Browsing by Author "Guu, JA"

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Poly(2-hydroxyethyl methacrylate) film as a drug delivery system for pilocarpine
(2001-07-01)
Hsiue, GH
;
Guu, JA
;
Cheng, CC
;
應用化學系
;
Department of Applied Chemistry
This work investigates pilocarpine trapped in a matrix diffusion-controlled drug delivery system using hydrophilic inserts of Poly(2-hydroxyethyl methacrylate) (pHEMA) to ensure an increased bioavailability of pilocarpine and prolong the length of time in which the medication remains in the eyes of the test subjects. The physical and chemical properties of pilocarpine were investigated to elucidate the mechanism of drug-polymer interaction and the effect on drug release behavior of controlled release polymeric devices. In vitro release studies indicated that pilocarpine continued to be released from the inserts for a 24 h period. The results of intraocular pressure tests performed on albino rabbits were consistent with the observed in vitro behavior. The pressure decrease was significant for a period longer than 48 h. It confirms that the inserts, as sustainable releasing devices, are promising carriers for ophthalmic drug delivery systems. (C) 2001 Elsevier Science Ltd. All rights reserved.
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.