Our aim is to reduce the side effects and increase the efficiency of donepezil by formulating donepezil-loaded poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) nanoparticles (NPs) directly targeting amyloid beta (Aβ) fibrils in the brain and evaluate behavioral changes in this fibril model of AD.AD model was developed by intracerebroventricular injection of pre-aggregated β25-35 fibrils. Rats were intravenously administered either solvent, donepezil-loaded NPs (15µg/kg) or free donepezil (1mg/kg) 3 times for a week except for naïve controls. The effect of treatments on anxiety, motor functions, and cognitive functions was tested by elevated plus maze, locomotor activity, novel object recognition, and Morris's water maze tests, respectively.Accumulation of Aβ25-35 fibrils in brain sections was confirmed. Anxiety-like behavior was observed in the Aβ Alzheimer and free donepezil treatment groups while donepezil-loaded NP treatment showed hypo-anxiety-like behavior. Donepezil-loaded NPs were successful in treatment of short-term memory deficit better than free donepezil injection. In Morris's water maze, both donepezil-loaded NPs and free donepezil groups found the platform in shorter time compared to Aβ Alzheimer group. In locomotor activity test, both donepezil treated groups moved less than the Aβ Alzheimer group and naïve controls. After the pharmacological experiments, acetylcholinesterase activity was determined and showed an increase in Aβ Alzheimer group compared to controls. Donepezil-loaded NPs inhibited the acetylcholinesterase activity more efficiently than the free donepezil group.Targeting with donepezil-loaded PLGA-b-PEG-NPs increases efficiency, helps to inhibit acetylcholinesterase activity more substantially, improves cognitive decline due to its longer duration of action and destabilizing effect on amyloid fibrils.
This work focuses on the synthesis of oil-layered microbubbles using two microfluidic T-junctions in series and evaluation of the effectiveness of these microbubbles loaded with doxorubicin and curcumin for cell invasion arrest from 3D spheroid models of triple negative breast cancer (TNBC), MDA-MB-231 cell line. Albumin microbubbles coated in the drug-laden oil layer were synthesized using a new method of connecting two microfluidic T-mixers in series. Double-layered microbubbles thus produced consist of an innermost core of nitrogen gas encapsulated in an aqueous layer of bovine serum albumin (BSA) which in turn, is coated with an outer layer of silicone oil. In order to identify the process conditions leading to the formation of double-layered microbubbles, a regime map was constructed based on capillary numbers for aqueous and oil phases. The microbubble formation regime transitions from double-layered to single layer microbubbles and then to formation of single oil droplets upon gradual change in flow rates of aqueous and oil phases. In vitro dissolution studies of double-layered microbubbles in an air-saturated environment indicated that a complete dissolution of such bubbles produces an oil droplet devoid of a gas bubble. Incorporation of doxorubicin and curcumin was found to produce a synergistic effect, which resulted in higher cell deaths in 2D monolayers of TNBC cells and inhibition of cell proliferation from 3D spheroid models of TNBC cells compared to the control.
Antibacterial nanofibers have a great potential for effective treatment of infections. They act as drug reservoir systems that release higher quantities of antibacterial agents/drug in a controlled manner at infection sites and prevent drug resistance, while concomitantly decreasing the systemic toxicity. With this drug delivery system, it is also possible to achieve multiple drug entrapment and also simultaneous or sequential release kinetics at the site of action. Therefore, advances in antibacterial nanofibers as drug delivery systems were overviewed within this article. Recently published data on antibacterial drug delivery was also summarised to provide a view of the current state of art in this field. Although antibacterial use seems to be limited and one can ask that 'what is left to be discovered?'; recent update literatures in this field highlighted the use of nanofibers from very different perspectives. We believe that readers will be benefiting this review for enlightening of novel ideas.
Abstract The present study aspires towards fabricating core‐sheath fibrous scaffolds by state‐of‐the‐art pressurized gyration for bone tissue engineering applications. The core‐sheath fibers comprising dual‐phase poly‐ε‐caprolactone (PCL) core and polyvinyl alcohol (PVA) sheath are fabricated using a novel “co‐axial” pressurized gyration method. Hydroxyapatite (HA) nanocrystals are embedded in the sheath of the fabricated scaffolds to improve the performance for application as a bone tissue regeneration material. The diameter of the fabricated fiber is 3.97 ± 1.31 µm for PCL‐PVA/3%HA while pure PCL–PVA with no HA loading gives 3.03 ± 0.45 µm. Bead‐free fiber morphology is ascertained for all sample groups. The chemistry, water contact angle and swelling behavior measurements of the fabricated core‐sheath fibrous scaffolds indicate the suitability of the structures in cellular activities. Saos‐2 bone osteosarcoma cells are employed to determine the biocompatibility of the scaffolds, wherein none of the scaffolds possess any cytotoxicity effect, while cell proliferation of 94% is obtained for PCL–PVA/5%HA fibers. The alkaline phosphatase activity results suggest the osteogenic activities on the scaffolds begin earlier than day 7. Overall, adaptations of co‐axial pressurized gyration provides the flexibility to embed or encapsulate bioactive substances in core‐sheath fiber assemblies and is a promising strategy for bone healing.
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