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

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 hyperuricemiarelated 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 (ABNPs opt ) 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 ABNPs opt 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 ABNPs opt 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 ABNPs opt , 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 hyperuricemicrelated nephrolithiasis.

RETRACTED ARTICLE: Transdermal delivery of allopurinol-loaded nanostructured lipid carrier in the treatment of gout

“…X-ray diffractogram of ALP displayed certain diffraction peaks at 2θ equal to 11.98°, 14.76°, 17.301°, 24.33°, 25.68° and 28.11°, conforming the crystalline nature of ALP. These results were according to PXRD pattern of ALP reported in literature [5]. Likewise, stearic acid showed peaks at 2θ equal to 21.7° and 24.3°, demonstrating its crystalline nature as reported earlier in literature [50].…”

“…The FTIR spectrum of ALP demonstrated CH stretching of the pyrimidine ring, C = O stretching of the keto form of the 4 hydroxy tautomer, CH stretching in plane deformation and ring vibration [ 5 ]. Oleic acid showed asymmetric CH 2 stretching, symmetric CH 2 stretching, C = O stretching, OH stretching in plane, indicating C-O stretching and OH stretching out of plane[ 67 ].…”

“…Allopurinol (ALP) is the structural isomer of hypoxanthine and was introduced in 1946 by Elion, et al at the Burroughs–Wellcome Company [ 4 ]. It works by the inhibition of enzyme Xanthine oxidase, responsible for the formation of uric acid [ 5 ]. In 1966, it was approved by food and drug administration (FDA) for the treatment of gout and hyperuricemia and is the drug of choice and first line therapy in treatment of gout [ 6 , 7 ].…”

Topical Allopurinol-Loaded Nanostructured Lipid Carriers: A Novel Approach for Wound Healing Management

“…AP encapsulation efficiency obtained was 52.2%, and the drug loading was 4.74 mg/g. The encapsulation efficiency is comparable to that obtained for other type of nanoparticles [ 19 , 20 ]. Formulation of unloaded particles presented pH 6 and particles presented a particle diameter of 183 ± 6 nm, PdI had a value of 0.243 ± 0.03, and zeta potential was −34.8 ± 1.0 mV.…”

“…Nevertheless, the encapsulation of AP has been performed using different nanocarrier types for different therapeutic purposes. AP-loaded poly (ethyl cyanoacrylate) nanoparticles were developed and successfully tested against Trypanosoma cruzi in comparison to the free drug [ 18 ]; AP was encapsulated into bovine serum albumin nanoparticles for kidney targeting of the drug [ 19 ], or loaded into chitosan nanoparticles for sustained release of drug [ 20 ]; AP was also incorporated in sustained-release solid lipospheres intended for use in a suspension formulation and other oral dosage forms [ 21 ]. The only study related to AP encapsulation into a nanocarrier for topical application regards the preparation AP-loaded transferosomes topical gel for the alleviation of gout symptoms [ 22 ].…”