RESUMO
Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aß) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aß aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aß deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aß neurotoxicity by both degrading FA and reducing FA-induced Aß assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aß oligomerization and extracellular Aß-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Xantofilas , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide , Lipossomos , Camundongos Transgênicos , Fenótipo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Água , Xantofilas/administração & dosagem , Xantofilas/químicaRESUMO
It is difficult for traditional sutures, which are usually braided by microfibers, to load drugs or growth factors. To develop a novel species of suture, in this study, a core-sheath yarn was fabricated by surrounding Poly (lactic-co-glycolic acid) (PLGA) microfibers with electrospun PLGA nanofibers using a custom electrospinning equipment with two needles and a rotating funnel. The resulting yarn shows enough mechanical strength to be used as sutures. The capillary action, which is caused by the structure of the core-sheath yarn, enabled the PLGA yarn to easily absorb a growth factor. Thus TGF-ß1 was loaded to the core-sheath yarn ensuring that the suture has a tissue repairing function. Human umbilical vein endothelial cells grew faster on TGF-ß1 loaded core-sheath yarn than on the core-sheath yarn without growth factor. This core-sheath yarn fabrication method has the potential to be used in the development of functional sutures.
Assuntos
Materiais Revestidos Biocompatíveis/química , Ácido Láctico/química , Ácido Poliglicólico/química , Suturas , Fator de Crescimento Transformador beta1/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Técnicas Eletroquímicas , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/ultraestrutura , Humanos , Microscopia Eletrônica de Varredura , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Fator de Crescimento Transformador beta1/administração & dosagemRESUMO
Tracheal stenosis is one of major challenging issues in clinical medicine because of the poor intrinsic ability of tracheal cartilage for repair. Tissue engineering provides an alternative method for the treatment of tracheal defects by generating replacement tracheal structures. In this study, we fabricated coaxial electrospun fibers using poly(L-lactic acid-co-caprolactone) and collagen solution as shell fluid and kartogenin solution as core fluid. Scanning electron microscope and transmission electron microscope images demonstrated that nanofibers had uniform and smooth structure. The kartogenin released from the scaffolds in a sustained and stable manner for about 2 months. The bioactivity of released kartogenin was evaluated by its effect on maintain the synthesis of type II collagen and glycosaminoglycans by chondrocytes. The proliferation and morphology analyses of mesenchymal stems cells derived from bone marrow of rabbits indicated the good biocompatibility of the fabricated nanofibrous scaffold. Meanwhile, the chondrogenic differentiation of bone marrow mesenchymal stem cells cultured on core-shell nanofibrous scaffold was evaluated by real-time polymerase chain reaction. The results suggested that the core-shell nanofibrous scaffold with kartogenin could promote the chondrogenic differentiation ability of bone marrow mesenchymal stem cells. Overall, the core-shell nanofibrous scaffold could be an effective delivery system for kartogenin and served as a promising tissue engineered scaffold for tracheal cartilage regeneration.