Effect of pH on the drug release rate from a new polymer–drug conjugate system

Abstract

The corresponding N-hydroximide and N-methyl-N-hydroximide of poly[ethylene-alt-(maleic anhydride)] (weight average molecular weight (M w ) of 100-500 g mol −1 ) were prepared as a new oral drug delivery system. Syntheses of N-hydroximide and N-methylhydroxamic acid of poly[ethylene-alt-(maleic anhydride)] were carried out by chemical modification of polymer with hydroxylamine and N-methylhydroxylamine, respectively, to give water-soluble polymers. These activated polymers were immobilized with ketoprofen in the presence of dicyclohexylcarbodiimide to give the corresponding water-insoluble ketoprofen conjugates. All products were characterized by elemental analysis as well as Fourier transform infrared and 1 H NMR spectra. In vitro release of ketoprofen was studied by measuring UV absorption at λ max = 260 nm as a function of time. This study demonstrated the potential use of N-hydroximide and N-methyl-N-hydroxamic acid of poly[ethylene-alt-(maleic anhydride)] as a drug delivery system. Controlled release was studied at different pH values and at different temperatures. At physiological temperature, the amount of drug released increased with increasing pH. The copolymer-drug adducts released the drug very slowly at the low pH found in the stomach thus protecting the drug from the action of high acid conditions and resident digestive enzymes. These N-hydroxamic acid polymer-drug conjugates were found to be potentially useful in the delivery of macromolecular drugs to targeted sites in the lower gastrointestinal tract and the colon area.

Biomimetic design of chelating interfaces

“…[1][2][3][4][5][6][7][8][9] In analytical chemistry, chelating polymers bearing different functional groups have been developed for the chromatographic separation or exchanging of metal ions and metalcontaining substances. [10][11][12][13][14][15] The biomedical significance of metal chelators has also been extensively exploited for applications in drug delivery, 16 iron chelation therapy, 17,18 selective inhibition of metal-containing enzymes, 18 etc. In addition, the application of interfacially chelating polymers as active packaging materials has recently been reported in which chelation by the package inhibits iron promoted oxidative degradation of nutrients, lipids, etc.…”

Two Enzyme Cooperatively Catalyzed Tandem Polymerization for the Synthesis of Polyester Containing Chiral (R)‐ or (S)‐Ibuprofen Pendants

“…Rapid Commun. 2014, 35, 1788−1794 Figure 2. a) CD spectra of poly(( S )-HAEP-co -CL) and poly(( R )-HAEP-co -CL) in ethanol; b) In vitro release of drug from the poly(( S )-HAEP-co -CL) into pH 1.2 KCl/HCl buffer or pH 7.4 phosphate buffer (with or without lipase added) at 37 °C, and c) GPC data for poly(( S )-HAEP-co -CL) before and after degradation in a mixture of THF and 2 mol L -1 HCl for 24 h.…”

“…[ 33 ] Polymeric prodrugs of NSAID are usually developed to reduce gastrointestinal side effects, properly improve solubility and achieve controlled delivery. [34][35][36][37] Recently, some examples of enzymatic synthesis of polyester prodrugs containing NSAID such as ibuprofen, ketoprofen, and naproxen have been reported by us [38][39][40][41] and other groups. [ 42 ] Most of these were polymeric prodrugs of racemic NSAID.…”

Carboxyl-functionalized magnetic microparticle carrier for isolation and identification of DNA in dairy products

“…PGMA can be easily modified, e.g., it can be hydrolyzed to vicinal diols [19], transformed to amines or oxidized to aldehydes [20]; also -SO À 3 , -N È R 3 , chelating and other functional groups can be easily introduced [21]. Modifiability of polymer microspheres is an essential condition for any prospective attachment of target enzymes and other biologically active molecules required in biomedical applications.…”