Browsing by Author "Juang, TM"

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Nonviral gene carriers based on diblock copolymers of poly(2-ethyl-2-oxazoline) and linear polyethylenimine
(2006-05-17)
Hsiue, GH
;
Chiang, HZ
;
Wang, CH
;
Juang, TM
;
應用化學系
Diblock copolymers that consist of poly(2-ethyl-2-oxazoline) (PEOz) and linear polyethylenimine (LPEI) were prepared for use as nonviral gene carriers. The PEOz-b-LPEI copolymers were synthesized by coupling PEOz with LPEI in a thiol-disulfide exchange reaction between the sulfhydryl and pyridyl disulfide terminal groups. A polymer/DNA weight ratio (P/D) of over 12 was required to enable PEOz-b-LPEI to condense DNA completely. The DNA-condensing capability of the diblock copolymers was increased with increasing the hydrolytic degrees of the LPEI segment. The PEOz-b-LPEI polyplexes were stable in 150 mM NaCl aqueous solution and had a mean diameter around 190 nm, whereas BPEI and LPEI polyplexes formed large aggregates in the range 300-500 nm. In addition, these polyplexes exhibited the sensitivity to solution pH and were dissociated in the acidic buffers (pH <= 5.5). The results of in vitro cell viability and luciferase assay indicated that PEOz-b-LPEI showed not only low cytotoxicity but also high transfection efficiency in gene expression.
Synthesis and biological properties of antitumor-active conjugates of ADR with dextran
(2002)
Guu, JA
;
Hsiue, GH
;
Juang, TM
;
應用化學系
;
Department of Applied Chemistry
Three kinds of polymeric adriamycin (ADR) conjugates of dextran were synthesized, namely a dextran-Gly-Leu-Gly-ADR (DGLGA) conjugate with a lysosomally degradable tripeptide spacer group, a dextran-Gly-Leu-Gly-ADR-galactosamine (DGLGA-Ga) conjugate with a targeting moiety of galactosamine on DGLGA, and a dextran-C6H10-ADR (DC(6)A) conjugate with a hexamethylen spacer group. The content of the ADR moiety in the polymeric-drug conjugate was about 3 mol%. Enzyme hydrolysis of DGLGA and DC(6)A was carried out by incubation with papain. The total amount of ADR released after 48 h was 43 mol% for DGLGA and less than 1 mol% for DC(6)A. In an in vitro cytotoxicity experiment. the DGLGA-Ga conjugate has higher cytotoxic efficacy than the other conjugates for incubation with Hep-3B cells and consequently. the capability of targeting hepatoma cells of the galactosamine residue was determined. In contrast, for the incubation with SiHa cells of these conjugates, there was no significant cytotoxicity effect. The in vivo cytotoxic efficacy of each conjugate (20 mg ADR equiv./kg) against CT-26 mice colon cells implanted subcutaneously in Balb-C mice was studied. The DGLGA conjugate generated the best therapeutic effect with the presence of long-term survival (LTS) at day 50 (2/6).
Synthesis of dextran-(5-FU)-galactosamine conjugate through a tripeptide spacer group and its in vitro properties
(2000-07-01)
Guu, JA
;
Juang, TM
;
Hsiue, GH
;
Chiu, HC
;
應用化學系
In this study, conjugation of 5-fluorouracil (5-FU) and galactosamine with dextran via Glycyl-L-Leucyl-Glycine (Gly-Leu-Gly) tripeptidyl spacer was performed first by activation of dextran with p-nitrophenyl chloroformate, followed by aminolysis of Glycyl-L-Leucyl-Glycyl-5flurouracil (Gly-Leu-Gly-5-FU) and galactosamine with activated dextrans. Preparation of Gly-Leu-Gly-5-FU was carried out by sequential reactions of peptide synthesis in solution phases and coupling with 5-FU in the presence of diethylphosphoric cyanide. The release of 5-FU from the conjugates upon the exposure of polymeric prodrugs to papain implied that the attachment of 5-FU with the tripeptidyl spacer, Gly-Leu-Gly, was capable of being liberated by cathepsin B in lysosomes of targeted cells. The observation that the cytoxicity in vitro from the incubation of dextran-5-FU conjugate containing galactosamine residues with Hep-3B cells is higher than that in the void of galactosamine indicated the occurrence of specific binding of the targeting moieties with its receptors on cell membrane, leading to an enhanced cellular uptake of the conjugate via receptor-mediated endocytosis.