Membrane-encased polymer millirods for sustained release of 5-fluorouracil.
This article describes the design and development of a novel membrane-encased polymer millirod for the sustained release of an anticancer drug, 5-fluorouracil (5-FU). The millirod consists of two functional compartments: (1) an inner 5-FU-loaded monolithic millirod as the drug depot, and (2) an outer NaCl-impregnated polymer membrane to control the release rate of 5-FU. The inner millirod is fabricated by a compression-heat molding procedure to permit the entrapment of 5-FU particles in the poly(D,L-lactide-co-glycolide) (PLGA) matrix. The drug loading density is controlled at 30 w/w% to achieve a burst release of 5-FU (>90% of the drug are released within 48 h) from the monolithic millirod. The NaCl-impregnated PLGA membrane is generated by solvent casting and is then wrapped over the monolithic millirod to produce the membrane-encased millirod. Scanning electron microscopy shows that dissolution of NaCl particles produces a semipermeable polymer membrane to provide a sustained release of 5-FU. The membrane thickness and the density of NaCl particles inside the membrane are useful parameters to control the release kinetics of 5-FU. Under the experimental conditions in this study, sustained release of 5-FU [rates between 0.1 and 0.4 mg/(day. cm of millirod)] is achieved for 2 to 5 weeks in phosphate-buffered saline (pH 7.4) at 37 degrees C. Results from this study demonstrate that membrane-encased polymer millirods provide controllable sustained release kinetics for applications in intratumoral drug delivery.
Qian
Feng
F
Cancer-Targeted Drug Delivery Laboratory, Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
Nasongkla
Norased
N
Gao
Jinming
J
D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000493:pharmacokinetics*; D007700:Kinetics; D019344:Lactic Acid; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012965:Sodium Chloride; D013997:Time Factors
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008567:Membranes, Artificial; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012965:Sodium Chloride; D005472:Fluorouracil