An Albumin-Enriched Nanocomplex Achieves Systemic Delivery of Clopidogrel Bisulfate to Ameliorate Renal Ischemia Reperfusion Injury in Rats

Abstract

Herein, an albumin-enriched nanocomplex was developed for the solubilization and intravascular administration of clopidogrel bisulfate (CLP). In particular, CLP nanoparticles (HS-CLP-NPs) were synthesized via an improved nab-technology method using Solutol HS-15, and bovine serum albumin (BSA) was further enriched on the nanoparticle surface forming a protein corona (BH-CLP-NPs). BH-CLP-NPs displayed an average size of 163.4 ± 10.5 nm, a zeta potential of 1.85 ± 0.03 mV, an encapsulation efficiency of 99.9%, and a drug loading capacity of 32.9%. The cumulative release of CLP from BH-CLP-NPs reached about 60% within 168 h. The pharmacokinetic study on the CLP metabolite indicated that the BSAenriched nanoparticle showed greater in vivo exposure. Pharmacodynamic studies in the renal ischemia/reperfusion injury rat model further demonstrated the renal protective effect of systemically administered BH-CLP-NPs against acute kidney injury with significantly downregulated blood urea nitrogen and creatinine levels. Overall, the albumin-enriched nanocomplexes offer a neat and efficient strategy for the development of poorly water-soluble drugs to achieve intravascular administration.

Inflammation-Targeted Drug Delivery Strategies via Albumin-Based Systems

“…Due to the low solubility of clopidogrel hydrogen sulfate, an albumin corona-enriched nanocomposite with high loading capacity was synthesized by modified Nab technology. This nanocomposite has shown improved stability and cellular uptake efficiency of rat renal tubular epithelial cells in vitro and in vivo , thereby greatly improving rat renal I/R injury . Methylprednisolone bovine serum albumin nanoparticles (ME-BSA-NPs) were prepared by solvent-chemical cross-linking method for the treatment of cationic bovine serum albumin-induced membranous glomerulonephritis (MGN) .…”

“…This nanocomposite has shown improved stability and cellular uptake efficiency of rat renal tubular epithelial cells in vitro and in vivo, thereby greatly improving rat renal I/R injury. 86 Methylprednisolone bovine serum albumin nanoparticles (ME-BSA-NPs) were prepared by solvent-chemical cross-linking method for the treatment of cationic bovine serum albumininduced membranous glomerulonephritis (MGN). 87 In another study, albumin nanoparticles targeting mesangial cells were developed for the targeted delivery of celastrol for the treatment of chronic renal diseases.…”