Enhanced Oral Bioavailability of Ibrutinib Encapsulated Poly (Lactic-co- Glycolic Acid) Nanoparticles: Pharmacokinetic Evaluation in Rats

Author(s): Abdullah S. Alshetaili*, Mohammad J. Ansari*, Md. K. Anwer, Majid A. Ganaie, Muzaffar Iqbal, Saad M. Alshahrani, Ahmad S. Alalaiwe, Bader B. Alsulays, Sultan Alshehri, Abdullah Saleh Sultan.

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 6 , 2019

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Abstract:

Background: The poor oral bioavailability of newly discovered chemical entities and marketed formulations are usually related to poor aqueous solubility or poor permeability, leading to drug failure in the development phases or therapeutic failure in a clinical setting. However, advancement in drug formulations and delivery technologies have enabled scientists to improve the bioavailability of formulations by enhancing solubility or permeability.

Objective: This study reports the enhancement of the oral bioavailability of ibrutinib (IBR), a poorly soluble anticancer drug in Wistar albino rats.

Methods: IBR loaded nanoparticles were formulated through the nanoprecipitation method by utilizing poly lactide-co-glycolide (PLGA) as a safe, biodegradable and biocompatible polymer, and poloxamer or pluronic 127 as a stabilizer. Animals were administered with a dose of 10 mg/kg of IBR suspension or an equivalent amount of IBR loaded nanoparticles. Plasma samples were extracted and analyzed by state of the art UPLC-MS/MS technique. Pharmacokinetic (PK) parameters and bioavailability were calculated by non-compartmental analysis.

Results: There was an approximately 4.2-fold enhancement in the oral bioavailability of IBR-loaded nanoparticles, as compared to the pure IBR suspension. The maximum plasma concentration (Cmax; 574.31 ± 56.20 Vs 146.34 ± 5.37 ng/mL) and exposure (AUC; 2291.65 ± 263.83 vs 544.75 ± 48.33 ng* h/mL) of IBR loaded nanoparticles were significantly higher than those exhibited through pure IBR suspension.

Conclusion: The outcomes of the present study suggested the potential of PLGA nanoparticles in the enhancement of bioavailability and the therapeutic efficacy of IBR.

Keywords: IBR, PLGA, nanoparticles, bioavailability, pharmacokinetics, UPLC-MS/MS.

