PLGA-functionalized Quercetin Nanoparticles With Antibacterial Activity And Its Potential Use In Alzheimer's Disease

Nanotechnology plays an important role in the most of research fields such as medicine,biology,and so on,attracting numerous attentions,owing to their potential for achieving specific processes and especially in biological and pharmaceutical applications.Nanoparticles?NPs?have peculiar and well defined properties that distinguish them from their bulk chemical counterparts,for example,large surface area to volume ratio.The NPs therapeutics has the potential to significantly alter the in vivo biological properties of the pharmaceutically active agents that they carry.Microorganisms are a major problem for current medicine.Increased resistance of bacteria to disinfection and antimicrobial treatment poses a serious public health threat worldwide.Therefore,there is an urgent need for designing new alternative bactericidal agents.Nanoscale materials bring new possibilities in the development of effective antimicrobial agents.Dysfunctional interaction of amyloid-??A??with excess metal ions is proved to be related to the etiology of Alzheimer's disease?AD?.The accumulation of metals such as iron,copper,and zinc within the senile plaques can reach levels of up to 400,950,and 1100 mm,respectively,which is 3-5 times higher in concentration as compared to healthy brain.AD is an age related cognitive disorder associated with the decline of learning and memory brought on by a loss of neuronal function.Hence,disruption of these metal-peptide interactions with NPs reducing the harmful effects of excess metal deposition holds considerable promise as a therapeutic strategy to combat this disease.Quercetin?QT?exists wildly in nature,has provided ample evidence of their bioactive properties such as antibacterial effects have invested to developing novel antibacterial strategies against pathogenic bacteria.Furthermore,it was suggested to attenuate the toxic effects of amyloid peptides in several cell culture lines and neurons.PLGA possess excellent biodegradability and biocompatibility and it is extensively used in the construction of drug delivery formulations.PLGA,established safety profile,have been approved by USFDA.With this background,the present study was undertaken to develop PLGA-functionalized quercetin?PLGA@QT?NPs with uniform,spherical,and with the mean diameter of 100-150 nm.We used Escherichia coli?E.coli?and Micrococcus tetragenus?M.tetragenus?as model bacterial and tested the antibacterial effects of PLGA@QT NPs against them.The PLGA@QT NPs produced stronger antibacterial activity to E.coli than that to M.tetragenus through disrupting bacterial cell wall integrity.The antibacterial ratio was increased with increasing its dosages and incubation time.We had studied PLGA@QT NPs behaviors in vivo.PLGA@QT NPs appeared to be an excellent in vivo anti-infected as therapeutic agent without exhibiting noticeable toxicity to the treated mice.As we probe deeper into its potential not only as potential therapeutic agents for the treatment of AD but also as one with pronounced low toxicity properties.The next was to investigate the effects of PLGA@QT NPs on inhibited and disassembled A?₄₂fibrils.We used human neuroblastoma?SH-SY5Y?cells to perform real-time cell analysis assay?RTCA?to probe the potential cytotoxicity of PLGA@QT NPs.At any given time point,the cell index?CI?decreases as PLGA@QT NPs concentration increases,demonstrating a concentration-dependent cytotoxic effect on SH-SY5Y cells and PLGA@QT NPs partially blocked Zn²⁺/A?₄₂2 system induced toxicity.Notably,the Morris Water Maze?MWM?and Novel Object Recognition?NOR?tests showed that the PLGA@QT NPs treatment ameliorated mice cognition and memory impairments in mice insulted by AD.Data on histological analysis are encouraging for further investigations on properties of PLGA@QT NPs along with the absence of toxic effects in BALB/c nude mice.The low cytotoxicity of PLGA@QT NPs to mice is the fundamental requirement for the therapeutic application in AD.However,the specific mechanism of PLGA@QT NPs in AD needs further research.We expect these results are thus expected to advance the field of synthetic NPs and to increase therapeutic efficacy and safety profile of the combination toward expanding the horizon of nanomedicine.