Isolation and characterization of a relatively broad-spectrum phage against Escherichia coli.

Multiple pathogenic types or serotypes restrict treatment for colibacillosis. In addition, rising antibiotic resistance has heightened public awareness to prevent and control pathogenic Escherichia coli. The bacteriophage is a viable technique to treat colibacillosis as an alternative to antibiotics. In this study, PH444, a relatively broad-spectrum obligate lytic phage, was screened from 48 Shiga toxin-producing Escherichia coli (STEC) phages isolated from farm manure samples and sewage samples in order to conduct genome-wide analysis, biological characterization, and a bacterial challenge experiment in milk. The results demonstrated that PH444 was a T7-like phage with a double-stranded DNA of 115,111 bp that belongs to the Kuravirus and was stable at temperatures between 4 and 50 °C and a pH range of 3 to 11. After adding PH444, the bacterial load in milk could be reduced from 3 × 103 PFU/ mL to zero within 1 h. In consideration of the biological properties of phage PH444, it was, therefore, demonstrated that PH444 has the potential to be used in phage biocontrol.

Mesoporous Silica Carrier-Based Composites for Taste-Masking of Bitter Drug: Fabrication and Palatability Evaluation.

Palatability is one of the most critical characteristics of oral preparations. Therefore, the exploration of new techniques to mask the aversive taste of drugs is in continuous demand. In this study, we fabricated and characterized composites based on mesoporous silica (MPS) that consisted of MPS, a bitter drug, and release regulators. We conducted a palatability evaluation to assess the taste-masking efficacy of the composites. The composites were prepared using the dry impregnation method combined with hot-melt extrusion. Morphology and components distribution in composites were characterized by scanning electron microscopy, confocal laser scanning microscopy, X-ray photoelectron spectroscopy, powder flow properties evaluation, and nitrogen-sorption measurement. The results demonstrated that drugs mainly existed in the inner pore of composites, and release regulators existed in the inner pore and covered the composites' surface. Interactions among the composite components were studied using powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. The drug loaded into the composites was amorphous, and an intermolecular interaction occurred between the drug and the MPS. Taste-masked composites significantly reduced drug release levels under mouth conditions; thus, they prevented the interaction of the dissolved drug with taste receptors and improved palatability. An electronic tongue evaluation and a human taste panel assessment confirmed the better palatability of taste-masked composites. Moreover, the desired drug release behavior can be adjusted by choosing an appropriate release regulator, with stronger hydrophobicity of release regulators resulting in slower drug release. This work has provided new insights into taste-masking strategies for drugs with unpleasant tastes.

RVG-functionalized reduction sensitive micelles for the effective accumulation of doxorubicin in brain.

BACKGROUND: Glioblastoma is a lethal neoplasm with few effective therapy options. As a mainstay in the current treatment of glioma at present, chemotherapeutic agents usually show inadequate therapeutic efficiency due to their low blood brain barrier traversal and brain targeting, together with tumor multidrug resistance. Novel treatment strategies are thus urgently needed to improve chemotherapy outcomes. RESULTS: Here, we report that nanomedicines developed by functionalizing the neurotropic rabies virus-derived polypeptide, RVG, and loading reduction-sensitive nanomicelles (polymer and doxorubicin) enable a highly specific and efficacious drug accumulation in the brain. Interestingly, curcumin serves as the hydrophobic core of the polymer, while suppressing the major efflux proteins in doxorubicin-resistant glioma cells. Studies on doxorubicin-resistant rat glioma cells demonstrate that the RVG-modified micelles exhibit superior cell entry and antitumor activity. In vivo research further showed that RVG modified nanomicelles significantly enhanced brain accumulation and tumor inhibition rate in mice, leading to a higher survival rate with negligible systemic toxicity. Moreover, effective suppression of recurrence and pulmonary metastatic nodules were also determined after the RVG-modified nanomicelles treatment. CONCLUSIONS: The potential of RVG-modified nanomicelles for glioma was demonstrated. Brain accumulation was markedly enhanced after intravenous administration. This unique drug delivery nanoplatform to the brain provides a novel and powerful therapeutic strategy for the treatment of central nervous system disorders including glioma.

A sonosensitiser-based polymeric nanoplatform for chemo-sonodynamic combination therapy of lung cancer.

