Preparation and characterization of Eudragit L 100-55/chitosan enteric nanoparticles containing omeprazole using general factorial design: in vitro/in vivo study

Mahboubeh Rezazadeh , Reza Safaran, Mohsen Minaiyan, Abolfazl Mostafavi

Abstract


Background and purpose: Omeprazole (OMP) is broadly used for the treatment of gastroesophageal reflux and other acid-related diseases. The current study aimed to prepare enteric-coated nanoparticles containing OMP to achieve a stable powder formulation easily prescribed in children.

Experimental approach: The nanoparticles were formed by complex coacervation method using chitosan (CTS) and Eudragit L100/55 (EU) and the impact of various formulation variables (the concentrations of EU solution and its volume ratio to CTS solution) were assessed using 32 fractional design. The mean particle size (PS), zeta potential (ZP), encapsulation efficiency (EE), and drug loading (DL) were determined. Finally, the pharmacological effects of the optimized OMP enteric nanoparticles were evaluated by an in vivo antiulcer study using Sprague-Dawley rats.

Findings/Results: The highest desirability value was for formulation F5 (containing EU concentration 4 mg/mL and EU/CTS volume ratio 2:1). PS, ZP, EE, and DL of the optimized OMP-loaded nanoparticles were confirmed 810 ± 14 nm, -38.2 ± 1.8 mV, 83.1± 4.2%, and 13.1± 1.5%, respectively. in vitro release studies showed the pH sensitivity of nanoparticles and OMP release was pH-dependent. in vivo pharmacological assessment revealed that the optimized formulation was able to protect rat stomach against ulcer formation induced by indomethacin compared to the group that received normal saline which demonstrated severe peptic ulcer and hemorrhagic spots. 

Conclusion and implication: Our results indicated that the enteric EU/CTS nanoparticles were successfully prepared via a complex coacervation method and their efficacy could be comparable with commercial OMP pellets.


Keywords


Keywords: Animal study; Chitosan; Eudragit L 100-55; Omeprazole.

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References


Festen HP, Tuynman HA, Defize J, Pals G, Frants RR, Straub JP, et al. Effect of single and repeated doses of oral omeprazole on gastric acid and pepsin secretion and fasting serum gastrin and serum pepsinogen I levels. Dig Dis Sci. 1986;31(6):561-566.

DOI: 10.1007/BF01318685.

Cederberg C, Andersson T, Skanberg I. Omeprazole: pharmacokinetics and metabolism in man. Scand J Gastroenterol Suppl. 1989;24:33-40.

DOI: 10.3109/00365528909091241.

Hermans K, den Plas DV, Everaert A, Weyenberg W, Ludwig A. Full factorial design, physicochemical characterisation and biological assessment of cyclosporine A loaded cationic nanoparticles. Eur J Pharm Biopharm. 2012;82(1):27-35.

DOI: 10.1016/j.ejpb.2012.05.003.

Jelvehgari M, Zakeri-Milani P, Siahi-Shadbad M, Loveymi B, Nokhodchi A, Azari Z, et al. Development of pH-sensitive insulin nanoparticles using Eudragit L100-55 and chitosan with different molecular weights. AAPS PharmSciTech. 2010;11(3):1237-1242.

DOI: 10.1208/s12249-010-9488-7.

Hao S, Wang B, Wang Y, Zhu L, Wang B, Guo T. Preparation of Eudragit L 100-55 enteric nanoparticles by a novel emulsion diffusion method. Colloids Surf B: Biointerfaces. 2013;108:127-133.

DOI: 10.1016/j.colsurfb.2013.02.036.

Sadashiv Alai M, Lin WJ. A novel nanoparticulate system for sustained delivery of acid-labile lansoprazole. Colloids Surf B: Biointerfaces. 2013;111:453-459.

DOI: 10.1016/j.colsurfb.2013.06.035.

Ibrahim HK, Leithy IS, Makky AA. Mucoadhesive nanoparticles as carrier systems for prolonged ocular delivery of gatifloxacin/prednisolone bitherapy. Mol Pharm. 2010;7(2):576-585.

DOI: 10.1021/mp900279c.

Bendas ER, Abdelbary AA. Instantaneous enteric nano-encapsulation of omeprazole: pharmaceutical and pharmacological evaluation. Int J Pharm. 2014;468(1-2):97-104.

DOI: 10.1016/j.ijpharm.2014.04.030.

Hao S, Wang Y, Wang B, Deng J, Liu X, Liu J. Rapid preparation of pH-sensitive polymeric nanoparticle with high loading capacity using electrospray for oral drug delivery. Mater Sci Eng C Mater Biol Appl. 2013;33(8):4562-4567.

DOI: 10.1016/j.msec.2013.07.009.

Iuga CA, Bojita M. Stability study of omeprazole. Farmacia. 2010;58(2):203-210.

Takeuchi H, Yamamoto H, Kawashima Y. Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv Drug Deliv Rev. 2001;47(1):39-54.

DOI: 10.1016/s0169-409x(00)00120-4.

Rezazadeh M, Akbari V, Amuaghae E, Emami J. Preparation and characterization of an injectable thermosensitive hydrogel for simultaneous delivery of paclitaxel and doxorubicin. Res Pharm Sci. 2018;13(3):181-191.

DOI: 10.4103/1735-5362.228918.

Minaiyan M, Sajjadi SE, Amini K. Antiulcer effects of Zataria multiflora Boiss. on indomethacin-induced gastric ulcer in rats. Avicenna J Phytomed. 2018;8(5):408-415.

Minaiyan M, Karimi F, Ghannadi A. Anti-inflammatory effect of Pistacia atlantica subsp. kurdica volatile oil and gum on acetic acid-induced acute colitis in rat. Res J Pharmacogn. 2015;2(2):1-12.

Rezazadeh M, Jafari N, Akbari V, Amirian M, Tabbakhian M, Minaiyan M, et al. A mucoadhesive thermosensitive hydrogel containing erythropoietin as a potential treatment in oral mucositis: in vitro and in vivo studies. Drug Deliv Transl Res. 2018;8(5):1226-1237.

DOI: 10.1007/s13346-018-0566-9.

Cetin M, Atila A, Kadioglu Y. Formulation and in vitro characterization of Eudragit® L100 and Eudragit® L100-PLGA nanoparticles containing diclofenac sodium. AAPS PharmSciTech. 2010;11(3):1250-1256.

DOI: 10.1208/s12249-010-9489-6.

Rezazadeh M, Parandeh M, Akbari V, Ebrahimi Z, Taheri A. Incorporation of rosuvastatin-loaded chitosan/chondroitin sulfate nanoparticles into a thermosensitive hydrogel for bone tissue engineering: preparation, characterization, and cellular behavior. Pharm Dev Technol. 2019;24(3):357-367.

DOI: 10.1080/10837450.2018.1484765.

Odabasoglua F, Cakir A, Suleyman H, Asland A, Bayira Y, Halicia M, et al. Gastro protective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol. 2006;103(1):59-65.

DOI: 10.1016/j.jep.2005.06.043.


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