Receptor-mediated delivery of all-trans-retinoic acid (ATRA) to hepatocytes from ATRA-loaded poly(N-p-vinylbenzyl-4-o-β-d-galactopyranosyl-d-gluconamide) nanoparticles

Seog Jin Seo, Hyun Seuk Moon, Ding Ding Guo, Sang Heon Kim, Toshihiro Akaike, Chong Su Cho

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

All-trans-retinoic acid (ATRA) plays a role in regulating CYP26 gene expression in hepatocytes. Poly(N-p-vinylbenzyl-4-o-β-d-galactopyranosyl-d-gluconamide) (PVLA) nanoparticles have been used as hepatocyte-specific targeting candidates. The objective of this study was to investigate receptor-mediated delivery of ATRA using PVLA nanoparticles. ATRA-loaded PVLA nanoparticles were confirmed by 1H-nuclear magnetic resonance (1H-NMR) and powder X-ray diffraction (XRD). In the 1H-NMR study, the proton signals of ATRA disappeared in the spectrum of ATRA-loaded PVLA nanoparticles in D2O, whereas in dimethylsulfoxide-d6, the spectrum seemed like an addition of the respective spectrum of each of the pure components. The crystalline peaks of ATRA disappeared in the XRD pattern of ATRA-loaded PVLA nanoparticles after ATRA was loaded into PVLA nanoparticles. In the measurement of size distribution, diameter of PVLA and ATRA-loaded PVLA nanoparticles in aqueous solution was 6.9 and 61.2 nm in number average, respectively. Flow cytometric analysis showed that the internalization of FITC-PVLA nanoparticles by hepatocytes in the absence of a competitive inhibitor was larger than preincubated with galactose. In reverse transcription-polymerase chain reaction (RT-PCR) analysis, ATRA-loaded PVLA nanoparticles induced CYP26A1 gene in hepatocytes in the absence of a competitive inhibitor but not preincubated with galactose. The results indicate that the ATRA-loaded PVLA nanoparticle can induce CYP26A1 gene in aqueous phase by an asialoglycoprotein receptor (ASGPR)-mediated delivery system.

Original languageEnglish
Pages (from-to)136-141
Number of pages6
JournalMaterials Science and Engineering C
Volume26
Issue number1
DOIs
Publication statusPublished - 2006 Jan

Bibliographical note

Funding Information:
This work was supported by the fund provided by Ministry of Science and Technology. We also acknowledge National Instrumentation Center for Environmental Management for giving opportunity of measurement of WAXD. H.S. Moon was supported by BK21 grant.

Keywords

  • All-trans-retinoic acid
  • Asialoglycoprotein receptor
  • CYP26A1
  • Galactose
  • Hepatocyte
  • Nanoparticle
  • Poly (N-p-vinylbenzyl-4-o-β-d-galactopyranosyl-d-gluconamide)

ASJC Scopus subject areas

  • General Medicine

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