Aminolysis-mediated single-step surface functionalization of poly (butyl cyanoacrylate) microbubbles for ultrasound molecular imaging.

Molecular ultrasound imaging with actively targeted microbubbles (MB) proved promising in preclinical studies but its clinical translation is limited. To achieve this, it is essential that the actively targeted MB can be produced with high batch-to-batch reproducibility with a controllable and defined number of binding ligands on the surface. In this regard, poly (n-butyl cyanoacrylate) (PBCA)-based polymeric MB have been used for US molecular imaging, however, ligand coupling was mostly done via hydrolysis and carbodiimide chemistry, which is a multi-step procedure with poor reproducibility and low MB yield. Herein, we developed a single-step coupling procedure resulting in high MB yields with minimal batch-to-batch variation. Actively targeted PBCA-MB were generated using an aminolysis protocol, wherein amine-containing cRGD was added to the MB using lithium methoxide as a catalyst. We confirmed the successful conjugation of cRGD on the MB surface, while preserving their structure and acoustic signal. Compared to the conventional hydrolysis protocol, aminolysis resulted in higher MB yields and better reproducibility of coupling efficiency. Optical imaging revealed that under flow conditions, cRGD- and rhodamine-labelled MB, generated by aminolysis, specifically bind to tumor necrosis factor-alpha (TNF-α) activated endothelial cells in vitro. Furthermore, US molecular imaging demonstrated a markedly higher binding of the cRGD-MB than of control MB in TNF-α activated mouse aortas and 4T1 tumors in mice. Thus, using the aminolysis based conjugation approach, important refinements on the production of cRGD-MB could be achieved that will facilitate the production of clinical-scale formulations with excellent binding and ultrasound imaging performance.

Polymerization Properties of n-Butyl Cyanoacrylate Mixed with Ethiodized Oil in the Lymphatic System: In Vivo Investigation in a Rabbit Model.

PURPOSE: To evaluate the polymerization properties of a mixture of n-butyl cyanoacrylate (nBCA) and ethiodized oil in the lymphatic system using an animal model. MATERIALS AND METHODS: Nineteen male Japanese White rabbits underwent 28 lymphatic embolization procedures under fluoroscopic guidance using manually injected mixtures of nBCA and ethiodized oil at ratios of 1:2 (nBCA density of 33%), 1:4 (20%), 1:6 (14%), and 1:8 (11%) via the popliteal lymph node. The time required for polymerization and the distance traveled by the mixture were evaluated and compared among the groups using the Kruskal-Wallis test. Histopathologic intergroup comparisons and time-course changes were also evaluated using embolized lymph nodes. RESULTS: Among 23 successful procedures, the mean polymerization times were 14 ± 3, 88 ± 93, 331 ± 292, and 932 seconds ± 540 and the mean distances traveled were 13 ± 10, 31 ± 44, 85 ± 89, and 108 mm ± 35 in the 33% (n = 5), 20% (n = 6), 14% (n = 6), and 11% (n = 6) groups, respectively. The 11% group demonstrated a significantly longer polymerization time than the 33%, 20%, and 14% groups and distance traveled than the 33% group. Pathologically, the embolized lymph nodes showed inflammatory changes and massive necrosis regardless of the nBCA density. CONCLUSIONS: Polymerization times and distances traveled were increased when nBCA was diluted with increasing quantitites of ethiodized oil in this rabbit model of lymphatic embolization. These relationships should be considered when dilution is prescribed for clinical use.

Poly(butyl cyanoacrylate) nanoparticles-deliveredß-nerve growth factor promotes the neurite outgrowth and reduces the mortality in the rat after traumatic brain injury.

