Release of 5‐aminosalicylic acid from bioadhesive N‐(2‐hydroxypropyl)methacrylamide copolymers by azoreductases in vitro

Abstract

N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers (11 a, b) containing side chains terminating in 5-aminosalicylic acid (5-ASA) and fucosylamine (10) were synthesized. A reactive polymeric precursor (9), a copolymer of HPMA (7) and N-methacryloylglycylglycine p-nitrophenyl ester (8), was consecutively aminolyzed with 5-[4-(2-aminoethylcarbamoyl)phenylazo)salicylic acid (6) and fucosylamine (10). The latter renders the copolymers bioadhesive in the gastrointestinal tract. The release of 5-ASA from 11 a, b was studied in vitro by incubation with cell-free extracts isolated from rat cecum, and factors influencing the degradation were determined. The rate of au, bond cleavage of 11 a, b was similar to the rate of cleavage of low-molecular-weight substrates, methyl orange and compound 6. Addition of benzyl viologen, a low potential electron carrier, increased the rate of cleavage At optimal benzyl viologen and substrate concentration ratios, a zero order release was observed. At higher substrate concentration, the rate of 5ASA release decreased. 0 1990, Hiithig & Wepf Verlag, Basel CCC 0025-116X/90/$03.00

A facile synthesis route for carboxyaryl-methacrylates: a way to obtain aromatic polyelectrolytes

“…In both cases, the observed interesting properties arise mainly from the benzoic acid moiety in the polymers. In general terms, most of the cited salicylic acid derivative polymers are aromatic polyelectrolytes [1,2,[4][5][6][7][8][9][10], due to their ionizable benzoic acid groups.…”

“…Tel./ Fax: (52-664) 623-3772; e-mail: aliceac@tectijuana.mx to polymers and were tested for pharmacological and biomedical applications when the development of polymeric drugs was envisioned. Some examples are 4-amino-, 4-chloro-and 4-bromosalicylic acid -formaldehyde polymers [1]; 5-aminosalicylic acid linked by an azo bond to polysulfonilamine [2]; p-amino salicylate of polyvinylalcohol [3]; 4-and 5-aminosalicylic acid linked to polyacrylates [4]; copolymers including 5-aminosalicylic acid linked through an aromatic azo bond to acrylates [5]; 4-and 5-aminosalicylic acid linked to polymethacrylates [6]; and several vinyl derivative polymers of salicylic acid [7]. However, the salicylic acid structure is also interesting, due to its functional groups.…”

Photochemical modification of the lower critical solution temperature of cinnamoylated poly(N-2-hydroxypropylmethacrylamide) in water

“…This was recently exploited for poly(N-hydroxypropylmethacrylamide) (P-HPMA), which is much discussed for drug delivery. [5] Though P-HPMA does not exhibit a LCST in water between 0 8C and 100 8C itself, partial esterification, e. g., with cinnamic acid, results in copolymers ( Fig. 1) having an LCST that can be adjusted over the full aqueous temperature range [6] .…”

In vitro release kinetics of bovine serum albumin from highly swellable dextran hydrogels

“…2,3 In the past 2 decades, many systems have been proposed to deliver drugs specifically to the colon. [4][5][6][7][8][9] Among them, dextran hydrogels are mostly preferred because they are degradable by special kinds of microbial enzymes called dextranases, which are present in the colon. [10][11][12][13] It is known that dextran is easily crosslinked with various functional organic and inorganic compounds with the formation of swollen aqueous gels.…”