BACKGROUND: Lung cancer is the most common type of tumour worldwide. Its relative lethality is considerably high. However, since the tumour tissues are located deep within the human body, traditional technologies, such as photodynamic therapy, do not have the desired effect. Sonosensitisers can penetrate deeply into tissues, and sonodynamic therapy (SDT) effectively inhibits tumours by generating reactive oxygen species. Ultrasound can also penetrate deeply, with a favourable tumour inhibition effect. RESULTS: A redox/ultrasound-responsive Rhein-chondroitin sulphate-based nano-preparation encapsulating docetaxel was fabricated. The nanoparticles displayed increased cellular uptake with quick drug release, good stability, and a monodispersed form in the physiological environment. Rhein induced apoptosis and altered mitochondrial membrane potential, which enhanced the expression of apoptosis-related proteins. SDT inhibited the metastasis and angiogenesis of cancer cells and activated anti-tumour capacity by reducing the expression of M2 macrophages. CONCLUSIONS: The potential of Rhein for SDT was demonstrated. Production of reaction oxygen species was markedly enhanced after ultrasound treatment. The nanoplatform enhanced the synergistic anti-tumour effects of SDT and chemotherapeutic efficacy. The approach was biocompatibility. The findings could inform investigations of chemo-SDT for different cancers.

A molybdenum oxide-based degradable nanosheet for combined chemo-photothermal therapy to improve tumor immunosuppression and suppress distant tumors and lung metastases.

Molybdenum oxide (MoOx) nanosheets have drawn increasing attention for minimally invasive cancer treatments but still face great challenges, including complex modifications and the lack of efficient accumulation in tumor. In this work, a novel multifunctional degradable FA-BSA-PEG/MoOx nanosheet was fabricated (LA-PEG and FA-BSA dual modified MoOx): the synergistic effect of PEG and BSA endows the nanosheet with excellent stability and compatibility; the FA, a targeting ligand, facilitates the accumulation of nanosheets in the tumor. In addition, DTX, a model drug for breast cancer treatment, was loaded (76.49%, 1.5 times the carrier weight) in the nanosheets for in vitro and in vivo antitumor evaluation. The results revealed that the FA-BSA-PEG/MoOx@DTX nanosheets combined photothermal and chemotherapy could not only inhibit the primary tumor growth but also suppress the distant tumor growth (inhibition rate: 51.7%) and lung metastasis (inhibition rate: 93.6%), which is far more effective compared to the commercial Taxotere®. Exploration of the molecular mechanism showed that in vivo immune response induced an increase in positive immune responders, suppressed negative immune suppressors, and established an inflammatory tumor immune environment, which co-contributes towards effective suppression of tumor and lung metastasis. Our experiments demonstrated that this novel multifunctional nanosheet is a promising platform for combined chemo-photothermal therapy.

A review of stimuli-responsive polymeric micelles for tumor-targeted delivery of curcumin.

Despite a potential drug with multiple pharmacological activities, curcumin has disadvantages of the poor water solubility, rapid metabolism, low bioavailability, which considerably limit its clinical application. Currently, polymeric micelles (PMs) have gained widespread concern due to their advantageous physical and chemical properties, easy preparation, and biocompatibility. They can be used to improve drug solubility, prolong blood circulation time, and allow passive targeted drug delivery to tumor through enhanced penetration and retention effect. Moreover, studies focused on tumor microenvironment offer alternatives to design stimulus-responsive smart PMs based on low pH, high levels of glutathione, altered enzyme expression, increased reactive oxygen species production, and hypoxia. There are various external stimuli, such as light, ultrasound, and temperature. These endogenous/exogenous stimuli can be used for the research of intelligent micelles. Intelligent PMs can effectively load curcumin with improved solubility, and intelligently respond to release the drug at a controlled rate at targeted sites such as tumors to avoid early release, which markedly improves the bioavailability of curcumin. The present review is aimed to discuss and summarize recent developments in research of curcumin-loaded intelligent PMs based on endogenous and exogenous stimuli, and facilitates the development of novel delivery systems for future research.

Erratum: Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma.

The authors informed the journal that an error occurred in their manuscript. Figure 2D was mistakenly overlooked by the authors during the galley proof stage. Reference: 1. Zhang X, Zhao L, Zhai G, Ji J, Liu A. Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma. Med Sci Monit, 2019; 25: 9737-9751. doi: 10.12659/MSM.918899.

