Preparation and evaluation of polymeric microparticulates for improving cellular uptake of gemcitabine

Abstract

Background: Gemcitabine must be administered at high doses to elicit the required therapeutic response because of its very short plasma half-life due to rapid metabolism. These high doses can have severe adverse effects. Methods: In this study, polymeric microparticulate systems of gemcitabine were prepared using chitosan as a mucoadhesive polymer and Eudragit L100-55 as an enteric copolymer. The physicochemical and biopharmaceutical properties of the resulting systems were then evaluated. Results: There was no endothermic peak for gemcitabine in any of the polymeric gemcitabine microparticulate systems, suggesting that gemcitabine was bound to chitosan and Eudragit L100-55 and its crystallinity was changed into an amorphous form. The polymeric gemcitabine microparticulate system showed more than 80% release of gemcitabine in 30 minutes in simulated intestinal fluid. When mucin particles were incubated with gemcitabine polymeric microparticulates, the zeta potential of the mucin particles was increased to 1.57 mV, indicating that the polymeric gemcitabine microparticulates were attached to the mucin particles. Furthermore, the F53 polymeric gemcitabine microparticulates having 150 mg of chitosan showed a 3.8-fold increased uptake of gemcitabine into Caco-2 cells over 72 hours compared with gemcitabine solution alone. Conclusion: Overall, these results suggest that polymeric gemcitabine microparticulate systems could be used as carriers to help oral absorption of gemcitabine.

Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta

“…Changes in size and zeta potential of GSNO-NPs in contact with a mucin dispersion were examined. 36 After centrifugation free GSNO respectively, was decomposed (Figure 2, A, B).…”

Permeability of Gemcitabine and PBPK Modeling to Assess Oral Administration

“…The successful formation of a monolayer of Caco-2 cells was verified by observation under an optical microscope, with no detection of anomalies or areas without cells, a reliable indicator for proceeding with the permeability study. The integrity of the cells was not compromised by the concentration of gemcitabine used in the permeability assay (60 µM), since the IC50 of this drug is far greater (approximately 50 mM, as determined experimentally via MTT assay and previously reported by Lim et al [18]). Results are presented in Figure 2 as a percentage of recovery from the basolateral compartment.…”