Improved Pharmacokinetics Properties for Catalase by Site‐Specific Glycosidation with Aminated Dextran

Pérez, Y.; Valdivia, Aymara; Ramírez, Héctor L.; Villalonga, Reynaldo

doi:10.1002/marc.200500291

Cited by 7 publications

(10 citation statements)

References 20 publications

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“…The conjugation yield of amine was determined by 1 H nuclear magnetic resonance (NMR) spectroscopy. 16 N-hydroxysuccinimide PLGA (PLGA-NHS) was prepared as follows. PLGA 500 mg was dissolved in dichloromethane, and 1.5 equivalents of N,N′-dicyclohexyl carbodiimide and N-hydroxysuccinimide were added.…”

Section: Synthesis Of Dexblg Block Copolymermentioning

confidence: 99%

Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

Jeong

Kim²,

Chung³

et al. 2011

IJN

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Background Polymeric micelles using amphiphilic macromolecules are promising vehicles for antitumor targeting. In this study, we prepared anticancer agent-incorporated polymeric micelles using novel block copolymer. Methods We synthesized a block copolymer composed of dextran and poly (DL-lactide-co-glycolide) (DexbLG) for antitumor drug delivery. Doxorubicin was selected as the anticancer drug, and was incorporated into polymeric micelles by dialysis. Polymeric micelles were observed by transmission electron microscopy to be spherical and smaller than 100 nm, with a narrow size distribution. The particle size of doxorubicin-incorporated polymeric micelles increased with increasing drug content. Higher initial drug feeding also increased the drug content. Results During the drug-release study, an initial burst release of doxorubicin was observed for 10 hours, and doxorubicin was continuously released over 4 days. To investigate the in vitro anticancer effects of the polymeric micelles, doxorubicin-resistant HuCC-T1 cells were treated with a very high concentration of doxorubicin. In an antiproliferation study, the polymeric micelles showed higher cytotoxicity to doxorubicin-resistant HuCC-T1 cells than free doxorubicin, indicating that the polymeric micelles were effectively engulfed by tumor cells, while free doxorubicin hardly penetrated the tumor cell membrane. On confocal laser scanning microscopy, free doxorubicin expressed very weak fluorescence intensity, while the polymeric micelles expressed strong red fluorescence. Furthermore, in flow cytometric analysis, fluorescence intensity of polymeric micelles was almost twice as high than with free doxorubicin. Conclusion DexbLG polymeric micelles incorporating doxorubicin are promising vehicles for antitumor drug targeting.

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Section: Synthesis Of Dexblg Block Copolymermentioning

confidence: 99%

Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

Jeong

Kim²,

Chung³

et al. 2011

IJN

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“…Block copolymers composed of dextran and other polymers have also been reported. Pérez et al [8] reported the improved pharmacokinetic properties of catalase-conjugated dextran. The catalase-conjugated dextran has similar architecture to block copolymer.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, dextran is known to be taken up in the intestinal tract in a specific manner [7]. Pérez et al [8] reported that catalaseconjugated dextran increases the enzymatic activity and bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Dextran/Methoxy Poly(ethylene glycol) Block Copolymer

Jeong

Kim²,

Kang

2013

Journal of Chemistry

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We synthesized a block copolymer composed of dextran and methoxy poly(ethylene glycol) (mPEG). To accomplish this, the end group of dextran was modified by reductive amination. The aminated dextran (Dextran-NH2) showed the intrinsic peaks of both dextran at 3~5.5 ppm and hexamethylene diamine at 1~2.6 ppm at1H nuclear magnetic resonance (NMR) spectrum. The amino end group of dextran was conjugated with mPEG to make the block copolymer consisting of dextran/mPEG (abbreviated as DexPEG). The synthesized aminated dextran and DexPEG were characterized using1H NMR and gel permeation chromatography (GPC). The molecular weight and conjugation yield were estimated by comparing the intensity ratio of the proton peaks of the glucose molecule (4.9 ppm and 3.3~4.0 ppm) to that of the ethylene group of mPEG (3.7 ppm). Abundant hydroxyl group in the dextran chain can be used as a source of bioactive agent conjugation.

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“…Moreover, intravenous (i.v.) administration of the conjugate to lean rats illustrated a markedly improved PK profile, with a 20‐fold longer elimination half‐life (from 0.8 to 16 h), a 171‐fold increased exposure (from 1.8 to 307 U h mL −1 ), and a 176‐fold decreased clearance (from 120 to 0.68 mL min −1 ) …”

Section: Carbohydrate Polymersmentioning

confidence: 99%

Half‐Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation

2016

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Peptides and proteins constitute a vast pool of excellent drug candidates. Evolution has equipped these molecules with superior drug-like properties such as high specificity and potency. However, native peptides and proteins suffer from an inadequate pharmacokinetic profile, and their outstanding pharmacological potential can only be realized if this issue is addressed during drug development. To overcome this challenge, a variety of half-life extension techniques relying on covalent chemical modification have been developed. These methods include PEGylation, fusion to unstructured polypeptide-based PEG mimetics, conjugation of large polysaccharides, native-like glycosylation, lipidation, fusion to albumin or the Fc domain of IgG, and derivatization with bio-orthogonal moieties that direct self-assembly. This review provides an overview of available conjugation chemistries, biophysical properties, and safety data associated with these concepts. Moreover, the effects of these modifications on peptide and protein pharmacokinetics are demonstrated through key examples.

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Improved Pharmacokinetics Properties for Catalase by Site‐Specific Glycosidation with Aminated Dextran

Cited by 7 publications

References 20 publications

Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

Synthesis of Dextran/Methoxy Poly(ethylene glycol) Block Copolymer

Half‐Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation

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