Polymer Drugs and Polymeric Drugs X: Slow Release of 5-Fluorouracil from Biodegradable Poly(γ-Glutamic Acid) and its Benzyl Ester Matrices

Abstract

We prepared poly(γ-glutamic acid)(γ-PGA) benzyl ester(γ-PBG) by the esterification of γ-PGA and benzyl bromide and evaluated the degradation behavior and its usefulness as a drug delivery system (DDS) matrix using 5-fluorouracil (5-FU) as a model drug. γ-PBG degraded in an acidic solution gradually for up to 130 days, and degraded very slowly in a phosphate buffer solution (pH 7.4). After 150 days, the weight loss of the γ-PBG film was only 10% in a phosphate buffer solution. A slow release of 5-FU from γ-PBG films was achieved. The release rate was affected by the pH of the outer solution and the loading drug. We observed an initial burst-release on the first day, after that, the release of 5-FU was diffusion-controlled. γ-PBG may be a novel biodegradable material that may be useful in the pharmaceutical, biomedical, and agricultural fields.

Syntheses and functions of polymers based on amino acids

“…c-PGA can undergo alkaline hydrolysis by sodium hydroxide to afford c-PGA fragments with controlled molecular weights 23) . c-PGA may be applicable to polymer drugs 24) , because its benzyl ester matrices slowly release 4-fluorouracil. c-PGA powder can initiate the cationic polymerization of N-vinylcarbazol and N-vinylpyrrolidone 25) .…”

Occurrence, functions and biosynthesis of polyamides in microorganisms and biotechnological production

“…Employing B. subtilis strain F-02-1, PGA is at present biotechnologically produced by the Japanese company Meiji Seika Kaisha Ltd. Great efforts have been made to synthesize derivatives of PGA chemically. Chemical esterifications with methyl, ethyl and benzyl groups at the α-carboxylic groups resulted in derivatives of PGA with increased solubility and processible enough to prepare films (Kubota et al 1993b;Borbély et al 1994;Kishida et al 1998;Muñoz-Guerra et al 1998). By the use of crosslinking reagents [e.g.…”

Effects of Thermoresponsive Coacervation on the Hydrolytic Degradation of Amphipathic Poly(γ‐glutamate)s

“…H. Kubota et al [18] and S. Guerra et al [19][20][21] reported that the esterification of the carboxyl groups of g-PGA improved its solubility in organic solvents and its thermal stability. We previously reported that the g-PGA benzyl ester shows a potential for use as a DDS, [22] and that sulfonated g-PGA shows anti-thrombogenic behavior similar to heparin. [23][24][25] Furthermore, we reported an effective method for producing bionanoparticles derived from phenylalanine ethyl ester pendanted g-PGA.…”