Publications by authors named "K Shigeno"
The purpose of our research is to develop functional additives that enhance mucosal absorption of biologics, such as peptide/protein and antibody drugs, to provide their non-to-poor invasive dosage forms self-managed by patients. Our previous in vivo and in vitro studies demonstrated that the intranasal absorption of biologics in mice was significantly improved when coadministered with oligoarginines anchored chemically to hyaluronic acid via a glycine spacer, presumably through syndecan-4-mediated macropinocytosis under activation by oligoarginines. The present mouse experiments first revealed that diglycine-L-tetraarginine-linked hyaluronic acid significantly enhanced the intranasal absorption of sulpiride, which is a poor-absorptive organic compound with a low molecular weight.
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- Previous research showed that L-octaarginine linked to hyaluronic acid can improve the absorption of protein drugs under 22 kDa when taken intranasally.
- This study explored its use for larger antibody drugs, showing that the bioavailability of ranibizumab (48 kDa) increased from 0.67% to 6.2% when combined with the hyaluronic acid derivative.
- Results indicated that this absorption enhancement mechanism relies on syndecan-4-induced macropinocytosis, making it effective for various antibody sizes, with no involvement from clathrin or caveolin-1 in the uptake process.
Article Synopsis
- - The study investigates how cell-penetrating peptides attached to polymers can enhance the absorption of biologics through mucosal routes, highlighting past mouse experiments that showed significant improvements in mucosal absorption of protein drugs using hyaluronic acid modified with l-octaarginine.
- - Results revealed that somatropin had a bioavailability of 19% when applied to lung mucosa but only about 1% with nasal administration, which increased to 46% when paired with the absorption enhancer.
- - The effectiveness of the absorption enhancer varied by route; while oral and rectal administration saw improved somatropin absorption, intragastric use did not yield positive results, suggesting the pulmonary route is optimal for administering biologics.
Objective: In the Epley maneuver performed on patients with posterior semicircular canal-benign paroxysmal positional vertigo-canalolithiasis (P-BPPV-Can), an intense downbeat nystagmus and retropulsion rarely appear as soon as they reach the last upright sitting position. It is considered an anterior canal crisis that appears when the otoliths move to the ampullofugal direction in the anterior semicircular canal by changing head and body positions from the healthy-ear-down 135° head position (the third head position) to the upright sitting position (the fourth head position). This study aimed to determine the prevention of this anterior canal crisis.
View Article and Find Full Text PDFObjective: Otolithic dysfunction is investigated in cases of direction-changing horizontal positional nystagmus (DCHPN) due to peripheral vestibular disorders.
Methods: The static-subjective visual vertical (S-SVV) was conducted in DCHPN cases within 48 h after onset.
Results: The absolute values of S-SVV deviations of patients with Light cupula and lateral canal-benign paroxysmal positional vertigo-cupulolithiasis (L-BPPV-Cup) were significantly different from those of healthy subjects (p < 0.