title: Hyaluronated nanoparticles with pH- and enzyme-responsive drug release properties.
abstract: In this study, we report the development of a novel pH-responsive nanoparticle composed of hyaluronic acid (HA) grafted with functional 3-diethylaminopropyl (DEAP) groups (HA-g-DEAP). The pH-responsive nanoparticles were fabricated by a self-assembled arrangement of a hydrophilic block (HA) and a hydrophobic block (non-protonated DEAP) of HA-g-DEAP at pH 7.4. HA-g-DEAP was prepared by a simple conjugation of the carboxylic acid groups of HA and the free amine groups of DEAP. The HA-g-DEAP nanoparticles displayed pH-dependent changes in their physicochemical properties. We observed nanoparticle destabilization because of the protonation of DEAP when the pH of the solution decreased to 5.0. This phenomenon resulted in the release of the encapsulated content (model drug, doxorubicin: DOX) from the nanoparticle core. In addition, the degradation of HA by hyaluronidase (Hyal) significantly accelerated the DOX release rate, which may allow for increased drug release in diseased cells with acidic endosomal pH (∼pH 5.0) in the presence of Hyal. Overall, a significant improvement in the drug release rate was evident when this nanoparticle system was stimulated by both an acidic pH and specific enzymes.
authors: Department of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
authors: Seong Won
authors: SW
authors: Kim
authors: College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 155-756, Republic of Korea.
authors: Kyung Taek
authors: KT
authors: Oh
authors: School of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors: Yu Seok
authors: YS
authors: Youn
authors: Department of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon, Gyeonggi-do 420-743, Republic of Korea. Electronic address: eslee@catholic.ac.kr.
authors: Eun Seong
authors: ES
authors: Lee
mesh_terms: D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase
keywords: 3-(diethylamino)propylamine; Hyaluronic acid; Hyaluronidase-responsive nanoparticle; pH-responsive nanoparticle