Formulation, Optimization, and Evaluation of Allopurinol-Loaded Bovine Serum Albumin Nanoparticles for Targeting Kidney in Management of Hyperuricemic Nephrolithiasis

Formulation, optimization, and evaluation of ABNPs for kidney targeting

Abstract

The aim of present research work was to design, fabricate, optimize, and evaluate allopurinol (ALLO)-loaded bovine serum albumin nanoparticles (ABNPs) for kidney targeting of the drug and exploring the potential of fabricated ABNPs for management of hyperuricemia-related nephrolithiasis. ABNP formulation was prepared by employing desolvation technique, and its optimization was conducted by 2-factor-3-level central composite design (CCD) in order to achieve minimum particle size (PSA) and polydispersity index (PDI), maximum entrapment efficiency (EE), and zeta potential (ZP). Further, the optimized formulation (ABNPsopt) was also assessed for in vitro drug release study, TEM, DSC, XRD analysis, FTIR spectroscopy, and in vivo animal study. The in vivo study revealed that after 2 h of ABNPsopt administration, a significant concentration of ALLO was present in kidney (21.26-fold) as compared with serum while in case of standard pure drug group; no drug was seen in mice kidney and serum post 2 h administration, which indicates successful targeting of ALLO by formulating its albumin nanoparticles. Also, uric acid and pH levels were measured in serum and urine samples of mice which showed significant (P < 0.01) efficacy of ABNPsopt formulation in management of hyperuricemia-related nephrolithiasis. Histological studies on kidney samples also confirmed these outcomes. Findings of present study indicate higher kidney uptake of allopurinol from formulated ABNPsopt, which could be due to the specificity of albumin polymer for cubilin and megalin receptors, and it also serves as effective strategy in management of hyperuricemic-related nephrolithiasis.

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Abbreviations

ABNPs:

Allopurinol (ALLO)-loaded bovine serum albumin nanoparticles

ABNPsopt :

Optimized batch of ABNPs

ALLO:

Allopurinol

BSA:

Bovine serum albumin

CCD:

Central composite design

D-ABNPs:

Bovine serum albumin nanoparticles (without drug)

DLS:

Dynamic light scattering technique

DSC:

Differential scanning calorimetry

EE:

Entrapment efficiency

FTIR:

Fourier transform infrared

HPLC:

High-performance liquid chromatography

PBS:

Phosphate buffer solution

PDI:

Polydispersity index

PM:

Physical mixture of ALLO and BSA

PO:

Potassium oxonate

PSA:

Particle size

RSM:

Response surface methodology

TEM:

Transmission electron microscopy

UA:

Uric acid

XRD:

X-ray diffraction

ZP:

Zeta potential

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Acknowledgments

The authors wish to thank late Dr. Shailendra Kumar Singh, Department of Pharmaceutical Sciences (G.J. US&T, Hisar), for his extensive help throughout the study. Authors acknowledge coordinator, DST-FIST, Department of Pharmaceutical Sciences (G.J. US&T, Hisar) for providing HPLC and particle size analysis.

Funding

The authors received financial assistance from UGC (New Delhi) by providing the Rajiv Gandhi National Fellowship.

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Correspondence to Gurpreet Kandav.

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Kandav, G., Bhatt, D.C., Jindal, D.K. et al. Formulation, Optimization, and Evaluation of Allopurinol-Loaded Bovine Serum Albumin Nanoparticles for Targeting Kidney in Management of Hyperuricemic Nephrolithiasis. AAPS PharmSciTech 21, 164 (2020). https://doi.org/10.1208/s12249-020-01695-z

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Key words

  • albumin nanoparticles
  • central composite design
  • allopurinol
  • kidney targeting
  • nephropathy
  • sustained release