[1]
Al-Shahrani, S.; Ansari, M.J. Solubility evaluations of osimertinib mesylate in physiological buffers. Indo. Am. J. Pharm. Sci., 2018, 5(4), 2610-2615.
[2]
Kalepu, S.; Nekkanti, V. Insoluble drug delivery strategies: Review of recent advances and business prospects. Acta Pharm. Sin. B, 2015, 5(5), 442-453.
[3]
Li, Y.; Wang, Y.; Zhang, R.; Liu, C.; Wei, Y.; Sun, J.; He, Z.; Xu, Y.; Zhang, T. Improving the oral bioavailability of tapentadol via a carbamate prodrug approach: Synthesis, bioactivation, and pharmacokinetics. Drug Del. Transl. Res., 2018, 8, 1335-1344.
[4]
Poce, G.; Consalvi, S.; Cocozza, M.; Fernandez-Menendez, R.; Bates, R.H.; Muro, F.O.; Aguirre, D.B.; Ballell, L.; Biava, M. Pharmaceutical salt of BM635 with improved bioavailability. Eur. J. Pharm. Sci., 2017, 99, 17-23.
[5]
Ansari, M.J. Formulation and physicochemical characterization of sodium carboxy methyl cellulose and beta cyclodextrin mediated ternary inclusion complexes of silymarin. Int. J. Pharm. Sci. Res., 2016, 7(3), 984-990.
[6]
Daeihamed, M.; Haeri, A.; Ostad, S.; Akhlaghi, M.; Dadashzadeh, S. Doxorubicin-loaded liposomes: Enhancing the oral bioavailability by modulation of physicochemical characteristics. Nanomedicine, 2017, 12, 1187-1202.
[7]
Yin, Y.; Cui, F.; Mu, C.; Choi, M.; Kim, J.; Chung, S.; Shim, C.; Kim, D. Docetaxel microemulsion for enhanced oral bioavailability: preparation and in vitro and in vivo evaluation. J. Cont. Rel., 2009, 140, 86-94.
[8]
Vyas, T.K.; Shahiwala, A.; Amiji, M.M. Improved oral bioavailability and brain transport of Saquinavir upon administration in novel nanoemulsion formulations. Int. J. Pharm., 2008, 347(1), 93-101.
[9]
Ghosh, I.; Bose, S.; Vippagunta, R.; Harmon, F. Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth. Int. J. Pharm., 2011, 409(1-2), 260-268.
[10]
Ansari, M.; Anwer, M.; Jamil, S.; Al-Shdefat, R.; Ali, B.; Ahmad, M.; Ansari, M. Enhanced oral bioavailability of insulin-loaded solid lipid nanoparticles: Pharmacokinetic bioavailability of insulin-loaded solid lipid nanoparticles in diabetic rats. Drug Del., 2016, 23(6), 1972-1979.
[11]
Delie, F.; Blanco-Príeto, M. Polymeric particulates to improve oral bioavailability of peptide drugs. Molecules, 2005, 10(1), 65-80.
[12]
Abdelbary, G.; Makhlouf, A. Adoption of polymeric micelles to enhance the oral bioavailability of dexibuprofen: formulation, in-vitro evaluation and in-vivo pharmacokinetic study in healthy human volunteers. Pharm. Dev. Technol., 2014, 19(6), 717-727.
[13]
Zhang, G.; Zhang, J. Enhanced oral bioavailability of EGCG using pH-sensitive polymeric nanoparticles: Characterization and in vivo investigation on nephrotic syndrome rats. Drug Des. Devel. Ther., 2018, 12, 2509-2518.
[14]
Ahmad, N.; Ahmad, R.; Alam, M.A.; Ahmad, F.J. Enhancement of oral bioavailability of doxorubicin through surface modified biodegradable polymeric nanoparticles. Chem. Cent. J., 2018, 12(1), 65-79.
[15]
Makadia, H.K.; and Siegel, S.J. Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel), 2011, 3(3), 1377-1397.
[16]
Jain, R.A. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials, 2000, 21(23), 2475-2490.
[17]
Mir, M.; Ahmed, N.; Rehman, A.U. Recent applications of PLGA based nanostructures in drug delivery. Colloids Surf. B Biointerfaces, 2017, 159, 217-231.
[18]
Song, X.; Zhao, X.; Zhou, Y.; Li, S.; Ma, Q. Pharmacokinetics and disposition of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles. Curr. Drug Metab., 2010, 11(10), 859-869.
