Mucoadhesive, nanostructured microparticles for their prolonged retention in gastrointestinal tract

Abstract

Event Abstract Back to Event Mucoadhesive, nanostructured microparticles for their prolonged retention in gastrointestinal tract Chun Gwon Park1, Beom Kang Huh2, Se Na Kim2, Seung Ho Lee2, Min Park2, Hye Rim Hong2, Ka Ryeong Kim2, Hyein Won2 and Young Bin Choy1, 2, 3 1 Seoul National University, Institute of Medical & Biological Engineering, Korea 2 Seoul National University, Interdisciplinary Program for Bioengineering, Korea 3 Seoul National University, Department of Biomedical Engineering, Korea Introduction: Oral drug of poor bioavailability often needs multiple daily administrations to maintain a therapeutically effective level of systemic drug concentration, which is limited in an inconvenient regimen of drug therapy. In this sense, the carriers, which could stay in the gastrointestinal (GI) tract and also release drug in a sustained manner, would be useful. For this, we propose mucoadhesive, nanostructured microparticles as a potential oral-drug carrier in this work. Those functional microparticles herein possessed a high specific surface area originated from their nanostructure, hence improved mucoadhesion through a gastrointestinal (GI) tract [1]. We examined the in vivo retention time of the microparticles in the GI tract after their oral administration in living rats in this study. Methods: Four different types of the microparticles were prepared to examine the effect of particle morphology (i.e., spherical or nanostructured) and mucoadhesiveness on their residence time in GI tract: spherical microparticles (MS) of PLGA only (PLGA MS), MS of PLGA and PEG (PLGA/PEG MS), nanostructured microparticles (NM) of PLGA only (PLGA NM) and NM of PLGA and PEG (PLGA/PEG NM) [1]. The microparticles were composed mainly of PLGA, where PEG was used as additive to give a mucoadhesion property. The MS was prepared by the conventional emulsion method. The NM was prepared by freeze-milling the nanofibrous sheets prepared via electrospinning. All microparticles were labeled with near-infrared fluorescent dye, 3,3′-Diethylthiatricarbocyanine iodide (DTTCI) and orally administered to living rat to monitor their retention property in the GI tract (IVIS (Lumina II); excitation and emission wavelengths of 745 and 840 nm, respectively). The suspensions containing the DTTCI only was also evaluated for comparison. Results and Conclusion: The MS prepared by the emulsion method exhibited a spherical shape with a smooth surface (Fig. 1(a-b)). The NM showed the morphology with randomly entangled nanofibers to give a rough surface (Fig. 1(c-d)). The presence of PEG in microparticles did not seem to influence their own purposed surface morphology (Fig. 1) Figure 1(e) shows the in vivo fluorescence images of the whole rats at scheduled times after oral administration of the microparticle formulations. For all control groups (i.e., the dye suspension, PLGA MS, PLGA/PEG MS and PLGA NM groups), fluorescence signal was observed through the GI tract for up to 12 h, which, however, became not detectable afterwards. On the other hand, the PLGA/PEG NM showed the best retention in GI tract as their fluorescence signal was detectable until 36 h. This could be ascribed to the fact that mucoadhesiveness was synergistically improved by the enlarged specific surface area originated from the nanostructure of the PLGA/PEG NM. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF- 2013R1A1A2A10011055); This research was supported by BK21 Plus Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant numbers 22A20130011025)