A Novel Method to Prepare 5-Fluorouracil, an Anti-cancer Drug, Loaded Microspheres from Poly(N-vinyl caprolactam-co-acrylamide) and Controlled Release Studies

Abstract

Poly(N-vinyl caprolactam-co-acrylamide) co-polymers cross-linked with N,N -methylene bisacrylamide loaded with 5-fluorouracil (5-FU) have been investigated for controlled release of 5-FU, an anticancer drug. Microspheres of poly(N-vinyl caprolactam-co-acrylamide) co-polymers cross-linked with N,N -methylene bisacrylamide have been prepared by free radical emulsion polymerization using varying amounts of acrylamide (AAm), N-vinyl caprolactam (VCL) and N,N -methylene bisacrylamide (NNMBA). Particles were produced in the size range of 16-34 µm and 5-FU was encapsulated into these microspheres. The in situ polymerization and release kinetics of drug-loaded microspheres have been investigated in phosphate buffer solution (pH 7.4) at 25 and 37 • C. Scanning electron microscopy (SEM) was used to study the surface morphology of the microspheres. In vitro release data have been affected by varying the co-polymer composition, amount of cross-linking agent and amount of drug loading in the microspheres. Microspheres with different co-polymer compositions were obtained in yields up to 80-85% with encapsulation efficiencies ranging from 69 to 79%. SEM suggested a spherical nature of particles with somewhat rough surfaces. In vitro drug release data indicated that particle size and release kinetics have been influenced by co-polymer composition, amount of cross-linking agent and amount of 5-FU loaded in the microspheres.

Use of Zeolite ZSM-5 for Loading and Release of 5-Fluorouracil

“…As a derivative of uracil, it rapidly enters the cell where it is converted into active metabolites that disrupt RNA synthesis and acts as inhibitor of thymidylate synthase, a nucleotide synthesis enzyme [4]. However, the oral use of 5-FU exhibits a short plasma half-life (30 min) as a result of its rapid enzymatic metabolism [5], which demands continuous high doses thus leading to high toxicity, incomplete and nonuniform oral distribution, drug resistance by tumor cells, and nonselective action against normal cells [6,7]. Different delivery systems have been used to ensure prolonged and sustained release of 5-FU.…”

A Study of 5-Fluorouracil Desorption from Mesoporous Silica by RP-UHPLC

“…5-Fluorouracil (5-FU) is a water-soluble pyrimidine analogue (Figure 1), used in cancer treatment that has been particularly effective in the treatment of colorectal cancer [22,23], stomach, breast, and head and neck cancers [24,25]. Despite its water solubility, this antitumor agent suffers from several drawbacks: the oral use of 5-FU exhibits a short plasma half-life (30 min) as a result of its rapid enzymatic metabolism [26], which demands continuous high doses that simultaneously lead to high toxicity, incomplete and non-uniform oral absorption, the development of drug resistance by tumor cells, and nonselective action against normal cells [27,28].…”

Effect of Basic Factors of Preparation on Characteristics, Hydrolytic Degradation, and Drug Release From Poly(ester-anhydride) Microspheres

“…These spherical shaped devices in the size range of 1 mm to 2 mm [9][10][11] are used to entrap small molecules [2,[12][13][14][15][16][17], large proteins [18][19][20][21], and even DNA [22][23]. Polyesters and polyanhydrides are two families of polymers that are strong candidates for biomedical applications because of their biocompatibility and bioresorbability of degradation products [2,3,[24][25][26][27][28].…”