[19]
Martins, L.G.; Khalil, N.M.; Mainardes, R.M. PLGA nanoparticles and polysorbate-80-coated PLGA nanoparticles increase the in vitro antioxidant activity of melatonin. Curr. Drug Deliv., 2018, 15(4), 554-563.
[20]
Rafiei, P.; Haddadi, A. Pharmacokinetic consequences of PLGA nanoparticles in docetaxel drug delivery. Pharm. Nanotechnol., 2017, 5(1), 3-23.
[21]
Jin, H.; Pi, J.; Zhao, Y.; Jiang, J.; Li, T.; Zeng, X.; Yang, P.; Evans, C.E.; Cai, J. EGFR-targeting PLGA-PEG nanoparticles as a curcumin delivery system for breast cancer therapy. Nanoscale, 2017, 9(42), 16365-16374.
[22]
Alshetaili, A.S.; Anwer, M.K.; Alshahrani, S.M.; Alalaiwe, A.; Alsulays, B.B.; Ansari, M.J.; Imam, F. Sultan, Alshehri. Characteristics and anticancer properties of Sunitinib malate-loaded poly-lactic-co-glycolic acid nanoparticles against human colon cancer HT-29 cells lines. Trop. J. Pharm. Res., 2018, 17(7), 1263-1269.
[23]
Anwer, M.K.; Al-Shdefat, R.; Ezzeldin, E.; Alshahrani, S.M.; Alshetaili, A.S.; Iqbal, M. Preparation, evaluation and bioavailability studies of eudragit coated plga nanoparticles for sustained release of eluxadoline for the treatment of irritable bowel syndrome. Front. Pharmacol., 2017, 8, 844.
[24]
Badran, M.M.; Alomrani, A.H.; Harisa, G.I.; Ashour, A.E.; Kumar, A.; Yassin, A.E. Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability. Biomed. Pharmacotherapy., 2018, 106, 1461-1468.
[25]
Singh, G.; Pai, R.S. Optimized PLGA nanoparticle platform for orally dosed trans-resveratrol with enhanced bioavailability potential. Expert Opin. Drug Deliv., 2014, 11(5), 647-659.
[26]
Anzar, N.; Mirza, M.A.; Anwer, M.K.; Khuroo, T.; Alshetaili, A.S.; Alshahrani, S.M.; Meena, J.; Hasan, N.; Talegaonkar, S.; Panda, A.K.; Iqbal, Z. Preparation, evaluation and pharmacokinetic studies of spray dried PLGA polymeric submicron particles of simvastatin for the effective treatment of breast cancer. J. Mol. Liquids., 2018, 249, 609-616.
[27]
Lee, C.S.; Rattu, M.A.; and Kim, S.S. A review of a novel, Bruton’s tyrosine kinase inhibitor, ibrutinib. J. Oncol. Pharm. Pract., 2016, 22(1), 92-104.
[28]
Siu, F.Y.; Ye, S.; Lin, H.; Li, S. Galactosylated PLGA nanoparticles for the oral delivery of resveratrol: Enhanced bioavailability and in vitro anti-inflammatory activity. Int. J. Nanomedicine, 2018, 13, 4133-4144.
[29]
US Food and Drug Administration. (2013b, November 13). Ibrutinib. Retrieved from https://www.accessdata.fda.gov/drugsatfda_ docs/label/2017/205552s016lbl.pdf (Accessed on: 30th August 2018)
[30]
Imbruvica Australian product information. Available online: https://www.janssen.com/australia/sites/www_janssen_com_australia/files/prod_files/live/imbruvica_pi.pdf (Accessed on: 30th August 2018).
[31]
de Vries, R.; Smit, J.W.; Hellemans, P.; Jiao, J.; Murphy, J.; Skee, D.; Snoeys, J.; Sukbuntherng, J.; Vliegen, M.; de Zwart, L.; and Mannaert, E. Stable isotope‐labelled intravenous microdose for absolute bioavailability and effect of grapefruit juice on ibrutinib in healthy adults. Br. J. Clin. Pharmacol., 2016, 81(2), 235-245.
[32]
Shakeel, F.; Iqbal, M.; and Ezzeldin, E. Bioavailability enhancement and pharmacokinetic profile of an anticancer drug ibrutinib by self‐nanoemulsifying drug delivery system. J. Pharm. Pharmacol., 2016, 68(6), 772-780.
[33]
