| 박천권(1), 김영국(2,3), 김미정(2,3), 박민(1), 김명훈(1), 이승호(1), 최성윤(1), 정유정(4), 정영은(4), 박기호(2,3), 최영빈(1,4,5) |
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목적 : Low drug bioavailability of eye drops is often considered problematic due to rapid preocular clearance. To resolve this, we fabricated the nanostructured microparticles (NM), composed of poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) as wall material and mucoadhesion promoter, respectively, and used them as delivery carrier of a glaucoma drug, brimonidine (BRT). The NM herein can adhere to the mucous layer on the eye surface for a prolonged time, releasing the drug in a sustained manner, thereby higher bioavailability of BRT.
방법 : Conventional microspheres (MS) were fabricated with the emulsion method and the NM were prepared by freeze-milling the nanofibrous sheets. The MS and NM were each prepared with two distinct compositions, PLGA only and a blend of PLGA and PEG to give four different types of microparticles: PLGA MS, PLGA/PEG MS, PLGA NM and PLGA/PEG NM, which were then formulated in a tablet of polyvinyl alcohol (PVA). For the in vivo evaluation, the intraocular pressure (IOP) of the rabbit eyes was measured after administration of each of the four different microparticle formulations.
결과 : The NM were seen to be composed of randomly organized nanofibers to give a rough surface, resulting in an increase in specific surface area and thus, adhering better to the eye surface when incorporated with a mucoadhesive material, PEG. Thus, the best IOP-lowering effect was observed with the PLGA/PEG NM, which was prolonged for up to 13 h. On the other hand, for the other types of the microparticles and Alphagan P, the periods of lowered IOP were 9 – 10 h and 6 h, respectively.
결론 : In this work, we suggest nanostructured, mucoadhesive microparticles as a potential system for topical drug delivery to the eye. The mucoadhesion property of NM can be enhanced with their large surface area, thereby better adherence to the preocular surface. In this way, the NM can deliver the drug in a sustained manner to improve drug bioavailability. In this work, when delivered with the PLGA/PEG NM, the IOP-lowering effect of BRT improved more than twice, as compared with Alphagan-P, the medication already approved in clinical use.
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