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


CONCLUSIONS
Overall, these results suggest that polymeric gemcitabine microparticulate systems could be used as carriers to help oral absorption of gemcitabine.
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Gungdong, Yuseonggu, Daejeon, South Korea.
Ji-Ho
JH
Lim
Sung-Kyun
SK
You
Jong-Suep
JS
Baek
Chan-Ju
CJ
Hwang
Young-Guk
YG
Na
Sang-Chul
SC
Shin
Cheong-Weon
CW
Cho
D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry; D000327:Adsorption; D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D007419:Intestinal Secretions; D008954:Models, Biological; D009077:Mucins / Q000737:chemistry; D050997:Nanomedicine; D013499:Surface Properties; D000093542:Gemcitabine
D000180:Acrylic Resins; D004337:Drug Carriers; C446821:Eudragit L100-55; D009077:Mucins; D003841:Deoxycytidine; D048271:Chitosan; D000093542:Gemcitabine