Inhibition of the adenosinergic pathway: the indispensable part of oncological therapy in the future.

In recent years, immunotherapy has produced many unexpected breakthroughs in oncological therapy; however, it still has many deficiencies. For example, the number of patients who are unresponsive to anti-programmed death-ligand 1 (PD-L1), anti-cytotoxic T-like antigen-4 (CTLA4), and anti-programmed death-1 (PD1) therapies cannot be ignored, and the search for an undiscovered immunosuppressive pathway is imminent. Five decades ago, researchers found that activation of the adenosinergic pathway was negatively correlated with prognosis in many cancers. This review describes the entire process of the adenosinergic pathway in the tumor microenvironment and the mechanism of immunosuppression, which promotes tumor metastasis and drug resistance. Additionally, the review explores factors that regulate this pathway, including signaling factors secreted by the tumor microenvironment and certain anti-tumor drugs. Additionally, the combination of adenosinergic pathway inhibitors with chemotherapy, checkpoint blockade therapy, and immune cell-based therapy is summarized. Finally, certain issues regarding treatment via inhibition of this pathway and the use of targeted nanoparticles to reduce adverse reactions in patients are put forward in this review. Graphical Abstract The inhibitors of adenosinergic pathway loaded nanoparticles enter tumor tissue through EPR effect, and inhibit adenosinergic pathway to enhance or restore the effect of immune checkpoint blockade therapy, chemotherapies and immune cell-based therapy. Note: EPR means enhanced penetration and retention, × means blockade.

Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma.

BACKGROUND This study aimed to prepare doxorubicin- and tetrahydrocurcumin-loaded and transferrin-modified PEG-PLGA nanoparticles (Tf-NPs-DOX-THC) for enhanced and synergistic chemoradiotherapy. MATERIAL AND METHODS Tf-NPs-DOX-THC were prepared via the double-emulsion method. The morphologies and particle sizes of the prepared nanoparticles were examined by TEM and DLS, respectively. The in vitro MTT, apoptosis, and clone formation assays were performed to detect the proliferation and radiosensitivity of cells with various treatments. Cellular uptake assay was also conducted. The tissue distribution of Tf-NPs was investigated by ex vivo DOX fluorescence imaging. The in vivo tumor growth inhibition efficiency of various treatments was evaluated in orthotopic C6 mouse models and C6 subcutaneously grafted mouse models. RESULTS Tf-NPs-DOX-THC exhibited high drug-loading efficiency (6.56±0.32%) and desirable particle size (under 250 nm). MTT, apoptosis, and clone formation assays revealed the enhanced anti-cancer activity and favorable radiosensitizing effect of Tf-NPs-DOX-THC. Strong fluorescence was observed in the brains of mice treated with Tf-NPs-DOX. The in vitro release of drug from nanoparticles was in a pH-sensitive manner. Tf-NPs-DOX-THC in combination with radiation also achieved favorable anti-tumor efficacy in vivo. CONCLUSIONS All results suggest that a combination of Tf-NPs-DOX-THC and radiation is a promising strategy for synergistic and sensitizing chemoradiotherapy of glioma.

Lipid nanoparticles loading triptolide for transdermal delivery: mechanisms of penetration enhancement and transport properties.

BACKGROUND: In recent years, nanoparticles (NPs) including nanostructured lipid carries (NLC) and solid lipid nanoparticles (SLN) captured an increasing amount of attention in the field of transdermal drug delivery system. However, the mechanisms of penetration enhancement and transdermal transport properties of NPs are not fully understood. Therefore, this work applied different platforms to evaluate the interactions between skin and NPs loading triptolide (TPL, TPL-NLC and TPL-SLN). Besides, NPs labeled with fluorescence probe were tracked after administration to investigate the dynamic penetration process in skin and skin cells. In addition, ELISA assay was applied to verify the in vitro anti-inflammatory effect of TPL-NPs. RESULTS: Compared with the control group, TPL-NPs could disorder skin structure, increase keratin enthalpy and reduce the SC infrared absorption peak area. Besides, the work found that NPs labeled with fluorescence probe accumulated in hair follicles and distributed throughout the skin after 1 h of administration and were taken into HaCaT cells cytoplasm by transcytosis. Additionally, TPL-NLC could effectively inhibit the expression of IL-4, IL-6, IL-8, IFN-γ, and MCP-1 in HaCaT cells, while TPL-SLN and TPL solution can only inhibit the expression of IL-6. CONCLUSIONS: TPL-NLC and TPL-SLN could penetrate into skin in a time-dependent manner and the penetration is done by changing the structure, thermodynamic properties and components of the SC. Furthermore, the significant anti-inflammatory effect of TPL-NPs indicated that nanoparticles containing NLC and SLN could serve as safe prospective agents for transdermal drug delivery system.

