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

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.

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

“…However, in potassium oxonate-treated animal group as shown in Fig. 8, kidney damage was described by unstructured glomeruli, patchy interstitial lymphocytic and plasma cell infiltrate along with evidence of tubulitis and tubular casts which describes the successful establishment of hyperuricemic model in mice (18). D-ABNP (placebo)-treated group revealed kidney damage similar to the inducer group and did not demonstrate any healing, hence signifying no impact of excipients on the treatment procedure.…”