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Effect of Different Molecular Weights of Chitosan on Formulation and Evaluation of Allopurinol-Loaded Nanoparticles for Kidney Targeting and in Management of Hyperuricemic Nephrolithiasis

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Abstract

Present research study was conducted to formulate kidney-targeted allopurinol (AO)-loaded chitosan nanoparticles (ANPs) for management of hyperuricemic related nephrolithiasis. Different molecular weights of chitosan were used for fabricating ANP formulation by adopting modified ionotropic gelation method. The prepared batches were than evaluated for particle size analysis, entrapment efficiency, transmission electron microscopy, X-ray diffraction, Differential Scanning Calorimetry, in vitro release and in vivo animal study. The in vivo study depicted that post 2 h of administration of different formulations and pure drug; ANPs prepared from low molecular weight chitosan showed maximum concentration of AO in kidney signifying successful kidney targeting of drug (25.92 fold) whereas no or very less amount of AO was seen in other animal groups. Effectiveness (p < 0.01) of formulation in management of hyperuricemia-associated nephrolithiasis was also evaluated via estimation of urine pH and serum and urine uric acid levels of mice. Further histological study was also performed on kidney samples which again affirmed these results. Present investigation demonstrated that ANPs prepared from low MW chitosan depicted maximum kidney-targeting ability that might be due to its specific uptake by the kidneys as well as its higher solubility than other two polymers, which results in enhanced release rate from the formulation and also offers an efficient strategy for the management of hyperuricemic nephrolithiasis

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Abbreviations

AHNPs:

HMWC allopurinol nanoparticles

ALNPs:

LMWC allopurinol nanoparticles

AMNPs:

MWWC allopurinol nanoparticles

ANPs:

Allopurinol loaded chitosan nanoparticles

AO:

Allopurinol

DSC:

Differential scanning calorimetry

EE:

Entrapment efficiency

FTIR:

Fourier transform infrared

HMWC:

High molecular weight

HNPs:

Placebo chitosan nanoparticles (without drug) from HMWC

HPLC:

High performance liquid chromatography

LMWC:

Low molecular weight

LNPs:

Placebo chitosan nanoparticles (without drug) from LMWC

MMWC:

Medium molecular weight

MNPs:

Placebo chitosan nanoparticles (without drug) from MMWC

P-AHC:

Physical mixtures of AO: HMWC

P-ALC:

Physical mixtures of AO: LMWC

P-AMC:

Physical mixtures of AO: MMWC

PO:

Potassium oxonate

sTPP:

Sodium tripolyphosphate

UA:

Uric acid

UAS:

Serum UA

UAU:

Urinary UA

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Acknowledgements

Authors gratefully acknowledge Late Dr. Shailendra Kumar Singh, (Professor, Department of Pharmaceutical Sciences) GJU S&T, Hisar, for his guidance during the course of research project. Authors are grateful to the Coordinator, DST-FIST (Department of Pharmaceutical Sciences) GJU S&T, Hisar for HPLC and zetasizer analysis.

Funding

Author (Gurpreet Kandav) received financial support through University grants commission (RGNF), New Delhi.

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Authors and Affiliations

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

    Gurpreet Kandav, Dinesh Chandra Bhatt & Shailendra Kumar Singh

  2. Chandigarh College of Pharmacy, Sahibzada Ajit Singh Nagar, Punjab, 140307, India

    Gurpreet Kandav

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  1. Gurpreet Kandav
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  2. Dinesh Chandra Bhatt
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All the authors have made equal and substantial contribution to complete this manuscript.

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Correspondence to Gurpreet Kandav.

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In vivo animal experiments were approved by the Institutional Animal Ethics Committee, Guru Jambheshwar University of Science & Technology, Hisar, Haryana, India.

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Kandav, G., Bhatt, D.C. & Singh, S.K. Effect of Different Molecular Weights of Chitosan on Formulation and Evaluation of Allopurinol-Loaded Nanoparticles for Kidney Targeting and in Management of Hyperuricemic Nephrolithiasis. AAPS PharmSciTech 23, 144 (2022). https://doi.org/10.1208/s12249-022-02297-7

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