Qiu, Q.; Lu, M.; Li, C.; Luo, X.; Liu, X.; Hu, L.; Liu, M.; Zheng, H.; Zhang, H.; Liu, M.; and Lai, C. Novel self-assembled ibrutinib-phospholipid complex for potently peroral delivery of poorly soluble drugs with pH-Dependent solubility. AAPS PharmSciTech, 2018, 19(8), 3571-3583.
[34]
Anwer, M.K.; Jamil, S.; Ansari, M.J.; Iqbal, M.; Imam, F.; Shakeel, F. Development and evaluation of olmesartan medoxomil loaded PLGA nanoparticles. Mat. Res. Innov., 2016, 20(3), 193-197.
[35]
Ansari, M.J. Factors affecting preparation and properties of nanoparticles by nanoprecipitation method. Indo. Am. J. P. Sci., 2017, 4(12), 4854-4858.
[36]
Iqbal, M.; Shakeel, F.; and Anwer, T. Simple and sensitive UPLC-MS/MS method for high-throughput analysis of ibrutinib in rat plasma: optimization by box-behnken experimental design. J. AOAC Int., 2016, 99, 618-625.
[37]
Guo, Y.; Yang, Y.; He, L.; Sun, R.; Pu, C.; Xie, B.; He, H.; Zhang, Y.; Yin, T.; Wang, Y.; and Tang, X. Injectable sustained-release depots of PLGA microspheres for insoluble drugs prepared by hot-melt extrusion. Pharm. Res., 2017, 34(10), 2211-2222.
[38]
Jakimska, A.; Kot-Wasik, A.; Namieśnik, J. The current state-of-the-art in the determination of pharmaceutical residues in environmental matrices using hyphenated techniques. Crit. Rev. Anal. Chem., 2014, 44(3), 277-298.
[39]
Sarbu, M.; Zamfir, A. Modern separation techniques coupled to high performance mass spectrometry for glycolipid analysis. Electrophoresis, 2018, 39, 1155-1170.
[40]
Tjandrawinata, R.R.; Setiawati, E.; Yunaidi, D.A.; Santoso, I.D.; Setiawati, A.; Susanto, L.W. Bioequivalence study of 2 formulations of film-coated tablets containing a fixed dose combination of bisoprolol fumarate 5 mg and hydrochlorothiazide 6.25 mg in healthy subjects. Drug Res., 2013, 63(5), 243-249.
[41]
Joshi, G.; Kumar, A.; Sawant, K. Enhanced bioavailability and intestinal uptake of Gemcitabine HCl loaded PLGA nanoparticles after oral delivery. Eur. J. Pharm. Sci., 2014, 60, 80-89.
[42]
Joshi, G.; Kumar, A.; Sawant, K. Bioavailability enhancement, Caco-2 cells uptake and intestinal transport of orally administered lopinavir-loaded PLGA nanoparticles. Drug Del., 2016, 23(9), 3492-3504.
[43]
Zhang, H.; Xu, J. Enhanced oral bioavailability of salmeterol by loaded PLGA microspheres: preparation, in vitro, and in vivo evaluation. Drug Del., 2016, 23(1), 248-253.
[44]
Ma, Y.; Zhao, X.; Li, J.; Shen, Q. The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability. Int. J. Nanomed., 2012, 7, 559-570.
[45]
Xie, X.; Tao, Q.; Zou, Y.; Zhang, F.; Guo, M.; Wang, Y.; Wang, H.; Zhou, Q.; Yu, S. PLGA nanoparticles improve the oral bioavailability of curcumin in rats: Characterizations and mechanisms. J. Agr. Food Chem., 2011, 59, 9280-9289.
[46]
Scheers, E.; Leclercq, L.; de Jong, J.; Bode, N.; Bockx, M.; Laenen, A.; Cuyckens, F.; Skee, D.; Murphy, J.; Sukbuntherng, J.; Mannens, G. Absorption, metabolism, and excretion of oral 14C radiolabeled ibrutinib: An open-label, phase I, single-dose study in healthy men. Drug Metab. Dispos., 2015, 43(2), 289-297.
[47]
Veeraraghavan, S.; Viswanadha, S.; Thappali, S.; Govindarajulu, B.; Vakkalanka, S.; and Rangasamy, M. Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-45227 in rat plasma by LC-MS/MS: application to a pharmacokinetic study. J. Pharm. Biomed. Anal., 2015, 107, 151-158.


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Article Details

VOLUME: 15
ISSUE: 6
Year: 2019
Page: [661 - 668]
Pages: 8
DOI: 10.2174/1573412915666190314124932

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