title: Preparation and characterization of Apo2L/TNF-related apoptosis-inducing ligand-loaded human serum albumin nanoparticles with improved stability and tumor distribution.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received considerable attention as a potential anticancer agent. However, recombinant Apo2L/TRAIL has several limitations, which include a weak pharmacokinetic profile, namely, a short biological half-life and rapid renal clearance, and an inability to form a homotrimeric structure. In this research, we attempted to develop a sustained release nanoparticle (NP) formulation that stabilizes Apo2L/TRAIL and preserves its antitumor activity. Apo2L/TRAIL-loaded human serum albumin (HSA) NPs were prepared using a desolvation technique optimized by particle size, zeta-potential, and entrapment efficiency. Apo2L/TRAIL in HSA-NPs continuously released over 24 h at 37°C in phosphate buffered saline and rat plasma condition, and the biological activity of Apo2L/TRAIL-HSA-NPs was preserved (IC(50) = 67.2 ng/mL versus Apo2L/TRAIL IC(50) = 55.4 ng/mL) with negligible activity loss. Furthermore, in vivo pharmacokinetic profiles and tumor distribution demonstrated the superiority of Apo2L/TRAIL-HSA-NPs over Apo2L/TRAIL. The circulating half-life period was significantly prolonged from 9.8 to 90.7 min (9.2-fold enhancement), and drug bioavailability was clearly enhanced on the basis of area under the curve analysis (2.7-fold). And tumor distribution of Apo2L/TRAIL-HSA-NPs was also increased at 1 h after injection, which was about 14-fold (1-h point) over that of Apo2L/TRAIL. These results show that Apo2L/TRAIL-loaded HSA-NPs should be considered as potential long-acting cancer agents.
authors.affiliation: Drug Targeting Laboratory, College of Pharmacy, Sungkyunkwan University, Jangan-ku, Suwon City, Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Jiang
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
authors.forename: Chan Woong
authors.initials: CW
authors.lastname: Park
authors.forename: Sung Mook
authors.initials: SM
authors.lastname: Lim
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Jin
authors.forename: Kyung Kook
authors.initials: KK
authors.lastname: Tak
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000737:chemistry; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D012709:Serum Albumin; D053221:TNF-Related Apoptosis-Inducing Ligand