Optimization of 5-fluorouracil solid-lipid nanoparticles: A preliminary study to treat colon cancer

Solid lipid nanoparticle (SLNs) formulae were utilized for the release of 5-fluorouracil (5-FU) inside the colonic medium for local treatment of colon cancer. SL Ns were prepared by double emulsion-solvent evaporation technique (w/o/w) using triglyceride esters, Dynasan™ 114 or Dynasan™ 118 along with soyalecithin as the lipid parts. Different formulation parameters; including type of Dynasan, soyalicithin: Dynasan ratio, drug: total lipid ratio, and polyvinyl alcohol (PVA) concentration were studied with respect to particle size and drug entrapment efficiency. Results showed that formula 8 (F8) with composition of 20% 5 -FU, 27% Dynasan™ 114, and 53% soyalithicin and F14 (20% 5-FU, 27% Dynasan™ 118, and 53% soyalithicin), which were stabilized by 0. 5% PVA, as well as F10 with similar composition as F8 but stabilized by 2% PVA were considered the optimum formulae as they combined small particle sizes and relatively high encapsulation efficiencies. F8 had a particle size of 402.5 nm ± 34.5 with a polydispersity value of 0.005 and an enca psulati on efficiency of 51%, F10 had a 617. 3 nm ± 54. 3 particle size with 0.005 polydispersity value and 49.1% encapsulation efficiency, whereas formula F14 showed a particle size of 343 nm ± 29 with 0.005 polydispersity, and an encapsulation efficiency of 59. 09%. DS C and FTIR results suggest ed the existence of t he lipids in the solid crystalline state. Incomplete biphasic prolonged release profile of the drug from The three formulae was observed in phosphate buffer p H 6. 8 as well as simulated colonic medium containing rat caecal contents. A burst release with magnitudes of 26%, 32% and 28.8% cumulative drug released were noticed in the first hour samples incubated in phosphate buffer p H 6. 8 for both F8, F10 and F14, respectively, followed by a slow release profile reaching 50%, 46.3% and 52% after 48 hours.