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Anti-VEGF PolysiRNA Polyplex for the Treatment of Choroidal Neovascularization
Lee, Jihwang,Ryoo, Na-kyung,Han, Hyounkoo,Hong, Hye Kyoung,Park, Ji Yeon,Park, Sang Jun,Kim, Yong-Kyu,Sim, Changbeom,Kim, Kwangmeyung,Woo, Se Joon,Park, Kyu Hyung,Kim, Hyuncheol American Chemical Society 2016 MOLECULAR PHARMACEUTICS Vol.13 No.6
<P>Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration (AMD). Present ocular siRNA delivery technology is limited due to poor delivery through the retina to the choroid, where CNV originates. Our goal was to develop an optimized nanosized polyRNAi-based therapeutic delivery system to the subretinal space. We developed it by siRNA multimerization (polysiRNA) followed by coating with branched polyethylenimine and hyaluronic acid, and then evaluated its efficacy in vitro and in vivo. The polysiRNA polyplex showed a narrow size distribution (260.7 +/- 43.27 nm) and negative charge (-4.98 +/- 0.47 mV) owing to the hyaluronic acid outer layer. In vitro uptake of the polysiRNA polyplex by human ARPE cells was discovered, and the direct inhibition of VEGF mRNA translation was confirmed in B16F10 cells. The intravitreally administered polysiRNA polyplex overcame both the vitreous and retina barriers in vivo and reached the subretinal space efficiently. Intravitreal injection of the polysiRNA polyplex was not toxic to the retina in histopathology. Furthermore, intravitreal injections of the polysiRNA polyplex at both 1 and 7 days after laser photocoagulation inhibited laser-induced choroidal neovascularization, compared to that of the control (p < 0.05). These results suggest that anti-VEGF polysiRNA polyplexes show great potential in delivering multimeric RNAi-based therapeutics to treat retinal or choroidal disorders.</P>
Ryoo, Na-Kyung,Lee, Jihwang,Lee, Hyunjoo,Hong, Hye Kyoung,Kim, Hyejin,Lee, Jong Bum,Woo, Se Joon,Park, Kyu Hyung,Kim, Hyuncheol Royal Society of Chemistry 2017 Nanoscale Vol.9 No.40
<P>Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries and is characterized by the development of choroidal neovascularization (CNV). Therapies for AMD have focused on suppressing angiogenic factors, such as vascular endothelial growth factor (VEGF), mainly<I>via</I>conventional anti-VEGF antibody agents. However, additional efforts have been made to develop effective small-interfering RNA (siRNA)-based intracellular therapeutic agents. In this study, we have manufactured a novel siRNA-based anti-VEGF nanoball (siVEGF NB). The siVEGF NB was composed of a siRNA hydrogel with a core of anti-VEGF sequence siRNA coated with branched PEI (bPEI) and hyaluronic acid (HA) in order by applying an electrical force. The novel siVEGF NBs, which were employed in a laser-induced CNV mouse model, were optimized as a retinal and choroidal delivery system through the vitreous humor to the sub-retinal space<I>via</I>CD44 receptor endocytosis on the inner limiting membrane, and showed therapeutic effects<I>via</I>pathways bypassing the TLR3-induced siRNA-class effect. The therapeutic effects of siVEGF NBs lasted for 2 weeks after intravitreal injection showing high targeting efficiency to the sub-retinal space. Thus, the newly developed siVEGF NB may have great potential for the delivery of RNAi-based therapeutics for ocular diseases, including AMD.</P>
회전구동 정전형 마이크로 액추에이터를 이용한 고트랙밀도 HDD 용 이단 구동 시스템
전종업(Jong Up Jeon),정성환(Sunghwan Jung),최재준(Jae-Joon Choi),박지황(Jihwang Park),이창호(Chang-Ho Lee),김철순(Cheol-Soon Kim),민동기(Dong-Ki Min),김영훈(Young-Hoon Kim),이승희(Seung-Hi Lee) Korean Society for Precision Engineering 2005 한국정밀공학회지 Vol.22 No.10
This paper presents the design, fabrication, and testing results of a dual stage actuator system for a fine positioning of magnetic heads in magnetic disk drives. A novel rotary microactuator which is electrostatically driven and utilized as a secondary actuator was designed. The stator and rotor electrodes in the microactuator was revised to have the optimal shapes and hence produces much higher rotational torque compared with the conventional comb-shape electrodes. The microactuators were successfully fabricated using SoG(silicon on glass) processing technology, which is known as being cost-effective. The fabricated microactuator has the structural thickness of 45㎛ with the gap width of approximately 3㎛. The dynamic characteristic of microactuatorlslider assembly was investigated, and its natural frequency and DC gain were measured to be 304㎑ and 32㎛/V, respectively. The microactuatorlslider assembly was integrated into a HDD model V10 of Samsung Electronics Co. and a dual servo algorithm was tested to explore the tracking performance of dual stage actuator system where the LDV signals instead of magnetic head signals were used. Experimental res ults indicate that this system achieves the tracking accuracy of 30㎛. This value corresponds to a track density of 85,000 track per inch(TPI), which is about 3 times greater than that of current hard disk drives.