[Seo-jin Park, Jeong-hyeon Lim, Jiyu Lee, Jeongmin Lee, Sangsoo Hwang, Hyunjin Kim, Seunghyun Jo, Duckhyang Shin, Sang Ho MA, Myung L. Kim & Young G. Shin]
- Polyethylene glycol (PEG) was introduced into synthetic bilirubin 3α and a PEGylated bilirubin 3α nanoparticle (BX-001N, Brixelle®) was developed for the first time.
- An in vitro microsomal stability study, in vivo PK studies with intravenous bolus (IV) and subcutaneous injection (SC), and a semi-mass balance study of BX-001N were investigated to evaluate its pharmacokinetic (PK) properties in male Sprague-Dawley (SD) rats using developed liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF/MS).
- Following IV administration at 10 or 30 mg/kg, BX-001N showed very low clearance (0.33-0.67 mL/min/kg) with predominant distribution in the vascular system (Vd = 51.73-83.02 mL/kg). BX-001N was also very stable in vitro liver microsomal stability study.
- Following SC administration at 10 or 30 mg/kg, the bioavailability of BX-001N in plasma at 10 mg/kg was around 43% and showed the less dose-proportionality at 30 mg/kg dose.
- BX-001N was mainly excreted via the urinary pathway (86.59-92.99% of total amount of parent drug in excreta; urine and feces) not via the biliary one.
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This work was supported by the [Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare] under Grant [HN21C0947].