Targeting kidneys by superparamagnetic allopurinol loaded chitosan coated nanoparticles for the treatment of hyperuricemic nephrolithiasis

  • Gurpreet KandavEmail author
  • D. C. Bhatt
  • Deepak Kumar Jindal
Research article



The major short coming of conventional therapy system is that they can’t deliver the therapeutics specifically to a site within the body without producing nonspecific toxicity. Present research aimed at developing kidney targeted allopurinol (AP) loaded chitosan coated magnetic nanoparticles (A-MNPs) for the management of hyperuricemic nephropathy manifested in the form of nephrolithiasis.


The work includes preparation of magnetic nanoparticles by chemical co-precipitation method and evaluation of the prepared batches for particle size analysis, Transmission electron microscopy, entrapment efficiency, in-vitro release study etc. Further, FTIR spectroscopy, X-ray diffraction, Differential Scanning Calorimetry, Vibrational sample magnetometer (VSM) and in-vivo animal studies were also performed.


VSM analysis demonstrates that the prepared nanoparticles exhibit superparamagnetic magnetic behaviour which was retained even after coating by chitosan. In-vivo studies of A-MNPs showed 19.07-fold increase in kidney uptake of AP as compared to serum post 2 h of administration in mice whereas no drug was detected in kidney and serum post 2 h administration of pure drug (free-form) indicating successful targeting to kidney as well as sustained release of AP from the formulated A-MNPs. The significant (p < 0.01) effectiveness of A-MNPs in management of hyperuricemic nephrolithiasis was observed through estimating pH and uric acid levels in urine and serum samples of mice. These findings were also confirmed by histological examination of isolated kidney samples.


Present investigation signifies that a simple external magnetic field is enough for targeting allopurinol to kidneys by formulating A-MNPs which further offers an effective approach for management of hyperuricemic nephrolithiasis.

Graphical Abstract


Magnetic nanoparticles Allopurinol Chitosan Kidney targeting Nephropathy 



Allopurinol loaded chitosan coated magnetic nanoparticles




Chitosan coated magnetic nanoparticles (without drug)


Differential Scanning Calorimetry


Fourier Transform Infrared


High Performance Liquid Chromatography


Magnetic nanoparticles (without drug and polymer coating)


Molecular weight cut off


Physical mixture of AP and chitosan polymer


Potassium oxonate


Serum uric acid


Transmission Electron Microscopy


Uric acid


Urine uric acid


Vibrating sample magnetometer


Xanthine oxidase


X-Ray Diffraction



Authors express their deepest gratitude to Late Dr. Shailendra Kumar Singh, Professor, Department of Pharmaceutical Sciences, G.J.U S&T, Hisar for his valuable contribution to research work. Authors acknowledge the UGC, New Delhi for providing Rajiv Gandhi National Fellowship and Coordinator, DST-FIST, Department of Pharmaceutical Sciences, G.J.U S&T, Hisar for providing zetasizer and HPLC analysis.

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interest.


