title: Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin: mineralization and its effect on tumor targetability in vivo.
abstract: The in vivo stability and tumor targetability of self-assembled polymeric nanoparticles are crucial for effective drug delivery. In this study, to develop biostable nanoparticles with high tumor targetability, poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (PEG-HANPs) were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method. The resulting nanoparticles (M-PEG-HANPs) had a smaller size (153.7±4.5nm) than bare PEG-HANPs (265.1±9.5nm), implying that mineralization allows the formation of compact nanoparticles. Interestingly, when the mineralized nanoparticles were exposed to acidic buffer conditions (<pH6.5), their sizes increased rapidly due to dissolution of the inorganic minerals. Doxorubicin (DOX), chosen as the model anticancer drug, was effectively encapsulated into the bare and mineralized nanoparticles. For bare PEG-HANPs, DOX was released in a sustained manner and its release rate was not dependent on the pH of the solution. On the other hand, DOX release from M-PEG-HANPs was pH-dependent: i.e. DOX was slowly released from nanoparticles under physiological condition (pH7.4), whereas its release rates were much higher at mildly acidic environments (<pH6.5). From in vivo biodistribution study, it was found that M-PEG-HANPs could reach the tumor site more effectively than bare PEG-HANPs. The antitumor efficacy of DOX-loaded nanoparticles was evaluated after systemic administration into the tumor-bearing mice. Of the samples tested, the most effective antitumor efficacy was observed for DOX-loaded M-PEG-HANPs. Overall, these results suggest that M-PEG-HANPs could be a promising carrier for an anticancer drug.
authors.affiliation: Department of Polymer Science and Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hwa Seung
authors.initials: HS
authors.lastname: Han
authors.forename: Jungmin
authors.initials: J
authors.lastname: Lee
authors.forename: Hyun Ryoung
authors.initials: HR
authors.lastname: Kim
authors.forename: Su Young
authors.initials: SY
authors.lastname: Chae
authors.forename: Minwoo
authors.initials: M
authors.lastname: Kim
authors.forename: Gurusamy
authors.initials: G
authors.lastname: Saravanakumar
authors.forename: Hong Yeol
authors.initials: HY
authors.lastname: Yoon
authors.forename: Dong Gil
authors.initials: DG
authors.lastname: You
authors.forename: Hyewon
authors.initials: H
authors.lastname: Ko
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Jae Chan
authors.initials: JC
authors.lastname: Park
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D002130:Calcium Phosphates; D004337:Drug Carriers; D011092:Polyethylene Glycols; D004317:Doxorubicin; D006820:Hyaluronic Acid; C020243:calcium phosphate