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

All-trans-retinoic acid (ATRA) plays a role in regulating CYP26 gene expression in hepatocytes. Poly(N-p-vinylbenzyl-4-o-beta-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 H-1-nuclear magnetic resonance (H-1-NMR) and powder X-ray diffraction (XRD). In the H-1-NMR study, the proton signals of ATRA disappeared in the spectrum of ATRA-loaded PVLA nanoparticles in D2O, whereas in dimethylsulfoxide-d(6), 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. (c) 2005 Elsevier B.V. All rights reserved.