1. Academic Validation
  2. pH-Responsive i-motif Conjugated Hyaluronic Acid/Polyethylenimine Complexes for Drug Delivery Systems

pH-Responsive i-motif Conjugated Hyaluronic Acid/Polyethylenimine Complexes for Drug Delivery Systems

  • Pharmaceutics. 2019 May 27;11(5):247. doi: 10.3390/pharmaceutics11050247.
Gyeong Jin Lee 1 Tae-Il Kim 2 3
Affiliations

Affiliations

  • 1 Department of Biosystems & Biomaterials Science and Engineering, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. kkk347@snu.ac.kr.
  • 2 Department of Biosystems & Biomaterials Science and Engineering, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. seal1004@snu.ac.kr.
  • 3 Research Institute of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. seal1004@snu.ac.kr.
Abstract

i-motif is cytosine (C)-rich oligonucleotide (ODN) which shows pH-responsive structure change in acidic condition. Therefore, it has been utilized for the trigger of intercalated drug release, responding to environmental pH change. In this study, 2.76 molecules of i-motif binding ODNs (IBOs) were conjugated to each hyaluronic acid (HA) via amide bond linkages. Synthesis of HA-IBO conjugate (HB) was confirmed by FT-IR and Agarose gel electrophoresis with Stains-All staining. After hybridization of HB with i-motif ODN (IMO), it was confirmed that doxorubicin (DOX) could be loaded in HB-IMO hybrid structure (HBIM) with 65.6% of drug loading efficiency (DLE) and 25.0% of drug loading content (DLC). At pH 5.5, prompt and significant DOX release from HBIM was observed due to the disruption of HBIM hybrid structure via i-motif formation of IMO, contrary to pH 7.4 condition. Then, HBIM was complexed with low molecular weight polyethylenimine (PEI1.8k), forming positively charged nanostructures (Z-average size: 126.0 ± 0.4 nm, zeta-potential: 16.1 ± 0.3 mV). DOX-loaded HBIM/PEI complexes displayed higher Anticancer efficacy than free DOX in A549 cells, showing the potential for pH-responsive Anticancer drug delivery systems.

Keywords

drug delivery systems; hyaluronic acid; i-motif; nanostructure; pH-responsive; polyethylenimine.

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