Several transport vectors, including nanoparticles, have been reported to be used for the delivery of therapeutic medicines crossing the impermeable blood-brain barrier (BBB) to treat the diseases in the central nerve system (CNS), such as traumatic brain injury (TBI). Poly(n-butyl-2-cyanoacrylate) (PBCA) nanoparticles, made from biocompatible material, are regarded as a better potential delivery tool than others such as gold nanoparticles due to their degradabilityin vivo. However, little is known whether PBCA nanoparticles can be used to deliver neurotrophic factors into the brain to treat TBI. In this study, we first synthesized PBCA-carriedß-nerve growth factor, a neurotrophic agent with a large molecular weight, and then intravenously injected the compound into TBI rats. We found that despite undergoing several synthesis steps and host circulation,ß-NGF was able to be successfully delivered into the injured brain by PBCA nanoparticles, still maintain its neurotrophic activity for neurite outgrowth, and reduce the mortality of TBI rats. Our findings indicate that PBCA nanoparticles, with Tween 80, are an efficient delivery vector and a protective reservoir for large molecular therapeutic agents to treat TBI intravenously.

Design, Preparation, and Evaluation of Osthol Poly-Butyl-Cyanoacrylate Nanoparticles with Improved In Vitro Anticancer Activity in Neuroblastoma Treatment.

Osthol (osthole), known as a neuroprotective drug, has shown potent anticancer activity. However, the potential clinical application of osthol is limited due to its low water solubility and low bioavailability. Polybutyl cyanoacrylate (PBCA) has been widely used to improve the solubility of drugs with poor water solubility. In this study, an orthogonal experimental design (OED) was applied to design the preparation process of PBCA nanoparticles (NPs). Then, nanoparticles were prepared and evaluated in terms of physicochemical properties, in vitro release, and cellular uptake, etc. Further, the anti-cancer activity of osthol-PBCA NPs was demonstrated in SH-SY5Y cells. The pharmacokinetics and area under the curve (AUC) were investigated. The obtained osthol-NPs presented a spherical shape with a particle size of 110 ± 6.7 nm, a polydispersity index (PDI) of 0.126, and a zeta potential of −13 ± 0.32 mV. Compared with the free osthol, the drugs in osthol-NPs presented better stability and sustained release pattern activity. In vitro analysis using SH-SY5Y neuroblastoma cells showed that osthol-loaded nanoparticles displayed a significantly enhanced intracellular absorption process (three times) and cytotoxicity compared with free osthol (p < 0.05, increased 10−20%). The in vivo pharmacokinetic study revealed that the AUC of osthol-NPs was 3.3-fold higher than that of free osthol. In conclusion, osthol-PBCA NPs can enhance the bioactivity of osthol, being proposed as a novel, promising vehicle for drug delivery.

The Effect of Polybutylcyanoacrylate Nanoparticles as a Protos Delivery Vehicle on Dental Bone Formation.

BACKGROUND: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier "polybutylcyanoacrylate" (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. METHODOLOGY: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. RESULTS: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of -1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. CONCLUSION: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.

Drug Loading in Poly(butyl cyanoacrylate)-Based Polymeric Microbubbles.

Microbubbles (MB) are routinely used ultrasound (US) contrast agents that have recently attracted increasing attention as stimuli-responsive drug delivery systems. To better understand MB-based drug delivery, we studied the role of drug hydrophobicity and molecular weight on MB loading, shelf-life stability, US properties, and drug release. Eight model drugs, varying in hydrophobicity and molecular weight, were loaded into the shell of poly(butyl cyanoacrylate) (PBCA) MB. In the case of drugs with progesterone as a common structural backbone (i.e., for corticosteroids), loading capacity and drug release correlated well with hydrophobicity and molecular weight. Conversely, when employing drugs with no structural similarity (i.e., four different fluorescent dyes), loading capacity and release did not correlate with hydrophobicity and molecular weight. All model drug-loaded MB formulations could be equally efficiently destroyed upon exposure to US. Together, these findings provide valuable insights on how the physicochemical properties of (model) drug molecules affect their loading and retention in and US-induced release from polymeric MB, thereby facilitating the development of drug-loaded MB formulations for US-triggered drug delivery.

How Nanoparticle Physicochemical Parameters Affect Drug Delivery to Cells in the Retina via Systemic Interactions.

