Bioengineering functional copolymers. III. Synthesis of biocompatible poly[(N‐isopropylacrylamide‐co‐maleic anhydride)‐g‐poly(ethylene oxide)]/poly(ethylene imine) macrocomplexes and their thermostabilization effect on the activity of the enzyme penicillin G acylase

Abstract

Stimuli‐responsive poly[(N‐isopropylacrylamide‐co‐maleic anhydride)‐g‐poly(ethylene oxide)]/poly(ethylene imine) macrobranched macrocomplexes were synthesized by (1) the radical copolymerization of N‐isopropylacrylamide and maleic anhydride with α,α′‐azobisisobutyronitrile as an initiator in 1,4‐dioxane at 65 °C under a nitrogen atmosphere, (2) the polyesterification (grafting) of prepared poly(N‐isopropylacrylamide‐co‐maleic anhydride) containing less than 20 mol % anhydride units with α‐hydroxy‐ω‐methoxy‐poly(ethylene oxide)s having different number‐average molecular weights (Mn = 4000, 10,000, or 20,000), and (3) the incorporation of macrobranched copolymers with poly(ethylene imine) (Mn = 60,000). The composition and structure of the synthesized copolymer systems were determined by Fourier transform infrared, 1H and 13C NMR spectroscopy, and chemical and elemental analyses. The important properties of the copolymer systems (e.g., the viscosity, thermal and pH sensitivities, and lower critical solution temperature behavior) changed with increases in the molecular weight, composition, and length of the macrobranched hydrophobic domains. These copolymers with reactive anhydride and carboxylic groups were used for the stabilization of penicillin G acylase (PGA). The conjugation of the enzyme with the copolymers significantly increased the thermal stability of PGA (three times at 45 °C and two times at 65 °C). © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1580–1593, 2003

Bioengineering Functional Copolymers. IX. Poly[(maleic anhydride‐co‐hexene‐1)‐g‐poly(ethylene oxide)]

“…Similar grafting reactions were previously carried out in the poly(N-isopopylacrylamide-co-MA)/PEO system. [19,20] Poly(styrene-co-MA) was esterified with 2-propanol, sec-butanol, and tertbutanol at 65 8C in tetrahydrofuran (THF) solution with 4-dimethylaminopyridine catalyst. [22,41] These authors have synthesized and characterized poly[MA-co-a-olefins(C 6-16 )]; however, esterification of these copolymers with alkyl alcohols or methoxy-PEO has not been studied by them, which discriminates our studies from theirs and provides an advance in our work over similar systems.…”

“…[15,18] The synthesis and characterization of stimuli-responsive random copolymers of MA and N-isopropylacrylamide with different compositions (MA units in copolymers 20 mol-%) and their macromolecular reactions with poly(ethylene oxide) and poly(ethylene imine) have been reported as a route to obtain new reactive amphiphilic water-soluble polymers that are potentially useful as carriers for gene delivery. [19][20][21] It has been shown that synthesized copolymers with a given composition have a low critical solution temperature (LCST) in the range of 30.2-46.4 8C at pH values of 4.0-7.4, a fact that suggests the possibility of their use in biomedical applications, especially for enzyme immobilization to increase the thermal stability and activity of penicillin G acylase. [20] Recently, Martinez et al [22] have reported the synthesis and characterization of copolymers of MA with a-olefins (C 6-16 ) by free radical polymerization and these reactions have yielded the highest molecular weight.…”

“…[19][20][21] It has been shown that synthesized copolymers with a given composition have a low critical solution temperature (LCST) in the range of 30.2-46.4 8C at pH values of 4.0-7.4, a fact that suggests the possibility of their use in biomedical applications, especially for enzyme immobilization to increase the thermal stability and activity of penicillin G acylase. [20] Recently, Martinez et al [22] have reported the synthesis and characterization of copolymers of MA with a-olefins (C 6-16 ) by free radical polymerization and these reactions have yielded the highest molecular weight. The M w and M n values display an increase with increasing alkyl-chain length of the a-olefins.…”

Bioengineering functional copolymers. XII. Interaction of boron-containing and PEO branched derivatives of poly(MA-alt-MVE) with HeLa cells

“…They are of great interest for many researchers due to their nontoxic, cell-compatible, biodegradable, stimuli-responsive properties, and therefore, a wide range of biomedical and bioengineering applications exist as drug or enzyme carriers and biomacromolecular conjugates both in diagnostics and chemotherapy as effective antitumor agents [1][2][3][4][5][6][7][8]. It is known that these copolymers can be regarded as pre-activated polymers due to the presence of anhydride moieties susceptible to the reaction with a primary amine of a biomolecule [9].…”

Synthesis, Characterisation and Antibacterial Activity of Copolymer (N-Vinylpyrrolidone – Maleic Anhydride) With N- Diethylethanolamine

“…Antitumor functional polymers were synthesized by reaction of poly (MA-co-VP) with hydroxyl and amino containing physiologically active compound [38][39][40]. By the intermolecular reactions of poly (MA-co-styrene) [43] and poly(MA-co-methyl methacrylate) [41] with 3,6 -diamino-10-methylacridiniumchloride (acriflavine as an antiseptic agent) in DMF and poly[(N-isopropylacrylamide-co-maleic anhydride)-g-poly(ethylene oxide)] using triethylamine as catalyst [44], new derivatives of these copolymers with antimicrobial properties were also synthesized.…”