title: Long-circulating self-assembled cholesteryl albumin nanoparticles enhance tumor accumulation of hydrophobic anticancer drug.
abstract: The objective of this study was to develop an albumin nanoparticle with improved stability and drug loading capacity. Generation of nanomaterials having physiologically stable and high potential for drug delivery is still challenging. Herein we synthesized cholesteryl albumin conjugate using N,N-disuccinimidyl carbonate coupling reagent and prepared paclitaxel-loaded cholesteryl albumin nanoparticle (PTX-Chol-BSA) by self-assembly with the mean hydrodynamic diameter of 147.6±1.6nm and with high loading capacity. PTX-Chol-BSA nanoparticle showed much higher colloidal stability than a simple complex of PTX and BSA (PTX-BSA) and sustained release profile. PTX-Chol-BSA nanoparticles exhibited greater cellular uptake and cytotoxicity in B16F10 and MCF-7 cancer cell lines, as compared with PTX in Cremophor EL/ethanol (PTX-Cre/EtOH) and PTX-BSA formulations. A pharmacokinetic study in tumor-bearing mice showed that the area under the concentration-time curve (AUC0-8 h) following the administration of PTX-Chol-BSA was 1.6-2-fold higher than those following the administration of PTX-Cre/EtOH and PTX-BSA. In addition, the tumor AUC0-8 h of PTX-Chol-BSA was around 2-fold higher than that of PTX-BSA. Furthermore, in vivo antitumor efficacy results revealed that PTX-Chol-BSA nanoparticles have greater antitumor efficacy. In conclusion, we demonstrated the potential of PTX-Chol-BSA nanoparticles for anti-tumor chemotherapy, with enhanced in vitro and in vivo behaviors, as compared to PTX-BSA and PTX-Cre/EtOH.
authors.affiliation: College of Pharmacy, Gachon University, Incheon 406-799, South Korea.
authors.forename: Gantumur
authors.initials: G
authors.lastname: Battogtokh
authors.affiliation: College of Pharmacy, Gachon University, Incheon 406-799, South Korea.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Gachon University, Incheon 406-799, South Korea. Electronic address: youngtakko@gachon.ac.kr.
authors.forename: Young Tag
authors.initials: YT
authors.lastname: Ko
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; D004337:Drug Carriers; C050323:cholesterol-albumin complex; D012710:Serum Albumin, Bovine; D002784:Cholesterol; D017239:Paclitaxel
keywords: Albumin; Cholesteryl BSA conjugate; Drug delivery; Paclitaxel; Self-assembled nanoparticle