Preparation and in vitro and in vivo evaluation of quercetin-loaded mixed micelles for oral delivery.

Quercetin (QT) is a plant polyphenol with various pharmacological properties. However, the low water solubility limits its therapeutic efficacy. In the present study, QT-loaded sodium taurocholate-Pluronic P123 (QT-loaded ST/P123) mixed micelles were developed and characterized, and the effect of the formulation on improving the water solubility of QT was investigated. QT-loaded ST/P123 mixed micelles were prepared by thin film hydration-direct dissolution and optimized by uniform design. The optimal formulation possessed high drug loading (12.6%) and entrapment efficiency (95.9%) in small (16.20 nm) spherically-shaped micelles. A low critical micelle concentration indicated that the micelles were stable, and they showed a sustained release pattern, as determined in vitro in simulated gastric fluid and intestinal fluid. Pharmacokinetic evaluation showed the Cmax and AUC0-24 were 1.8-fold and 1.6-fold higher than the QT suspension. The present results indicate that QT-loaded ST/P123 micelles are potential candidates to improve the solubility and oral bioavailability of QT.

Metabolite identification of the antimalarial naphthoquine using liquid chromatography-tandem high-resolution mass spectrometry in combination with multiple data-mining tools.

Naphthoquine (NQ) is one of important partner drugs of artemisinin-based combination therapy (ACT), which is recommended for the treatment of uncomplicated Plasmodium falciparum. NQ shows a high cure rate after a single oral administration. It is absorbed quickly (time to peak concentration 2-4 h) and has a long elimination half-life (255 h). However, the metabolism of NQ has not been clarified. In this work, the metabolite profiling of NQ was studied in six liver microsomal incubates (human, cynomolgus monkey, beagle dog, mini pig, rat and CD1 mouse), seven recombinant CYP enzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and rat (plasma, urine, bile and feces) using liquid chromatography tandem high-resolution LTQ-Orbitrap mass spectrometry (HRMSn ) in conjunction with online hydrogen/deuterium exchange. The biological samples were pretreated by protein precipitation and solid-phase extraction. For data processing, multiple data-mining tools were applied in tandem, i.e. background subtraction and followed by mass defect filter. NQ metabolites were characterized by accurate MS/MS fragmentation characteristics, the hydrogen/deuterium exchange data and cLogP simulation. As a result, five phase I metabolites (M1-M5) of NQ were characterized for the first time. Two metabolic pathways were involved: hydroxylation and N-oxidation. This study demonstrates that LC-HRMSn in combination with multiple data-mining tools in tandem can be a valuable analytical strategy for rapid metabolite profiling of drugs.

Advanced nanocarriers based on heparin and its derivatives for cancer management.

To obtain a satisfying anticancer effect, rationally designed nanocarriers are intensively studied. In this field, heparin and its derivatives have been widely attempted recently as potential component of nanocarriers due to their unique biological and physiochemical features, especially the anticancer activity. This review focuses on state-of-the-art nanocarriers with heparin/heparin derivatives as backbone or coating material. At the beginning, the unique advantages of heparin used in cancer nanotechnology are discussed. After that, different strategies of heparin chemical modification are reviewed, laying the foundation of developing various nanocarriers. Then a systematic summary of diverse nanoparticles with heparin as component is exhibited, involving heparin-drug conjugate, polymeric nanoparticles, nanogels, polyelectrolyte complex nanoparticles, and heparin-coated organic and inorganic nanoparticles. The application of these nanoparticles in various novel cancer therapy (containing targeted therapy, magnetic therapy, photodynamic therapy, and gene therapy) will be highlighted. Finally, future challenges and opportunities of heparin-based biomaterials in cancer nanotechnology are discussed.

Curcumin-Loaded Lipid Cubic Liquid Crystalline Nanoparticles: Preparation, Optimization, Physicochemical Properties and Oral Absorption.

