No abstract

PurposeWe developed polycaprolactone (PCL) implants that achieve zero-order release of a proprietary ocular hypotensive agent (DE-117) over 6 months.MethodsThe release rates of DE-117–loaded PCL devices were tuned based on an established predictive model and confirmed by in vitro release studies. Devices containing DE-117 and empty devices were implanted intracamerally in normotensive rabbits for up to 8 weeks' duration. Devices were retrieved after rabbits were euthanized and evaluated for tissue adherence. The drug remaining in each device was analyzed by high performance liquid chromatography. Drug distribution in ocular tissues was measured by liquid chromatography coupled with a tandem mass spectrometry (LC/MS/MS).ResultsIn vitro release of DE-117 showed zero-order release with a release rate of 0.5 μg/day over 6 months. Implantation in rabbit eyes demonstrated that the devices were well tolerated in the intracameral space. Quantification of DE-117 and hDE-117 (the hydrolyzed active form of DE-117) in ocular tissues (cornea, iris-ciliary body, aqueous humor, and vitreous humor) indicated sustained release of DE-117 and its conversion to hDE-117 when released from the device. Analysis of drug remaining in the device found that concentration of hDE-117 was below the limit of detection, indicating the encapsulated drug was protected from hydrolysis in the device.ConclusionsProof-of-concept PCL drug delivery devices containing DE-117 show promise as a long-term glaucoma treatment based on their zero-order drug release profile in vitro, biocompatibility in vivo, and effective distribution of released drug in relevant ocular tissues.

Both CBF and CVR decrease with the development of NPH, suggesting that hemodynamic ischemia may be responsible for manifestation of the symptoms. Impaired CVR and reduced CBF with the development of symptoms can be proposed as diagnostic criteria for idiopathic NPH.

GKS for brain stem metastases using a marginal dose of 15 Gy or less is effective and relatively safe. Accurate targeting of the tumour and safe dose planning are essential to obtain satisfactory results with GKS for brain stem metastases.

Long-term treatment of glaucoma, a major leading cause of blindness, is challenging due to poor patient compliance. Therefore, a drug delivery device that can achieve drug release over several months can be highly beneficial for glaucoma management. Here, we evaluate the long-term pharmacokinetics and therapeutic efficacy of polycaprolactone intracameral drug delivery devices in rabbit eyes. Our study showed that a single drug delivery device loaded with a proprietary hypotensive agent, DE-117, reduced intraocular pressure in normotensive rabbits significantly for 23weeks. In addition, we demonstrated that concentration of DE-117 and its hydrolyzed active form (hDE-117) was maintained in the aqueous humor and the target tissue (iris-ciliary body) up to 24weeks. Our proof-of-concept glaucoma implant shows potential as a long-term treatment that circumvents patient compliance barriers compared to current treatment via eye drops.

The predictors of restenosis after endovascular therapy (EVT) with paclitaxel drug-coated balloons (DCBs) have not been clearly established. The present study aimed to investigate the association of post-procedural dissection, as evaluated using intravascular ultrasound (IVUS), with the risk of restenosis following femoropopliteal EVT with paclitaxel DCBs. Methods:In the present single-center retrospective study, 60 de novo femoropopliteal lesions (44 patients) that underwent EVT with DCBs, without bail-out stenting, were enrolled. The primary outcome was 1-year primary patency. Risk factors for restenosis were evaluated using a Cox proportional hazards regression model and random survival forest analysis. Results:The 1-year primary patency rate was 57.2% [95% confidence interval, 45%-72%]. IVUS-evaluated post-procedural dissection was significantly associated with the risk of restenosis (P 0.002), with the best cutoff point of 64º [range, 39º-83º]. The random survival forest analysis showed that the variable importance measure of IVUS-evaluated dissection was significantly lower than that of the reference vessel diameter (P 0.001), not different from that of the lesion length (P 0.41), and significantly higher than that of any other clinical feature (all P 0.05). Conclusion: IVUS-evaluated post-procedural dissection was associated with 1-year restenosis following femoropopliteal EVT with DCB.percutaneous transluminal angioplasty (PTA) using uncoated balloons [5][6][7] . Severe dissection evaluated using angiography has been reported as an important risk factor for restenosis following PTA with uncoated balloons 8) ; however, predictors of restenosis have not been clearly established.Intravascular ultrasound (IVUS) imaging provides detailed, high-quality, real-time images.

Optimization of benzalkonium chloride (alkyl dimethylbenzylammonium chloride: BAK) concentration as preservative in 0.0015％ ta‰uprost ophthalmic solution (Tapros0.0015％ ophthalmic solution), an anti-glaucoma medicine, was examined from the points of ocular surface safety and preservative e‹cacy. BAKC 12 , which is dodecyl dimethylbenzylammonium chloride, and BAKmix, which is the mixture of dodecyl, tetradecyl and hexadecyl dimethylbenzylammonium chloride were used in this study. The eŠects of BAKC 12 concentrations and the BAK types, BAKC 12 and BAKmix, in ta‰uprost ophthalmic solution on ocular surface safety were evaluated using the in vitro SV 40-immobilized human corneal epithelium cell line (HCE-T). Following treatments of Ta‰uprost ophthalmic solutions with BAKC 12 , its concentration dependency was observed on cell viability of HCE-T. The cell viability of HCE-T after treatment of these solutions with 0.001％ to 0.003％ BAKC 12 for 5 minutes were the same level as that after treatment of the solution without BAK. Ta‰uprost ophthalmic solution with 0.01％ BAKC 12 was safer for the ocular surface than the same solution with 0.01％ BAKmix. Preservatives-eŠectiveness tests of ta‰uprost ophthalmic solutions with various concentrations of BAKC 12 were performed according to the Japanese Pharmacopoeia (JP), and solutions with more than 0.0005％ BAKC 12 conformed to JP criteria. It was concluded that 0.0005％ to 0.003％ of BAKC 12 in ta‰uprost ophthalmic solution was optimal, namely, well-balanced from the points of ocular surface safety and preservative e‹cacy.

No abstract