Polymer Drugs and Polymeric Drugs IX. Synthesis and 5-Fluorouracil Release Profiles of Biodegradable Polymeric Prodrugs γ-Poly(α-Hydroxymethyl-5-Fluorouracil-Glutamate)

Abstract

A conjugate of poly(y-glutamic acid)(y-PGA) with 5-fluorouracil (5-FU) (y-poly(a-hydroxymethyl-5-fluorouracil-glutamate)), y-PFUG, was prepared as a polymeric prodrug matrix. The release of 5-FU and the degradation behavior of y-PFUG, which is soluble in polar organic solvents were studied. y-PFUG films were prepared by casting from DMF. The y-PFUG matrix degraded in 7 days and incorporated 5-FU was released in 3 days. 5-FU release was accelerated by mixing free 5-FU into y-PFUG. Here, y-PFUG functioned as a hydrophobic degradable matrix. Analogous with y-PFUG, y-PGA conjugated with a drug may be useful as a biodegradable polymeric prodrug.

Tunable drug release profiles from salicylate-based poly(anhydride-ester) matrices using small molecule admixtures

“…29 As these channeling agents are solubilized, pores are created in the disc surface, increasing water penetration and subsequent polymer degradation. 30 This effect has been observed using salt leaching techniques, 31 as well as admixing molecules such as drugs 15,32 or inert polymer precursors into the polymer matrix. 33,34 For example, PLGA monomers (10% w/w) acting as channeling agents in drug-loaded PLGA discs resulted in the absence of a lag period in drug release.…”