Minor changes in the composition of poloxamer 188-modified, DEAE-dextran-stabilized (PDD) polybutylcyanoacrylate (PBCA) nanoparticles (NPs), by altering the physicochemical parameters (such as size or surface charge), can substantially influence their delivery kinetics across the blood-retina barrier (BRB) in vivo. We now investigated the physicochemical mechanisms underlying these different behaviors of NP variations at biological barriers and their influence on the cellular and body distribution. Retinal whole mounts from rats injected in vivo with fluorescent PBCA NPs were processed for retina imaging ex vivo to obtain a detailed distribution of NPs with cellular resolution in retinal tissue. In line with previous in vivo imaging results, NPs with a larger size and medium surface charge accumulated more readily in brain tissue, and they could be more easily detected in retinal ganglion cells (RGCs), demonstrating the potential of these NPs for drug delivery into neurons. The biodistribution of the NPs revealed a higher accumulation of small-sized NPs in peripheral organs, which may reduce the passage of these particles into brain tissue via a "steal effect" mechanism. Thus, systemic interactions significantly determine the potential of NPs to deliver markers or drugs to the central nervous system (CNS). In this way, minor changes of NPs' physicochemical parameters can significantly impact their rate of brain/body biodistribution.

In Vitro Evaluation of the Polymerization Properties of N-Butyl Cyanoacrylate/Iodized Oil Mixtures for Lymphatic Interventions.

PURPOSE: To evaluate polymerization of N-butyl cyanoacrylate (NBCA)/iodized oil mixtures for lymphatic interventions in vitro. MATERIALS AND METHODS: Polymerization times of different NBCA/iodized oil mixtures (ratios of 1:0-1:7) were investigated in a static and dynamic experimental setup (performed in a lymph flow model in a silicone tube). Eight lymphatic samples with different triglyceride (TG) concentrations (low TGs, < 50 mg/dL; medium TGs, approximately 100-400 mg/dL; high TGs, > 700 mg/dL) were investigated. Morphologic changes during NBCA polymerization were monitored and recorded by video. Statistical analysis was performed with intergroup comparisons (Kruskal-Wallis test) and multiple regression analysis. RESULTS: Static experiments showed increasing polymerization times with increasing concentrations of iodized oil as well as increasing concentrations of TGs. In the low-TG group, polymerization time increased from 14 s at a 1:1 ratio of NBCA to iodized oil to 1,336 s at a 1:7 ratio; times in the medium-TG group increased from 21 s (1:1) to 2,546 s (1:7), and those in the high TG group increased from 168 s (1:1) to 16,530 s (1:7). In dynamic experiments, prolongation of polymerization time was less pronounced. For low- and medium-TG groups, total occlusion of the silicon tube was observed in all cases during the embolization procedure at between 26 seconds (1:1 ratio) and 52 seconds (1:7). In the high-TG group, polymerization took considerably longer (between 43 s [1:1] and 467 s [1:7]) or failed completely. CONCLUSIONS: Polymerization time of NBCA/iodized oil in lymph seems to be prolonged by increasing iodized oil and TG concentrations.

Clampless and sutureless laparoscopic partial nephrectomy using monopolar coagulation with or without N-butyl-2-cyanoacrylate.

OBJECTIVE: To describe a novel technique for clampless and sutureless laparoscopic partial nephrectomy (LPN) using monopolar coagulation with or without N-butyl-2-cyanoacrylate (NBCA). METHODS: From February 2015 to October 2018, we performed clampless and sutureless LPN using monopolar coagulation with or without NBCA on 142 patients. The tumors were resected with cold scissor. The tumor beds were repeatedly coagulated with a monopolar hook in spray and fulgurate modes. NBCA was sprayed when bleeding was observed after coagulation in 98 patients. We compared outcomes in the NBCA and non-NBCA groups. RESULTS: Mean patient age was 55 years (range 20-86). Mean tumor size was 3.2 cm (range 1.0-10.6). Mean RENAL nephrometry score was 5 (range 4-8). Mean operative time was 120 min (range 40-200). Mean estimated blood loss was 100 ml (range 10-500). Mean eGFR changes were 2.3 ml/min. Two patients had positive surgical margins. Three patients received blood transfusions. No patients had urine leakage. Patients receiving NBCA had larger tumors (3.0 vs 2.0 cm, p < 0.001), higher RENAL nephrometry scores (5.59 vs 4.47, p = 0.004), and higher E item scores (p = 0.009). CONCLUSIONS: Use of monopolar coagulation with NBCA in clampless and sutureless LPN for renal tumors with low RENAL nephrometry scores is safe and effective. For patients with exophytic renal tumors less than 2 cm, NBCA is not necessary.

Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved Properties as an Anticancer Agent.

This study aims to improve the cytotoxicity and potency of cisplatin-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) for the treatment of lung cancer through the modulation of temperature and polyethylene glycol (PEG) concentration as effective factors affecting the NPs' properties. The NPs were synthesized using an anionic polymerization method and were characterized in terms of size, drug loading efficiency, drug release profile, cytotoxicity effects, drug efficacy, and drug side effects. In this regard, dynamic light scattering (DLS), scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) methods, and hematoxylin and eosin (H&E) staining were used. The results showed that the size and the drug loading efficiency of the synthesized spherical NPs were 355­386 nm and 14­19%, respectively. Also, the drug release profile showed a controlled and slow drug release pattern with approximately 10% drug release over 48 h. In addition, the NPs significantly increased the cytotoxicity of the cisplatin in vitro environment by approximately 2 times and enhanced the therapeutic effects of the drug in vivo environment by increasing the survival time of lung-cancer-bearing mice by 20% compared to the standard drug receiver group. Also, the nanoformulation decreased the drug toxicity in an in vivo environment. According to the results, increasing the temperature and PEG concentration improved the properties of the drug loading efficiency, drug release profile, and cytotoxicity effect of drug-loaded NPs. Consequently, the synthesized formulation increased the survival of tumor-bearing mice and simultaneously decreased the cisplatin toxicity effects. In conclusion, the prepared nanoformulation can be considered a promising candidate for further evaluation for possible therapeutic use in the treatment of lung cancer.

Protective Effect of PBCA Nanoparticles Loaded with Thymulin Against the Relapsing-Remitting Form of Experimental Autoimmune Encephalomyelitis in Mice.

Relapsing-remitting experimental autoimmune encephalomyelitis (rEAE) in mice is a model that closely resembles relapsing-remitting multiple sclerosis in humans. This study aims to investigate a new approach to modulation of the inflammatory response in rEAE mice using a thymic peptide thymulin bound to polybutylcyanoacrylate (PBCA) nanoparticles. PBCA nanoparticles were used to prolong the presence of thymulin in the blood. Cytokine levels in blood were measured by ELISA; NF-κB and SAPK/JNK cascade activation, as well as Hsp72 and p53 protein expression, were measured by Western blotting. Animal health statuses were estimated using severity scores. Results showed that the cytokine response in rEAE was multi-staged: an early phase was accompanied by an increase in plasma interferon-γ, while the interleukin (IL)-17 response was markedly increased at a later stage. The stages were attributed to rEAE induction and maintenance phases. Thymulin significantly alleviated symptoms of rEAE and lowered plasma cytokine levels both in early and later stages of rEAE, and decreased NF-κB and SAPK/JNK cascade activation. Thymulin modulated NF-kappaB pathway activity via site-specific phosphorylation of RelA/p65 protein (at Ser276 and Ser536). The effect of nanoparticle-bound thymulin was more pronounced than the effect of free thymulin. Therefore, PBCA-thymulin can be considered a prospective treatment for this pathology.

Quantification and Qualitative Effects of Different PEGylations on Poly(butyl cyanoacrylate) Nanoparticles.

Protein adsorption on nanoparticles (NPs) used in nanomedicine leads to opsonization and activation of the complement system in blood, which substantially reduces the blood circulation time of NPs. The most commonly used method to avoid protein adsorption is to coat the NPs with polyethylene glycol, so-called PEGylation. Although PEGylation is of utmost importance for designing the in vivo behavior of the NP, there is still a considerable lack of methods for characterization and fundamental understanding related to the PEGylation of NPs. In this work we have studied four different poly(butyl cyanoacrylate) (PBCA) NPs, PEGylated with different types of PEG-based nonionic surfactants-Jeffamine M-2070, Brij L23, Kolliphor HS 15, Pluronic F68-or combinations thereof. We evaluated the PEGylation, both quantitatively by nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and time-of-flight secondary ion mass spectrometry (ToF-SIMS) and qualitatively by studying ζ-potential, protein adsorption, diffusion, cellular interactions, and blood circulation half-life. We found that NMR and ToF-SIMS are complementary methods, while TGA is less suitable to quantitate PEG on polymeric NPs. It was found that longer PEG increases both blood circulation time and diffusion of NPs in collagen gels.

