof A, Tozuka Y, Takeuchi H. pH-sensitive nanospheres for colon-specific drug delivery in experimentally induced colitis rat model. Eur J Pharm Biopharm. 2009;72(1):1–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Naeem M, Choi M, Cao J, Lee Y, Ikram M, Yoon S, et al. Colon-targeted delivery of budesonide using dual pH-and time-dependent polymeric nanoparticles for colitis therapy. Drug Des Devel Ther. 2015;9:3789.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Vandamme TF, Lenourry A, Charrueau C, Chaumeil JC. The use of polysaccharides to target drugs to the colon. Carbohydr Polym. 2002;48(3):219–31.CrossRefGoogle Scholar
  30. 30.
    Akl MA, Kartal-Hodzic A, Oksanen T, Ismael HR, Afouna MM, Yliperttula M, et al. Factorial design formulation optimization and in vitro characterization of curcumin-loaded PLGA nanoparticles for colon delivery. J Drug Deliv Sci Technol. 2016;32(Part A):10–20.CrossRefGoogle Scholar
  31. 31.
    Santos SS, Lorenzoni A, Ferreira LM, Mattiazzi J, Adams AI, Denardi LB, et al. Clotrimazole-loaded Eudragit® RS100 nanocapsules: preparation, characterization and in vitro evaluation of antifungal activity against Candida species. J Mater Sci. 2013;33(3):1389–94.Google Scholar
  32. 32.
    Varshosaz J, Emami J, Fassihi A, Tavakoli N, Minaiyan M, Ahmadi F, et al. Effectiveness of budesonide-succinate-dextran conjugate as a novel prodrug of budesonide against acetic acid-induced colitis in rats. Int J Color Dis. 2010;25(10):1159–65.CrossRefGoogle Scholar
  33. 33.
    Lamprecht A, Schäfer U, Lehr C-M. Size-dependent bioadhesion of micro-and nanoparticulate carriers to the inflamed colonic mucosa. Pharm Res. 2001;18(6):788–93.CrossRefPubMedGoogle Scholar
  34. 34.
    Beloqui A, Coco R, Alhouayek M, Solinís MÁ, Rodríguez-Gascón A, Muccioli GG, et al. Budesonide-loaded nanostructured lipid carriers reduce inflammation in murine DSS-induced colitis. Int J Pharm. 2013;454(2):775–83.CrossRefPubMedGoogle Scholar
  35. 35.
    Aslan A, Temiz M, Atik E, Polat G, Sahinler N, Besirov E, et al. Effectiveness of mesalamine and propolis in experimental colitis. Adv Ther. 2007;24(5):1085–97.CrossRefPubMedGoogle Scholar
  36. 36.
    Gorgulu S, Yagci G, Kaymakcioglu N, Özkara M, Kurt B, Ozcan A, et al. Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid–induced colitis in rats. Dig Dis Sci. 2006;51(3):480–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Dai C, Zheng C-Q, Meng F-j, Zhou Z, Sang L-x, Jiang M. VSL# 3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-κB pathway in rat model of DSS-induced colitis. Mol Cell Biochem. 2013;374(1–2):1–11.CrossRefPubMedGoogle Scholar
  38. 38.
    Yue G, Sun FF, Dunn C, Yin K, Wong P. The 21-aminosteroid tirilazad mesylate can ameliorate inflammatory bowel disease in rats. J Pharmacol Exp Ther. 1996;276(1):265–70.PubMedGoogle Scholar
  39. 39.
    Thiesen A, Wild G, Tappenden K, Drozdowski L, Keelan M, Thomson B, et al. The locally acting glucocorticosteroid budesonide enhances intestinal sugar uptake following intestinal resection in rats. Gut. 2003;52(2):252–9.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    De Lima LS, Araujo MDM, Quináia SP, Migliorine DW, Garcia JR. Adsorption modeling of Cr, cd and cu on activated carbon of different origins by using fractional factorial design. J Chem Eng J. 2011;166(3):881–9.CrossRefGoogle Scholar
  41. 41.
    Chauhan B, Gupta R. Application of statistical experimental design for optimization of alkaline protease production from Bacillus sp. RGR-14. J Process Biochem. 2004;39(12):2115–22.CrossRefGoogle Scholar
  42. 42.
    Kaushik R, Saran S, Isar J, Saxena R. Statistical optimization of medium components and growth conditions by response surface methodology to enhance lipase production by Aspergillus carneus. J Mol Catal B Enzym. 2006;40(3–4):121–6.CrossRefGoogle Scholar
  43. 43.
    Annadurai G, Ling LY, Lee J-F. Statistical optimization of medium components and growth conditions by response surface methodology to enhance phenol degradation by Pseudomonas putida. J Hazard Mater. 2008;151(1):171–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Bendas ER, Abdelbary AA. Instantaneous enteric nano-encapsulation of omeprazole: pharmaceutical and pharmacological evaluation. Int J Pharm. 2014;468(1–2):97–104.CrossRefPubMedGoogle Scholar
  45. 45.
