Development of drug treatment using sugar-chain modified liposome for the macaque monkey model of retinal vein occlusion

• Project/Area Number: 18K09443
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: SAISHIN YOSHITSUGU 滋賀医科大学, 医学部, 准教授 (30379193)
• Co-Investigator(Kenkyū-buntansha): 一山 悠介 滋賀医科大学, 医学部, 助教 (10749021)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 網膜静脈閉塞症 / たんぱく質 / リポソーム / カニクイザル

Outline of Final Research Achievements

Fluorescently labeled liposomes were prepared for the purpose of drug treatment with liposomes. A variety of proteins were encapsulated. The intensity-average diameter of the liposomal nanoparticles was approximately 100 nm. Liposomes encapsulated with human immunoglobulin were prepared and characterized. The size of liposomes remained 89nm until 13 months at 4 degree. The leakage amount at 60 days was approximately 3.436μg. The liposomes can lead to the slow and controlled release of drug. These results suggest that liposomes encapsulated with drug may be feasible for antibody treatment of retinal vein occlusion.

Academic Significance and Societal Importance of the Research Achievements

リポソームは生体膜に大量に存在するリン脂質、コレステロールなどを主成分とする人工の脂質二重膜でできた粒子径100nmの微細なカプセルである。封入する薬剤については、直接化学修飾する必要がないので、実用化への過程が短くてすむ。抗体や糖脂質などをリポソーム表面に組み込むことにより、特定の組織、細胞に対して標的指向性をもつリポソームを作製できる。また作製した薬剤内包リポソームに薬剤徐放効果があることがわかった。この標的指向性薬剤内包リポソームを用いることで、網膜静脈閉塞症に対する抗VEGF阻害薬の硝子体内投与に代わる新たな創薬コンセプトの確立への手掛かりとなった。

Research Products

• [Journal Article] The Correlation between Aqueous Vascular Endothelial Growth Factor Level and Clinical Activity in Neovascular Age-Related Macular Degeneration. (2021)
  • Author(s): Ichiyama Y, Sawada T, Sawada O, Ito Y, Kakinoki M, Obata S, Saishin Y, Ohji M
  • Journal Title: Retina Volume: 41 Issue: 1 Pages: 111-117
  • DOI: 10.1097/iae.0000000000002790
  • Peer Reviewed
• [Journal Article] The systemic antiangiogenic effect of intravitreal aflibercept injection in a mouse model of retinopathy of prematurity. (2021)
  • Author(s): Ichiyama Y, Obata S, Saishin Y, Sawada O, Kakinoki M, Sawada T, Kubota Y, Ohji M
  • Journal Title: FASEB J Volume: 35 Issue: 3
  • DOI: 10.1096/fj.202002414r
  • Peer Reviewed
• [Journal Article] Evaluation of acquired color vision deficiency in retinal vein occlusion using the Rabin cone contrast test. (2021)
  • Author(s): Matsumoto R, Saishin Y, Ohji M
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. Volume: Online ahead of print. Issue: 10 Pages: 2961-2966
  • DOI: 10.1007/s00417-021-05171-7
  • Peer Reviewed
• [Journal Article] Vogt-Koyanagi-Harada Disease-Like Uveitis during Nivolumab (Anti-PD-1 Antibody) Treatment for Metastatic Cutaneous Malignant Melanoma. (2019)
  • Author(s): Obata S, Saishin Y, Teramura K, Ohji M
  • Journal Title: Case Rep Ophthalmol. Volume: 10 Issue: 1 Pages: 67-74
  • DOI: 10.1159/000496682
  • Peer Reviewed
• [Journal Article] Comparison of Surgical Outcomes Between Two Types of Lamellar Macular Holes. (2019)
  • Author(s): Obata S, Ichiyama Y, Kakinoki M, Sawada O, Saishin Y, Ohji M
  • Journal Title: Clin Ophthalmol. Volume: 13 Pages: 2541-2546
  • DOI: 10.2147/opth.s231363
  • NAID: 120006777344
  • Peer Reviewed
• [Journal Article] Comparison between wide-angle OCT angiography and ultra-wide field fluorescein angiography for detecting non-perfusion areas and retinal neovascularization in eyes with diabetic retinopathy. (2018)
  • Author(s): Sawada O, Ichiyama Y, Obata S, Ito Y, Kakinoki M, Sawada T, Saishin Y, Ohji M
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. Volume: 256 Issue: 7 Pages: 1275-1280
  • DOI: 10.1007/s00417-018-3992-y
  • Peer Reviewed
• [Journal Article] Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration. (2018)
  • Author(s): Sawada T, Wang X, Sawada O, Saishin Y, Ohji M
  • Journal Title: Clin Exp Ophthalmol. Volume: 46 Issue: 1 Pages: 46-53
  • DOI: 10.1111/ceo.13002
  • Peer Reviewed
• [Presentation] Comparison of imaging area between CLARUS and Optos (2019)
  • Author(s): Okamoto R, Sawada O, Ichiyama Y, Obata S, Kakinoki M, Sawada T, Saishin Y, Ohji M
  • Organizer: The Association for Research in Vision and Ophthalmology, Annual Meeting. (Vancouver, Canada, April 28 - May 2, 2019)
• [Presentation] Color abnormality measured with the Rabin cone contrast test in central serous chorioretinopathy. (2019)
  • Author(s): Murotani S, Kakinoki M, Ichiyama Y, Obata S, Iwasa M, Sawada O, Sawada T, Saishin Y, Ohji M
  • Organizer: The Association for Research in Vision and Ophthalmology, Annual Meeting. (Vancouver, Canada, April 28 - May 2, 2019)
• [Presentation] Investigation of postoperative refractive error of intraocular lens suturing and intrascreral fixation. (2019)
  • Author(s): Kakinoki M, Sawada O, Saishin Y, Ichiyama Y, Obata S, Ohji M
  • Organizer: The Association for Research in Vision and Ophthalmology, Annual Meeting. (Vancouver, Canada, April 28 - May 2, 2019)
• [Presentation] Combination of topical bromfenac and ranibizumab therapy for BRVO (2018)
  • Author(s): Yoshitsugu Saishin
  • Organizer: The 57th Annual Meeting of Japanese Retina and Vitreous Society
• [Presentation] Anti-VEGF therapy for retinal vein occlusion (2018)
  • Author(s): Yoshitsugu Saishin
  • Organizer: The 123rd Annual Meeting of the Japanese Ophthalmological Society