  1. 1.
    Zhou P, Sun X, Zhang Z. Kidney targeted drug delivery system. Acta Pharm Sin B. 2014;4:37–42.CrossRefGoogle Scholar
  2. 2.
    Klinenberg JR, Kippen I, Bluestone R. Hyperuricemic nephropathy: pathologic features and factors influencing urate deposition. Nephron. 1975;14:88–98.CrossRefGoogle Scholar
  3. 3.
    Abou-Elela A. Epidemiology, pathophysiology, and management of uric acid urolithiasis: a narrative review. J Adv Res. 2017;8:513–27.CrossRefGoogle Scholar
  4. 4.
    Ngo TC, Assimos DG. Uric acid nephrolithiasis: recent progress and future directions. Rev Urol. 2007;9(1):17.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Zuckerman JE, Davis ME. Targeting therapeutics to the glomerulus with nanoparticles. Adv Chronic Kidney Dis. 2013;20:500–7.CrossRefGoogle Scholar
  6. 6.
    Nosrati H, Salehiabar M, Attari E, Davaran S, Danafar H, Manjili HK. Green and one-pot surface coating of iron oxide magnetic nanoparticles with natural amino acids and biocompatibility investigation. Appl Organometal Chem. 2017;32:e4069.CrossRefGoogle Scholar
  7. 7.
    Nosrati H, Salehiabar M, Davaran S, Ramazani A, Manjili HK, Danafar H. New advances strategies for surface functionalization of iron oxide magnetic nanoparticles (IONPs). Res Chem Intermed. 2017;43:7423–42.CrossRefGoogle Scholar
  8. 8.
    Chertok B, Moffat BA, David AE, et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials. 2008;29:487–96.CrossRefGoogle Scholar
  9. 9.
    Kumar A, Jena PK, Behera S, Lockey RF, Mohapatra S, Mohapatra S. Multifunctional magnetic nanoparticles for targeted delivery. Nanomedicine. 2010;6:64–9.CrossRefGoogle Scholar
  10. 10.
    Alimohammadi S, Salehi R, Amini N, Davaran S. Synthesis and physicochemical characterization of biodegradable PLGA-based magnetic nanoparticles containing amoxicilin. Bull Kor Chem Soc. 2012;33:3225–32.CrossRefGoogle Scholar
  11. 11.
    Qu J, Liu G, Wang Y, Hong R. Preparation of Fe3O4–chitosan nanoparticles used for hyperthermia. Adv Powder Technol. 2010;21:461–7.CrossRefGoogle Scholar
  12. 12.
    Dorniani D, Hussein MZ, Kura AU, Fakurazi S, Shaari AH, Ahmad Z. Preparation of Fe3O4 magnetic nanoparticles coated withgallic acid for drug delivery. Int J Nanomedicine. 2012;7:5745.CrossRefGoogle Scholar
  13. 13.
    Bhagav P, Upadhyay H, Chandran S. Brimonidine tartrate–Eudragit long-acting nanoparticles: formulation, optimization, in vitro and in vivo evaluation. AAPS PharmSciTech. 2011;4:1087–101.CrossRefGoogle Scholar
  14. 14.
    Yadav M, Parle M, Sharma N, Dhingra S, Raina N, Jindal DK. Brain targeted oral delivery of doxycycline hydrochloride encapsulated tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice. Drug Delivery. 2017;24(1):1429–40.CrossRefGoogle Scholar
  15. 15.
    Manjili HK, Ma’mani L, Tavaddod S, Mashhadikhan M, Shafiee A, Naderi-Manesh H. D, L-sulforaphane loaded Fe3O4@ gold core shell nanoparticles: a potential sulforaphane delivery system. PLoS One. 2016;11:e0151344.CrossRefGoogle Scholar
  16. 16.
    Girotra P, Thakur A, Kumar A, Singh SK. Identification of multi-targeted anti-migraine potential of nystatin and development of its brain targeted chitosan nanoformulation. Int J Biol Macromol. 2017;96:687–96.CrossRefGoogle Scholar
  17. 17.
    Salehiabar M, Nosrati H, Davaran S, Danafar H, Manjili HK. Facile synthesis and characterization of l-aspartic acid coated iron oxide magnetic nanoparticles (IONPs) for biomedical applications. Drug Res. 2018;68:280–5.CrossRefGoogle Scholar
  18. 18.
    Kandav G, Bhatt DC, Jindal DK. Formulation and evaluation of allopurinol loaded chitosan nanoparticles. Int J Appl Pharm. 2019;11:49–52.CrossRefGoogle Scholar
  19. 19.
    Nosrati H, Salehiabar M, Davaran S, Danafar H, Manjili HK. Methotrexate-conjugated L-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells. Drug Dev Ind Pharm. 2018;44:886–94.CrossRefGoogle Scholar