Enhanced oral bioavailability of 10-hydroxycamptothecin through the use of poly (n-butyl cyanoacrylate) nanospheres.

The article describes the preparation, physicochemical characterization, drug release, and in vivo behavior of 10-hydroxycamptothecin-loaded poly (n-butyl cyanoacrylate) (PBCA) nanospheres (HCPT-PBCA-NSs). HCPT-PBCA-NSs were successfully prepared via emulsion polymerization of n-butyl cyanoacrylate (BCA) monomer in acidic medium with the aid of two colloidal stabilizers (Poloxamer 188 and Dextran 70). The influence of pH, the time of polymerization, and the dosage of the drug on particle size and encapsulation efficiency (EE) were studied. HCPT-PBCA-NSs were of spherical shape and uniformly dispersed with a particle size of 135.7 nm, and zeta potential of -18.18 mV. EE, drug loading (DL), and yield of HCPT-PBCA-NSs were 51.52, 0.63, and 88.25%, respectively. FTIR, 1H NMR, and DSC showed complete polymerization of BCA monomer and HCPT existed in the form of molecular or amorphous in NSs. In vitro release of the drug from HCPT-PBCA-NSs exhibited sustained-release behavior with an initial burst release and about 60% of HCPT was released from the formulation within 24 h of dialysis. The pharmacokinetic study in healthy rats after oral administration showed that encapsulation of HCPT into PBCA-NSs increased the Cmax about 3.84 times and increased AUC0-t about 5.40 times compared with that of HCPT suspension. It was concluded that PBCA-NSs could be a promising drug carrier to load HCPT for oral drug delivery if efforts are made in the future to improve its poor DL capacity.

Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells.

Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting. The HRE-cmvBDNF appeared to adsorb onto the surface of PS80 PBCA NC, with a resultant mean diameter of 92.6 ± 1.0 nm and zeta potential of -14.1 ± 1.1 mV. HIF-1α level in iPSCs was significantly higher in hypoxia, which resulted in a 51% greater BDNF expression when transfected with PS80 PBCA NC/HRE-cmvBDNF than those without hypoxia. TrkB and phospho-Akt were also elevated which correlated with neural differentiation. The findings suggest that PS80 PBCA NC too can be endocytosed to serve as an efficient vector for genes coupled to the HRE in hypoxia-sensitive cells, and activation of the PI3/Akt pathway in iPSCs by BDNF is capable of neural lineage specification.

Development and Characterization of Magnetite/Poly(butylcyanoacrylate) Nanoparticles for Magnetic Targeted Delivery of Cancer Drugs.

A great attention is presently paid to the design of drug delivery vehicles based on surface-modified magnetic nanoparticles. They can, in principle, be directed to a desired target area for releasing their drug payload, a process triggered by pH, temperature, radiation, or even magnetic field. To this, the possibility of forming part of diagnostic tools by enhanced magnetic resonance imaging or that of further treatment by magnetic hyperthermia can be added. Bare particles are rapidly eliminated from the bloodstream by the phagocyte mononuclear system, leading to short biological half-life. It is hence required to coat them in order to increase their biocompatibility and facilitate the drug incorporation. In this work, magnetite nanoparticles were coated with poly(butylcyanoacrylate) (PBCA) manufactured and characterized with regard to their physical properties and their suitability as a platform for magnetically controlled drug delivery. The average diameter of magnetite and core-shell nanoparticles was 97 ± 19 and 140 ± 20 nm, respectively. Infrared analysis, electrophoretic mobility, surface thermodynamics analysis, and X-ray diffraction all confirmed that the magnetic particles were sufficiently covered by the polymer in the composite nanoparticles. In addition, assays using normal (CCD-18 and MCF-10A) and tumoral (T-84 and MCF-7) cell lines derived from colon and breast tissue, respectively, demonstrated that nanocomposites have low or negligible cytotoxicity. It is concluded that PBCA-coated magnetite core-shell nanoparticles represent a remarkable promise as a platform for magnetically controlled drug delivery.

