Alendronate-loaded microparticles for improvement of intestinal cellular absorption.
This study examined a novel alendronate formulation that was developed to overcome the shortcomings of alendronate, such as its low bioavailability and gastric adverse effects. Alendronate microparticles were prepared using mucoadhesive polymers such as chitosan for improving the intestinal cellular absorption of alendronate and also using a gastric-resistant polymer such as Eudragit L100-55 for reducing the gastric inflammation of alendronate. Alendronate microparticles including chitosan showed a threefold increase in alendronate uptake (6.92 ± 0.27%) in Caco-2 cells when compared with the uptake of alendronate solution (2.38 ± 0.27%) into Caco-2 cells. Most interestingly, alendronate microparticles including chitosan showed 2.80 x 10⁻⁶ cm/s of an apparent permeability coefficient across Caco-2 cells and caused a significant 42.4% enhancement compared with that of alendronate solution across Caco-2 cells. The morphology of the Caco-2 cells treated with alendronate microparticles including chitosan was similar to that of the untreated cells and alendronate microparticles exhibited a negative effect to propodium iodide with some annexin-V fluorescence isothiocyante positive effect. It was proposed that the novel alendronate microparticles could possess the potential of an increased intestinal absorption and fewer adverse effects of alendronate.
Baek
Jong-Suep
JS
College of Pharmacy and Institute of Drug Research & Development, Chungnam National University, 220 Gungdong, Yuseonggu, Daejeon 305-764, South Korea.
Kwon
Hae-Hyun
HH
Hwang
Ji-Sook
JS
Sung
Ha-Chang
HC
Lee
Jeong-Min
JM
Shin
Sang-Chul
SC
Kim
Young Ran
YR
Cho
Cheong-Weon
CW
D000180:Acrylic Resins / Q000737:chemistry; D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D007408:Intestinal Absorption; D008863:Microspheres; D010539:Permeability; D013270:Stomach / Q000187:drug effects / Q000473:pathology
D000180:Acrylic Resins; D050071:Bone Density Conservation Agents; D004337:Drug Carriers; C446821:Eudragit L100-55; D048271:Chitosan; D019386:Alendronate