  20. 20.
    Zhang Z, Liao G, Nagai T, Hou S. Mitoxantrone polybutyl cyanoacrylate nanoparticles as an anti-neoplastic targeting drug delivery system. Int J Pharm. 1996;139(1-2):1–8.CrossRefGoogle Scholar
  21. 21.
    Hou PY, Mi C, He Y, Zhang J, Wang SQ, Yu F, et al. Pallidifloside D from Smilax riparia enhanced allopurinol effects in hyperuricemia mice. Fitoterapia. 2015;105:43–8.CrossRefGoogle Scholar
  22. 22.
    Meng X, Mao Z, Li X, Zhong D, Li M, Jia Y, et al. Baicalein decreases uric acid and prevents hyperuricemic nephropathy in mice. Oncotarget. 2017;8:40305.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Halabe A, Sperling O. Uric acid nephrolithiasis. Miner Electrolyte Metab. 1994;20:424–31.PubMedGoogle Scholar
  24. 24.
    Sangameshwar, Chandramouli HM, Medikeri SS, Hiremath SG. Evaluation of antihyperuricemic activity of shodhita shilajatu on potassium oxonate induced hyperuricemic rat model. Int J Res Ayurveda Pharm. 2017;8:53–8.Google Scholar
  25. 25.
    Zhao Y, Yang X, Lu W, Liao H, Liao F. Uricase based methods for determination of uric acid in serum. Microchim Acta. 2009;164:1–6.CrossRefGoogle Scholar
  26. 26.
    Tada H, Fujisaki A, Itoh K, Suzuki T. Facile and rapid high-performance liquid chromatography method for simultaneous determination of allopurinol and oxypurinol in human serum. J Clin Pharm Ther. 2003;28:229–34.CrossRefGoogle Scholar
  27. 27.
    Degroodt JM, Bukanski BW, Srebrnik S. Multiresidue analysis of tetracyclines in kidney by HPLC and photodiode array detection. J Liq Chromatogr Relat Technol. 1993;16:3515–29.CrossRefGoogle Scholar
  28. 28.
    Nagpal K, Singh SK, Mishra DN. Formulation, optimization, in vivo pharmacokinetic, behavioral and biochemical estimations of minocycline loaded chitosan nanoparticles for enhanced brain uptake. Chem Pharm Bull. 2013;61:258–72.CrossRefGoogle Scholar
  29. 29.
    Reinders MK, Nijdam LC, van Roon EN, Movig KL, Tim LT, van de Laar MA, et al. A simple method for quantification of allopurinol and oxipurinol in human serum by high-performance liquid chromatography with UV-detection. J Pharm Biomed Anal. 2007;45:312–7.CrossRefGoogle Scholar
  30. 30.
    Kandav G, Singh SK. Review of Nanoemulsion formulation and characterization techniques. Indian J Pharm Sci. 2018;80:781–9.Google Scholar
  31. 31.
    Tayal K, Kandav G, Girotra P, Singh SK. Formulation and evaluation of chitosan coated magnetic nanoparticles of amoxicillin trihydrate. Pharm Lett. 2015;7:241–25.Google Scholar
  32. 32.
    Fazil M, Md S, Haque S, Kumar M, Baboota S, Sahni JK, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci. 2012;47:6–15.CrossRefGoogle Scholar
  33. 33.
    Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release. 1987;5:37–42.CrossRefGoogle Scholar
  34. 34.
    Chavan C, Bala P, Pal K, Kale SN. Cross-linked chitosan-dextran sulphate vehicle system for controlled release of ciprofloxacin drug: an ophthalmic application. OpenNano. 2017;2:28–36.CrossRefGoogle Scholar
  35. 35.
    Vikram S, Dhakshnamoorthy M, Vasanthakumari R, Rajamani AR, Rangarajan M, Tsuzuki T. Tuning the magnetic properties of iron oxide nanoparticles by a room-temperature air-atmosphere (RTAA) co-precipitation method. J Nanosci Nanotechnol. 2015;15:3870–8.CrossRefGoogle Scholar
  36. 36.
    Pham XN, Nguyen TP, Pham TN, Tran TT, Tran TV. Synthesis and characterization of chitosan-coated magnetite nanoparticles and their application in curcumin drug delivery. Adv Nat Sci: Nanosci Nanotechnol. 2016;7:045010.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Gurpreet Kandav
    • 1
    Email author
  • D. C. Bhatt
    • 1
  • Deepak Kumar Jindal
    • 1
  1. 1.Department of Pharmaceutical SciencesGuru Jambheshwar University of Science & TechnologyHisarIndia

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