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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Abbreviations

A-MNPs :

Allopurinol loaded chitosan coated magnetic nanoparticles

AP :

Allopurinol

C-MNPs :

Chitosan coated magnetic nanoparticles (without drug)

DSC:

Differential Scanning Calorimetry

FTIR:

Fourier Transform Infrared

HPLC:

High Performance Liquid Chromatography

MNPs:

Magnetic nanoparticles (without drug and polymer coating)

MWCO:

Molecular weight cut off

P-AP-CH:

Physical mixture of AP and chitosan polymer

PO:

Potassium oxonate

SUA:

Serum uric acid

TEM:

Transmission Electron Microscopy

UA:

Uric acid

UUA:

Urine uric acid

VSM:

Vibrating sample magnetometer

XO:

Xanthine oxidase

XRD:

X-Ray Diffraction

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Haryana, Hisar, 125001, India

    Gurpreet Kandav, D. C. Bhatt & Deepak Kumar Jindal

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  1. Gurpreet Kandav
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  2. D. C. Bhatt
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  3. Deepak Kumar Jindal
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Correspondence to Gurpreet Kandav.

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Kandav, G., Bhatt, D.C. & Jindal, D.K. Targeting kidneys by superparamagnetic allopurinol loaded chitosan coated nanoparticles for the treatment of hyperuricemic nephrolithiasis. DARU J Pharm Sci 27, 661–671 (2019). https://doi.org/10.1007/s40199-019-00300-4

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