First-aid hemostatic agents for acute bleeding can save lives in emergency situations. However, rapid hemostasis remains challenging when uncontrolled hemorrhage occurs on lethal noncompressible and irregular wounds. Herein, cellulosebased cryogel microspheres with deliberately customized micromorphologies for ultrafast water transportation and diffusion, including the shark skin riblet-inspired wrinkled surface with low fluid drag and the hydrophilic nanoporous 3D networks, are developed to deal with the acute noncompressible bleeding within seconds. These cryogel microspheres can rapidly absorb a large amount of blood over 6 times their own weight in 10 s and form a robust barrier to seal a bleeding wound without applying pressure. Remarkably, massive bleeding from a cardiac penetrating hole is effectively stopped using the microspheres within 20 s and no blood leakage is observed after 30 min. Additionally, these microspheres could be readily removed without rebleeding and capillary thrombus, which is highly favorable to rapid hemostasis in emergency rescue.
2019) Ultra-small micelles based on polyoxyl 15 hydroxystearate for ocular delivery of myricetin: optimization, invitro, and invivo evaluation, Drug Delivery, 26:1, 158-167, ABSTRACT The aim was to develop a nanocarrier based on polyoxyl 15 hydroxystearate (KolliphorV R HS15, HS15) micelles for the solubility, stability, and ocular delivery of myricetin (Myr). An optimized ratio of HS15 and Myr was prepared to fabricate HS15-Myr micelle ophthalmic solution. Myr-encapsulating HS15 micelles (HS15-Myr micelles) were subjected to physicochemical characterizations. The chemical stability of Myr in HS15 micelles and storage stability of HS15-Myr micelle ophthalmic solutions were evaluated. In vitro parallel artificial membrane permeability assay and antioxidant activity of Myr in HS15 micelles were also measured. In vivo ocular tolerance, corneal permeation, and anti-inflammatory efficacy studies were conducted following ocular topical administration. HS15-Myr micelles were successfully prepared and presented transparent appearance with high encapsulation (96.12 ± 0.31%), ultra-small micelle size (a mean diameter of 12.17 ± 0.73 nm), uniform size distribution (polydispersity index [PDI] ¼ 0.137 ± 0.013), and negative surface charge (À [4.28 ± 0.42] mV). Myr in HS15 micelle solution demonstrated higher aqueous stability than the free Myr solution among the accepted pH range for eyedrops. HS15-Myr micelle ophthalmic solution demonstrated high storage stability at 4 C and 25 C. HS15 micelles could significantly improve in vitro antioxidant activity and faster membrane permeation of Myr. No irritations or corneal damage were revealed in rabbit eyes after ocular administration of HS15-Myr micelle solution.In vivo corneal permeation study demonstrated that HS15-Myr micelles could penetrate the cornea efficiently in mouse eyes. Further, HS15-Myr micelles also demonstrated significant in vivo anti-inflammatory activity. It can be concluded that HS15 micelles are a potential ophthalmic delivery nanocarrier for poorly soluble drugs such as Myr. ARTICLE HISTORY
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