Synthesis and Photoproperties of a Substituted Zinc(II) Phthalocyanine-N-(2-hydroxypropyl)methacrylamide Copolymer Conjugate

In cancer photodynamic therapy (PDT), improved efficiency of photosensitizer delivery to tumors may be obtained by binding them to targetable water soluble polymeric carriers. However, attachment of photosensitizers to Macromolecular carriers may alter their spectral and photosensitizing properties. In this study, a new monosubstituted phthalocyanine derivative, N-glycyl zinc(II) 4,9,16,23-tetraaminophthalocyanine (G-TAPC-Zn) was synthesized by the reaction of zinc(II) 4,9,16,23-tetraaminophthalocyanine (TAPC-Zn) with N-tert-butoxycarbonyl-glycine N'-hydroxybenzotriazole ester followed by deprotection of the tert-butoxycarbonyl (BOC) group. G-TAPC-Zn contains an aliphatic amino group suitable for attachment to water soluble polymeric carriers. By aminolysis of a polymeric precursor, an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer containing oligopeptide (GFLG) side-chains terminated in p-nitrophenyl ester groups, with G-TAPC-Zn a polymeric derivative of the latter (P-GFLGG-TAPC-Zn) was synthesized. Spectral data indicated that in aqueous solutions P-GFLGG-TAPC-Zn formed aggregates. The degree of aggregation decreased with increasing concentration of detergents or organic solvents in buffer solutions. Consequently, the release of the drug from carrier catalyzed by thiol proteinases, papain or cathepsin B, took place only in the presence of detergents or organic solvents, i.e., under conditions with a lower probability of aggregate formation. Binding of G-TAPC-Zn to HPMA copolymers decreased the quantum yield of singlet oxygen generation from 0.24 to 0.063 and significantly increased its resistance to photobleaching.

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Synthesis of Water-Soluble Star Polymers Based on Cyclodextrins

Physiological Research ◽

10.33549/physiolres.933981 ◽

2018 ◽

pp. S357-S365

Author(s):

L. KOTRCHOVÁ ◽

T. ETRYCH

Keyword(s):

Star Polymers ◽

Water Soluble ◽

Hpma Copolymer ◽

Polymer Carriers ◽

Physico Chemical ◽

Reversible Addition ◽

Degradation Rates ◽

Hpma Copolymers ◽

Hydroxypropyl Methacrylamide ◽

Chain Transfer Polymerization

Novel star polymers based on the water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer and cyclodextrin were synthesized and the physico-chemical behavior of these precursors was studied. Semitelechelic HPMA copolymers were grafted onto the cyclodextrin core, thus forming star-like structure. Both prepared systems were designed as possible polymer carriers for the controlled release of cytostatic drugs, which after the drug release and degradation will be eliminated from the organism. Two synthesis approaches were used to obtain similar polymer carriers with different degradation rates. All the polymers were prepared by reversible addition-fragmentation chain-transfer polymerization, which guarantees low dispersity of the prepared systems.

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Pinocytic capture and exocytosis of rat immunoglobulin IgG-N-(2-hydroxy-propyl)methacrylamide copolymer conjugates by rat visceral yolk sacs cultured in vitro

Bioscience Reports ◽

10.1007/bf01116240 ◽

1986 ◽

Vol 6 (10) ◽

pp. 869-877 ◽

Cited By ~ 6

Author(s):

Ruth Duncan ◽

Hazel C. Cable ◽

Jiri Strohalm ◽

Jindřich Kopeček

Keyword(s):

Drug Carrier ◽

Yolk Sac ◽

Membrane Receptors ◽

Cellular Transport ◽

Hpma Copolymer ◽

Intracellular Degradation ◽

Hpma Copolymers ◽

Hydroxypropyl Methacrylamide ◽

Covalently Bound

Rat immunoglobulin (IgG) was covalently bound to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers via glycylglycyl spacer. The resultant conjugate, free IgG and HPMA copolymer (containing a low percentage of tyrosinamide to facilitate radiolabelling) were radioiodinated, and their rates of pinocytic uptake, intracellular degradation and exocytic release by rat visceral yolk sacs cultured in vitro were determined. Free IgG was pinocytosed rapidly by the yolk sac and some IgG was subject to intracellular proteolysis. In comparison the IgG-HPMA copolymer conjugate was captured more slowly, but faster than unmodified HPMA. IgG was also exocytosed rapidly by the yolk sac following pinocytic capture and similarly IgG-HPMA copolymer had a much higher rate of release than unmodified H PMA. Measurement of tissue accumulation of125I-labelled IgG-H PMA copolymer in the presence of increasing concentrations of non-radiolabelled IgG showed competition for membrane binding sites between the free, and polymer-bound immunoglobulin. These experiments indicate that immunoglobulins can be covalently bound to a soluble polymer developed as a drug-carrier in such a way that they can still interact with specific membrane receptors and they are subsequently subjected to specific cellular transport mechanisms.

