Drug delivery
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Myricetin (Myr) is a naturally occurring flavonoid exhibiting diverse biological and pharmacological properties, but its characteristics such as water insolubility, poor aqueous stability, and poor bioavailability limit its clinical application, including in ophthalmology. To increase its clinical application in ophthalmology, Myr was designed to be encapsulated in a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG) polymeric micelles to increases its aqueous solubility, stability, and corneal permeability to promote its efficacy in eye disease treatments. Thus, the Myr micelle ophthalmic solution was prepared and characterized encapsulation efficiency (EE), micelle size, and zeta potential. ⋯ In rabbits, the Myr micelle ophthalmic solution displayed good in vitro cellular tolerance. Remarkable improvements in in vitro cellular uptake and in vivo corneal permeation were also observed in the Myr micelle ophthalmic solution, and significant improvements in the in vitro antioxidant activity and in vivo anti-inflammatory efficacy were also obtained. Overall, these results supported that the Myr micelle ophthalmic solution could be a promising nanomedicine for ocular tissues.
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The aim was to develop a nanocarrier based on polyoxyl 15 hydroxystearate (Kolliphor® 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. ⋯ 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.
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Osteoarthritis (OA) is the most common form of joint disease and a leading cause of physical disability, there is an urgent need to attenuate the progression of OA. Intra-articular (IA) injection is an effective treatment for joints diseases, however, the therapeutic effects mostly depend on the efficacy of drug duration in joints. Drug delivery system can provide drug-controlled release and reduce the number of IA injection. ⋯ By contrast, IA injection of PN-KGN showed less cartilage degeneration with significant lower OARSI scores even at 12 weeks, indicating PN-KGN could further arrest the development of OA. Immunohistochemistry also validated that IA injection of PN-KGN retained the normal compositions of cartilage matrix, with much stronger Col II staining and less Col I staining. In conclusion, IA injection of PN-KGN is a better potential strategy to treat OA, with long-time cartilage protection and less IA injections.
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Persistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a robust platform for drug delivery. This study aims to develop an SAP-based carrier to slow release MT for enhancing its long-term therapeutic potency on AKI. ⋯ Compared to IRI and free MT mice, SAP-MT mice exerted reduced renal mitochondria-produced ROS (mtROS) and improved mitochondrial biogenesis and architecture. Consequently, SAP-MT mice showed less renal tubular cell apoptosis, kidney injury marker kidney injury molecule-1 (Kim-1) expression, lower level of pro-inflammatory factors expression, and macrophages infiltration than those of IRI and free MT mice. This study suggested that SAP-MT ameliorated IRI due to its extended mitochondrial protection role than free MT and thus improved the long-term outcomes of AKI.
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Currently, traumatic brain injury (TBI) is the leading cause of death or disabilities in young individuals worldwide. The multi-complexity of its pathogenesis as well as impermeability of the blood-brain barrier (BBB) makes the drug choice and delivery very challenging. The brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell survival and long-term memory. ⋯ This study also showed using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX 3 h post-injury prolonged the latent time in mice with TBI thereby reversing cognitive deficits caused by brain trauma. Finally, neurological severity score test demonstrated that our compound efficiently reduced the scores at day 7 after the injury indicating the improvement of neurological deficit in animals with TBI. This study shows that PLGA nanoparticles coated with PX effectively delivered BDNF into the brain, and improved neurological and cognitive deficits in TBI mice, thereby providing a neuroprotective effect.