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Jenjob, R.,Kun, N.,Ghee, J.Y.,Shen, Z.,Wu, X.,Cho, S.K.,Lee, D.H.,Yang, S.G. Elsevier 2016 Materials Science and Engineering C Vol.61 No.-
<P>In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd3+, chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd3+ in GdDTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd3+ incubated with Ca2+ was performed by using a dialysis membrane (MWCO 100-500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of.normal rats were observed by MR imaging. The content of free Gd3+, the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd3+ were released from Gd-DTPA-Pullulan after 2 h incubation with Ca2+ and Fe2+, respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t(1/2,alpha) = 0.43 h, t(1/2,beta) = 2.32 h), much longer than 0.11 h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast (C) 2016 Elsevier B.V. All rights reserved.</P>
Davaa, Enkhzaya,Lee, Junghan,Jenjob, Ratchapol,Yang, Su-Geun American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.1
<P>In this study, we demonstrated, that the MT1-MMP-responsive peptide (sequence: GPLPLRSWGLK) and doxorubicin-conjugated poly(lactic-co-glycolic acid/poly-(styrene-alt-maleic anhydride) core/shell microparticles (PLGA/pSMA. MPs) can be applied for intrahepatic arterial injection for hepatocellular carcinoma (HCC). PLGA/pSMA MPs were prepared with a, capillary-focused microfluidic device: The particle size, observed by scanning electron microscopy (SEM), was, around 22 +/- 3 mu m. MT1-MMP-responsive peptide and doxorubicin (D-OX) were chemically conjugated with pSMA segments on the shell of MPs to form. a PLGA/pSMA-peptide-DOX complex, resulting in high encapsulation efficiency, (91.1%) and loading content (2.9%). DOX was released from PLGA/pSMA-peptide-DOX MPs in a pH-dependent manner (similar to 25% at pH 5.4 and similar to 8% at pH 7.4) and accumulated significantly in an MT1-MMP-overexpressing Hep3B cell line. An in vivo intrahepatic injection study showed localization of MPs on the hepatic vessels and hepatic lobes up to 24 h after the injection without any shunting to the lung. Moreover, MPs efficiently inhibited tumor growth of Hep3B hepatic tumor xenografted mouse models. We expect that PLGA/pSMA-peptide-DOX MPs can be Utilized as an effective intrahepatic drug delivery system for the treatment of HCC.</P>
Kim, Min-Kyoung,Lee, Ha Neul,Jenjob, Ratchapol,Lee, Junghan,Yang, Su-Geun AMERICAN CHEMICAL SOCIETY 2017 Biomacromolecules Vol. No.
<P>Recombinant human parathyroid hormone 1-34 (rhPTH 1-34) is the most potent anabolic drug recommended for patients with osteoporosis who do not respond to conventional treatment. However, subcutaneous intermittent injection is the only effective regimen due to its unusual action of mechanism. This regimen is inconvenient and is a big hurdle in clinical applications. In this study, we designed polyelectrolyte microbeads that can deliver rhPTH 1-34 in response to Cat(2+) concentration, which indicates the osteoporotic status. Dextran photopolymer was synthesized, mixed with anionic monoacrylate, and photopolymerized by passing through capillary microfluidics to obtain the microbeads. The anionic property of microbeads was confirmed by toluidine blue staining. One microbead, loaded with a 1 day dose of rhPTH 1-34 (23.4 +/- 0.9 mu g), released rhPTH 1-34 in a triggered manner following the addition of Ca2+ ion. In vitro cell study demonstrated that rhPTH 1-34 released in a pulsatile manner from the microbeads induced osteogenic markers (ALP, RUNX2, and OPN) and precipitated mineral disposition more effectively.</P>