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Water-soluble HPMA copolymer—prostaglandin E1conjugates containing a cathepsin K sensitive spacer

Journal of Drug Targeting ◽

10.1080/10611860600834219 ◽

2006 ◽

Vol 14 (6) ◽

pp. 425-435 ◽

Cited By ~ 40

Author(s):

Huaizhong Pan ◽

Pavla Kopečková ◽

Dong Wang ◽

Jiyuan Yang ◽

Scott Miller ◽

...

Keyword(s):

Cathepsin K ◽

Water Soluble ◽

Hpma Copolymer

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Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers

International Journal of Molecular Sciences ◽

10.3390/ijms22116000 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6000

Author(s):

Sara Bertuzzi ◽

Ana Gimeno ◽

Ane Martinez-Castillo ◽

Marta G. Lete ◽

Sandra Delgado ◽

...

Keyword(s):

Electron Microscopy ◽

Lectin Binding ◽

Building Blocks ◽

Cryo Electron Microscopy ◽

Hpma Copolymers ◽

Hydroxypropyl Methacrylamide ◽

Galectin 3 ◽

Nmr Methods ◽

The Individual ◽

Statistical Effects

The interaction of multi-LacNAc (Galβ1-4GlcNAc)-containing N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers with human galectin-1 (Gal-1) and the carbohydrate recognition domain (CRD) of human galectin-3 (Gal-3) was analyzed using NMR methods in addition to cryo-electron-microscopy and dynamic light scattering (DLS) experiments. The interaction with individual LacNAc-containing components of the polymer was studied for comparison purposes. For Gal-3 CRD, the NMR data suggest a canonical interaction of the individual small-molecule bi- and trivalent ligands with the lectin binding site and better affinity for the trivalent arrangement due to statistical effects. For the glycopolymers, the interaction was stronger, although no evidence for forming a large supramolecule was obtained. In contrast, for Gal-1, the results indicate the formation of large cross-linked supramolecules in the presence of multivalent LacNAc entities for both the individual building blocks and the polymers. Interestingly, the bivalent and trivalent presentation of LacNAc in the polymer did not produce such an increase, indicating that the multivalency provided by the polymer is sufficient for triggering an efficient binding between the glycopolymer and Gal-1. This hypothesis was further demonstrated by electron microscopy and DLS methods.

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Molecularly designed water soluble, intelligent, nanosize polymeric carriers

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2003.06.003 ◽

2004 ◽

Vol 277 (1-2) ◽

pp. 105-118 ◽

Cited By ~ 50

Author(s):

Erhan Pişkin

Keyword(s):

Water Soluble ◽

Polymeric Carriers

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Singlet oxygen generation by sonication using a water-soluble fullerene (C60) complex: a potential application for sonodynamic therapy

Polymer Journal ◽

10.1038/s41428-020-0390-1 ◽

2020 ◽

Vol 52 (12) ◽

pp. 1387-1394

Author(s):

Thi Lien Nguyen ◽

Risa Katayama ◽

Chie Kojima ◽

Akikazu Matsumoto ◽

Kazuhiko Ishihara ◽

...

Keyword(s):

Singlet Oxygen ◽

Potential Application ◽

Fullerene C60 ◽

Water Soluble ◽

Sonodynamic Therapy ◽

Oxygen Generation ◽

Singlet Oxygen Generation

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Impurities in Commercial Saccharin. I. Impurities Soluble in Organic Solvents

Journal of AOAC INTERNATIONAL ◽

10.1093/jaoac/59.5.1051 ◽

1976 ◽

Vol 59 (5) ◽

pp. 1051-1058 ◽

Cited By ~ 2

Author(s):

Bozidar Stavrić ◽

Raymond Klassen ◽

W Arnold

Keyword(s):

Organic Solvents ◽

Water Solution ◽

Water Soluble ◽

Chromatographic Column ◽

Gas Liquid Chromatography ◽

Sodium Saccharin ◽

Chemical Purity ◽

Liquid Chromatographic ◽

Chloroform Methanol ◽

Sodium Form

Abstract Thirteen saccharin samples used for carcinogenicity tests in animals in various laboratories were analyzed for their chemical purity. Although most of the impurities were water-soluble, some were mainly soluble in organic solvents. These impurities were extracted with chloroform-methanol from a water solution of sodium saccharin. Samples obtained as acid-saccharin were converted to the sodium form before extraction. The major impurity in commercial saccharin, o-toluenesulfonamide, was also soluble in this system. Impurities were separated by gas-liquid chromatography of the underivatized, concentrated extract. Eleven major, well separated peaks were collected from the gas chromatographic column and identified by mass spectroscopy. Some of the peaks were compared with known standards. Qualitative and quantitative differences in impurities were observed among different saccharin samples. The identified impurities (in order of appearance from the gas-liquid chromatographic column) were as follows: o-toluenesulfonamide; p-toluenesufonamide; 1,2-benzisothiazole 1,1-dioxide; 1,2-benzisothiazoline 1,1-dioxide; diphenylsulfone; o,o′-ditolylsulfone; o,m′-ditolylsulfone, o,p′-ditolylsulfone; m,p′-ditolylsulfone; p,p′-ditolylsulfone, and tetracosane.

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