    Singh G, Pai RS, Devi VK. Optimization of pellets containing solid dispersion prepared by extrusion/spheronization using central composite design and desirability function. J Young Pharm. 2012;4(3):146–56.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Barzegar-Jalali M, Adibkia K, Valizadeh H, Shadbad MRS, Nokhodchi A, Omidi Y, et al. Kinetic analysis of drug release from nanoparticles. J Pharm Pharm Sci. 2008;11(1):167–77.CrossRefPubMedGoogle Scholar
  47. 47.
    Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M, et al. Nanoemulsion components screening and selection: a technical note. AAPS PharmSciTech. 2009;10(1):69–76.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Dumanli I. Mechanistic studies to elucidate the role of lipid vehicles on solubility, formulation and bioavailability of poorly soluble compounds. [PhD]. USA: University of Rhode Island; 2002.Google Scholar
  49. 49.
    Bandyopadhyay S, Katare O, Singh B. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B: Biointerfaces. 2012;100:50–61.CrossRefPubMedGoogle Scholar
  50. 50.
    Flores FC, Ribeiro RF, Ourique AF, Rolim CMB, Silva CB, Pohlmann AR, et al. Nanostructured systems containing an essential oil: protection against volatilization. Química Nova. 2011;34(6):968–72.CrossRefGoogle Scholar
  51. 51.
    Dalençon F, Amjaud Y, Lafforgue C, Derouin F, Fessi H. Atovaquone and rifabutine-loaded nanocapsules: formulation studies. Int J Pharm. 1997;153(1):127–30.CrossRefGoogle Scholar
  52. 52.
    Guterres S, Fessi H, Barratt G, Devissaguet J-P, Puisieux F. Poly (DL-lactide) nanocapsules containing diclofenac: I. formulation and stability study. Int J Pharm. 1995;113(1):57–63.CrossRefGoogle Scholar
  53. 53.
    Dwivedi P, Karumbaiah KM, Das R. Nano-size polymers via precipitation of polymer solutions. In: Fakirov S, editor. Nano-size polymers: preparation, properties, applications. Cham: Springer International Publishing; 2016. p. 251–82.CrossRefGoogle Scholar
  54. 54.
    Sharma N, Madan P, Lin S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: a co-surfactant study. Asian J Pharm Sci. 2016;11(3):404–16.CrossRefGoogle Scholar
  55. 55.
    Mora-Huertas CE, Garrigues O, Fessi H, Elaissari A. Nanocapsules prepared via nanoprecipitation and emulsification–diffusion methods: comparative study. Eur J Pharm Biopharm. 2012;80(1):235–9.CrossRefPubMedGoogle Scholar
  56. 56.
    El-Kamel A, Sokar M, Al Gamal S, Naggar V. Preparation and evaluation of ketoprofen floating oral delivery system1. Int J Pharm. 2001;220(1–2):13–21.CrossRefPubMedGoogle Scholar
  57. 57.
    Calvo P, Vila-Jato JL, Alonso MJ. Evaluation of cationic polymer-coated nanocapsules as ocular drug carriers. Int J Pharm. 1997;153(1):41–50.CrossRefGoogle Scholar
  58. 58.
    Calvo P, Vila-Jato JL, Alonso MJ. Comparative in vitro evaluation of several colloidal systems, nanoparticles, nanocapsules, and nanoemulsions, as ocular drug carriers. J Pharm Sci. 1996;85(5):530–6.CrossRefPubMedGoogle Scholar
  59. 59.
    Schaffazick SR, Pohlmann AR, Dalla-Costa T, Guterres SIS. Freeze-drying polymeric colloidal suspensions: nanocapsules, nanospheres and nanodispersion. A comparative study. Eur J Pharm Biopharm. 2003;56(3):501–5.CrossRefPubMedGoogle Scholar
  60. 60.
    Asghar LFA, Chandran S. Design and evaluation of matrix base with sigmoidal release profile for colon-specific delivery using a combination of Eudragit and non-ionic cellulose ether polymers. J Drug Deliv Transl Res. 2011;1(2):132–46.CrossRefGoogle Scholar
  61. 61.
    Ran ZH, Chen C, Xiao SD. Epigallocatechin-3-gallate ameliorates rats colitis induced by acetic acid. J Biomed Pharmacother. 2008;62(3):189–96.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Milad Reda Qelliny
    • 1
    Email author
  • Usama Farghaly Aly
    • 1
  • Omar Helmy Elgarhy
    • 1
  • Khaled Aly Khaled
    • 1
  1. 1.Department of Pharmaceutics, Faculty of PharmacyMinia UniversityMiniaEgypt

Personalised recommendations