In order to improve the oral absorption of curcumin, curcumin-loaded lipid cubic liquid crystalline nanoparticles were prepared and evaluated in vitro and in vivo. The hot and high-pressure homogenization method was used to prepare the nanoparticles. The formulation and process were optimized by uniform design with drug loading and entrapment efficiency as index, and physicochemical properties were also investigated. Spherical nanoparticles were observed under transmission electron microscope (TEM), with average particle size of 176.1 nm, zeta potential of -25.19 mV, average drug loading of (1.5 ± 0.2)% and entrapment efficiency of (95 ± 1.8)%. The in vitro release of curcumin from the nanoparticle formulation showed a sustained property, while the pharmacokinetics results after oral administration of curcumin loaded lipid cubic liquid crystalline nanoparticles in rat showed that the oral absorption of curcumin fitted one-compartment model and relative bioavailability was 395.56% when compared to crude curcumin. It can be concluded from these results that the lipid cubic liquid crystalline nanoparticles, as carriers, can markedly improve the oral absorption of curcumin.

Preparation and Characterization of Puerarin-Loaded Lipid Nanocapsules.

The puerarin-loaded lipid nanocapsules (PUE-LNCs), composed of labrafac, lipoid and water, were prepared with a phase inversion procedure. The formulation was optimized by simplex lattice design and characterized for its size, zeta potential and in vitro drug release. The results showed that the PUE-LNCs performed a homogeneous typical core-shell structure under transmission electron microscope (TEM). The entrapment efficiency and drug loading were 56.61 ± 0.27% and 2.62 ± 0.12%, respectively. In vitro drug release revealed the PUE-LNCs showed a controlled-release manner in both artificial simulated gastric juice (pH 1.0) and artificial simulated intestinal fluid (pH 6.8). Based on the aforementioned results, it should now allow a promising tuning for further applications of LNCs as a drug delivery system for puerarin.

Ethosomes for skin delivery of ropivacaine: preparation, characterization and ex vivo penetration properties.

Ropivacaine, a novel long-acting local anesthetic, has been proved to own superior advantage. However, Naropin® Injection, the applied form in clinic, can cause patient non-convenience. The purpose of this study was to formulate ropivacaine (RPV) in ethosomes and evaluate the potential of ethosome formulation in delivering RPV transdermally. The RPV-loaded ethosomes were prepared with thin-film dispersion technique and the formulation was characterized in terms of size, zeta potential, differential scanning calorimetry (DSC) analysis and X-ray diffraction (XRD) study. The results showed that the optimized RPV-ethosomes displayed a typical lipid bilayer structure with a narrow size distribution of 73.86 ± 2.40 nm and drug loading of 8.27 ± 0.37%, EE of 68.92 ± 0.29%. The results of DSC and XRD study indicated that RPV was in amorphous state when encapsulated into ethosomes. Furthermore, the results of ex vivo permeation study proved that RPV-ethosomes could promote the permeability in a high-efficient, rapid way (349.0 ± 11.5 µg cm(-2) at 12 h and 178.8 ± 7.1 µg cm(-2) at 0.5 h). The outcomes of histopathology study forecasted that the interaction between ethosomes and skin could loosen the tight conjugation of corneocyte layers and weaken the permeation barrier. In conclusion, RPV-ethosomes could be a promising delivery system to encapsulate RPV and deliver RPV for transdermal administration.

An active transport dual adaptive nanocarrier designed to overcome the corneal microenvironment for neovascularization therapy.

The eyes have a complicated microenvironment with many clearance mechanisms, making it challenging for effective drug delivery to the targeted areas of the eyes. Substrate transport mediated by active transporters is an important way to change drug metabolism in the ocular microenvironment. We designed multifunctional, dual-adaptive nanomicelles (GSCQ@NTB) which could overcome multiple physiological barriers by acting on both the efflux transporter and influx transporter to achieve deep delivery of the P-gp substrate in the cornea. Specifically, an effective "triple" antiangiogenic agent, nintedanib (NTB), was loaded into the biocompatible micelles. The expression of the efflux transporter was reversed by grafting quercetin. The peptide (glycylsarcosine, GS) was modified to target the influx transporter "Peptide Transporter-1" (PepT-1). Quercetin (QRT) and nintedanib (NTB) were transported to the cornea cooperatively, achieving long retention on the ocular surface and high compatibility. In a New Zealand rabbit model, within 8 hours after local administration, GSCQ@NTB was enriched in corneal stromal neovascularization and effectively inhibited the progress of neovascularization. Its effectiveness is slightly better than that in the first-line clinical application of steroids. In this study, we introduce the preparation of a dual adaptive nano-micelle system, which may provide an effective non-invasive treatment for corneal neovascularization.

