Publications by authors named "Tatsunori Hirotsu"

Article Synopsis
  • Bietti's crystalline dystrophy (BCD) is a genetic eye condition caused by mutations in the CYP4V2 gene, leading to cholesterol buildup and crystal deposits in the retina.
  • Hydroxypropyl-β-cyclodextrin (HP-β-CyD) can help manage BCD by reducing cell damage but has low retention in the eye, which this study aims to address.
  • The research shows that using xanthan gum as a carrier for HP-β-CyD results in better sustained release and reduced toxicity compared to other agents, making it a promising option for eye drops in treating BCD.
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Raltegravir (RAL), a human immunodeficiency virus (HIV)-1 integrase inhibitor, has been administered as part of antiretroviral therapy. Studies in patients with HIV-1 have shown high variability in the pharmacokinetics of RAL, and in healthy volunteers, coadministration of proton-pump inhibitors has been shown to increase the plasma RAL concentrations. Here, we found that RAL containing a 1,3,4-oxadiazole ring is converted to a hydrolysis product (H-RAL) with a cleaved 1,3,4-oxadiazole ring at pH 1.

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Pancreatic cancer is one of the most difficult cancers to treat largely because of the inability of anticancer drugs to penetrate into the cancer tissue as the result of the dense extracellular matrix (ECM). On the other hand, bromelain is known to degrade the ECM in cancerous tissue. However, the half-life of bromelain in blood is short, leading to its low accumulation in tissues.

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Sustained and controllable release of insulin is strongly required to achieve the ideal treatment of diabetes. We previously developed "self-assembly PEGylation retaining activity (SPRA) technology" via a host-guest interaction between PEGylated β-cyclodextrin and adamantane-appended insulin, and resulting PEGylated insulin was termed SPRA-insulin. So far, we also demonstrated that covalently PEGylated insulin forms polypseudorotaxanes (PPRXs) with cyclodextrins (PPRX technology).

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Antibodies often have poor physicochemical stability during storage and transport, which is a serious drawback for the development of antibody-based drugs. In this study, we prepared polypseudorotaxane (PPRX) hydrogels consisting of cyclodextrins (CyDs) and polyethylene glycol, and evaluated them as stabilizers for commercially available antibody-based drugs. α-CyD and γ-CyD formed PPRX hydrogels with polyethylene glycol (molecular weight 20,000 Da) in the presence of antibody-based drugs such as omalizumab, palivizumab, panitumumab, and ranibizumab.

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Polyethylene glycol (PEG) modification (PEGylation) is one of the best approaches to improve the stabilities and blood half-lives of protein drugs; however, PEGylation dramatically reduces the bioactivities of protein drugs. Here, we present "self-assembly PEGylation retaining activity" (SPRA) technology via a host-guest interaction between PEGylated β-cyclodextrin (PEG-β-CyD) and adamantane-appended (Ad) proteins. PEG-β-CyD formed stable complexes with Ad-insulin and Ad-lysozyme to yield SPRA-insulin and SPRA-lysozyme, respectively.

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To achieve the potent therapeutic effects of human immunoglobulin G (IgG), highly concentrated formulations are required. However, the stabilization for highly concentrated human IgG is laborious work. In the present study, to investigate the potentials of polypseudorotaxane (PPRX) hydrogels consisting of polyethylene glycol (PEG) and α- or γ-cyclodextrin (α- or γ-CyD) as pharmaceutical materials for highly concentrated human IgG, we designed the PPRX hydrogels including human IgG and evaluated their pharmaceutical properties.

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