Introduction Alendronate, which is used clinically to treat oste- oporosis (Tenenbaum et al., 2002), shows less than 1% bioavailability in humans due to the low absorption in gastrointestinal tract (Porras, Holland & Gertz, 1999). In addition, it was known that alendronate interacts with various foods, which further reduces its oral bio- availability approximately 10-fold (Kimmel, 2007), and induces esophagitis (Lufkin et al., 1994; Maconi & Porro, 1995; Graham, 1998; Graham & Malaty, 1999) that may be based on the inhibition of Farnesyl diphosphate synthase (Graham, 2002). erefore, some researchers have published to improve the oral bioavailability of alendronate. Representatively, alendronate was for- mulated to a microemulsion with stability for improv- ing its oral absorption (Karamustafa & çelebi, 2008), and mucoadhesive poly(vinylamine) conjugates with a peptapeptide sequences Suc-Gly-Gly-Phe-Ala-Pro of alendronate were synthesized resulting in a 2.5-fold increase in its oral absorption (Sakuma et al., 2007). Also, a complex between vitamin D and alendronate was used for clinical use (Anić & Grazio, 2006; Ringe et al., 2007). Journal of Drug Targeting, 2011; 19(1): 37–48 * ese authors contributed equally to this work. Address for Correspondence: Cheong-Weon Cho, College of Pharmacy and Institute of Drug Research & Development, Chungnam National University, 220 Gungdong, Yuseonggu, Daejeon 305-764, South Korea. E-mail: chocw@cnu.ac.kr ORIGINAL ARTICLE Alendronate-loaded microparticles for improvement of intestinal cellular absorption Jong-Suep Baek 1,* , Hae-Hyun Kwon 1,* , Ji-Sook Hwang 1 , Ha-Chang Sung 2 , Jeong-Min Lee 2 , Sang-Chul Shin 3 , Young Ran Kim 4 , and Cheong-Weon Cho 1 1 College of Pharmacy and Institute of Drug Research & Development, Chungnam National University, 220 Gungdong, Yuseonggu, Daejeon 305-764, South Korea, 2 Life Science R&D Center, Sinil Pharmaceutical Co., San 5-1, Bonpyungri, Angsungmyun, Chungjusi, Chungcheongbukdo 380-862, South Korea, 3 College of Pharmacy, Chonnam National University, 300 Yongbongdong, Buggu, Gwangju 500-757, South Korea, and 4 Dongshin University, 252 Daehodong, Naju, Jeonnam 520-714, South Korea Abstract 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 × 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 fluores- cence 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. Keywords: Alendronate; microparticles; mucoadhesive; enteric-coating; polymer; cellular uptake; transport; Caco-2 cell; side effects; absorption; in vitro release (Received 27 September 2009; revised 01 February 2010; accepted 01 February 2010) ISSN 1061-186X print/ISSN 1029-2330 online © 2011 Informa UK, Ltd. DOI: 10.3109/10611861003667599 http://www.informahealthcare.com/drt