Current targeting strategies and advanced nanoplatforms for atherosclerosis therapy.

Atherosclerosis is one of the major causes of death worldwide, and it is closely related to many cardiovascular diseases, such as stroke, myocardial infraction and angina. Although traditional surgical and pharmacological interventions can effectively retard or slow down the progression of atherosclerosis, it is very difficult to prevent or even reverse this disease. In recent years, with the rapid development of nanotechnology, various nanoagents have been designed and applied to different diseases including atherosclerosis. The unique atherosclerotic microenvironment with signature biological components allows nanoplatforms to distinguish atherosclerotic lesions from normal tissue and to approach plaques specifically. Based on the process of atherosclerotic plaque formation, this review summarises the nanodrug delivery strategies for atherosclerotic therapy, trying to provide help for researchers to understand the existing atherosclerosis management approaches as well as challenges and to reasonably design anti-atherosclerotic nanoplatforms.

Zwitterionic Injectable Hydrogel-Combined Chemo- and Immunotherapy Medicated by Monomolecular Micelles to Effectively Prevent the Recurrence of Tumor Post Operation.

Surgical resection remains the most common method of tumor treatment; however, the high recurrence and metastasis after surgery need to be solved urgently. Herein, we report an injectable zwitterionic hydrogel based on "thiol-ene" click chemistry containing doxorubicin (DOX) and a macrophage membrane (MM)-coated 1-methyl-tryptophan (1-MT)-loaded polyamide-amine dendrimer (P-DOX/1MT) for preventing the postoperative recurrence of tumors. The results indicated that P-DOX/1MT@MM exhibited enhanced recognition and uptake of the dendrimer by tumor cells and induced the immunogenic cell death. In the mice tumor model, the P-DOX/1MT@MM-Gel exhibited high therapeutic efficiency, which could significantly reduce the recurrence of the tumor, including suppressing tumor growth, promoting dendritic cell maturation, and increasing tumor-infiltrating cytotoxic T lymphocytes. The mechanism analysis revealed that the hydrogel greatly reduces the side effects to normal tissues and significantly improves its therapeutic effect. 1MT in the hydrogel is released more rapidly, improving the tumor suppressor microenvironment and increasing the tumor cell sensitivity to DOX. Then, the DOX in the P-DOX/1MT@MM effectively eliminatedo the residual tumor cells and exerted enhanced toxicity. In conclusion, this novel injectable hydrogel that combines chemotherapy and immunotherapy has the property of sequential drug release and is a promising strategy for preventing the postoperative recurrence of tumors.

The permeability of puerarin loaded poly(butylcyanoacrylate) nanoparticles coated with polysorbate 80 on the blood-brain barrier and its protective effect against cerebral ischemia/reperfusion injury.

Puerarin (PUE) is a good candidate for treating stroke, but its low concentration in brain after administration limits its curative efficacy. The aim of the present work was to design and characterize PUE loaded poly(butylcyanoacrylate) nanoparticles (PBCN) coated with polysorbate 80 (Ps 80), and to evaluate the effect of PBCN on the permeability of PUE across the blood-brain barrier (BBB) and the effect of PUE loaded PBCN on the cerebral ischemia/reperfusion injury. PUE loaded PBCN were successfully prepared by anionic polymerization method with the mean particle size of 201.2 nm and the zeta potential of -7.72 mV. The in vitro release behavior of PUE from the nanoparticles showed a biphasic profile manner with an initial burst release followed by a sustained release. The results of pharmacokinetic and biodistribution to brain performed in mice after intravenous administration showed that the drug concentrations in blood and brain for PUE loaded PBCN were both greater than these for the free drug. Moreover, compared with free drug, the vein injection of PUE loaded PBCN exerted the better neuroprotective effect in rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, lowing brain water content, and reducing the infarct volume. The results indicated that this preparation may reduce the total dose required for the stroke therapy with concurrent reduction in dose related toxicity. All these findings suggest that PBCN could enhance the transport of PUE to brain and have a potential as a neuroprotective agent in the focal cerebral ischemic injury.