title: Interconnected hyaluronic acid derivative-based nanoparticles for anticancer drug delivery.
abstract: Doxorubicin (DOX)-loaded nanoparticles (NPs) based on interconnected hyaluronic acid-ceramide (HACE) structure were fabricated and their anti-tumor efficacy was evaluated in vitro. Interconnected HACE was synthesized by cross-linking HACE with adipic acid dihydrazide (ADH) and its synthesis was identified by (1)H NMR analysis. DOX-loaded NPs with <200nm mean diameter, negative zeta potential, and spherical shape were prepared. Interconnected HACE-based NPs increased drug-loading capacity and in vitro drug release, compared to HACE-based NPs. DOX release was dependent on the environmental pH, implying the feasibility of enhancing drug release in tumor region and endosomal compartments. Synthesized interconnected HACE did not show cytotoxic effect up to 1000μg/ml concentration in NIH3T3 and MDA-MB-231 cells. In cellular uptake studies using confocal laser scanning microscopy (CLSM) and flow cytometry in MDA-MB-231 cells, higher uptake of DOX was observed in the interconnected HACE-based NPs than HACE NPs. In vitro anti-tumor efficacy was assessed by MTS-based assay, in which cytotoxic effect of DOX-loaded interconnected HACE NPs was higher than that of DOX-loaded HACE NPs. Thus, these results suggest the feasibility of interconnected HACE-based NPs to be used for efficient tumor-targeted delivery of anticancer drugs.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ju-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ubonvan
authors.initials: U
authors.lastname: Termsarasab
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Biogenics Inc., Daejeon 305-510, Republic of Korea.
authors.forename: Seung-Hak
authors.initials: SH
authors.lastname: Ko
authors.affiliation: Biogenics Inc., Daejeon 305-510, Republic of Korea; Skin & Tech Inc., Seongnam 461-713, Republic of Korea.
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Shim
authors.affiliation: College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Yoon
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: ddkim@snu.ac.kr.
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000272:Adipates / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000272:Adipates; D000970:Antineoplastic Agents; C029900:adipic acid; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: Doxorubicin; High drug payload; Hyaluronic acid-ceramide; Interconnected structure; Tumor targeting