Embolization of Arteriovenous Malformations: Effect of Flow Control and Composition of n-Butyl-2 Cyanoacrylate and Iodized Oil Mixtures with and without Ethanol in an in Vitro Model.

Purpose To elucidate the effect of flow control (ie, balloon occlusion) and the composition of various mixtures of n-butyl-2 cyanoacrylate (NBCA) and iodized oil, with and without the addition of ethanol, for the treatment of arteriovenous malformations in an in vitro model. Materials and Methods A simulation circuit device that featured an artificial nidus was filled with heparinized swine blood obtained during exsanguination from another Institutional Animal Care and Use Committee-approved protocol and was constructed to generate pulsatile flow. Mixtures of NBCA and iodized oil (NL) at a 1:1 ratio (NL 1:1); NL and ethanol (NLE) at a 1:1:3 ratio (NLE 1:1:3) with or without flow control; and NL at 1:3, 1:5, and 1:10 ratios without flow control were injected six times each for a total of 42 trials. Embolization was classified as complete filling, proximal occlusion, pass through, or distal overpenetration after occlusion balloon deflation, and the trial results were compared. The results of the embolization test were evaluated by using the Fisher exact probability test to compare optimal and suboptimal embolization groups. Results NLE 1:1:3 with flow control completely filled the nidus in all six trials. NL 1:1 delivered with flow control achieved complete nidus filling in three of six injections, as did the NL 1:5 ratio trial without flow control. Complete embolization with NLE 1:1:3 with flow control was more feasible to achieve complete nidus filling than was NL 1:1 with flow control or NL 1:5 without flow control, although there was no statically significant difference (all, P = .09). None of the other mixtures produced complete embolization. Conclusion NLE 1:1:3 showed consistent and reproducible complete embolization with flow control and was stable after balloon deflation, making it an acceptable material for embolization in an in vitro arteriovenous malformation model. Further study should be performed before the NLE 1:1:3 mixture is used in routine clinical practice. (©) RSNA, 2015.

A Comparative Study of Orally Delivered PBCA and ApoE Coupled BSA Nanoparticles for Brain Targeting of Sumatriptan Succinate in Therapeutic Management of Migraine.

PURPOSE: The present investigation aimed at brain targeting of sumatriptan succinate (SS) for its optimal therapeutic effect in migraine through nanoparticulate drug delivery system using poly (butyl cyanoacrylate) (PBCA) and bovine serum albumin linked with apolipoprotein E3 (BSA-ApoE). METHOD: The study involved formulation optimization of PBCA nanoparticles (NPs) using central composite design for achieving minimum particle size, maximum entrapment efficiency along with sustained drug release. SS incorporated in BSA-ApoE NPs (S-AA-NP) were prepared by desolvation technique and compared with SS loaded polysorbate 80 coated optimized PBCA NPs (FPopt) in terms of their brain uptake potential, upon oral administration in male Wistar rats. The NPs were characterized by FTIR, thermal, powder XRD and TEM analysis. RESULTS: The in vivo studies of FPopt and S-AA-NP on male Wistar rats demonstrated a fairly high brain/plasma drug ratio of 9.45 and 12.67 respectively 2 h post oral drug administration. The behavioural studies on male Swiss albino mice affirmed the enhanced anti-migraine potential of S-AA-NP than FPopt (P < 0.001). CONCLUSION: The results of this work, therefore, indicate that BSA-ApoE NPs are significantly better than polysorbate 80 coated PBCA NPs for brain targeting of SS (P < 0.05) and also offer an improved therapeutic strategy for migraine management.

Bacteriolysis by vancomycin-conjugated acryl nanoparticles and morphological component analysis.

Nanoparticles are currently attracting considerable attention because of their ability to conjugate to various substances. As such, these nanoparticles can assist the transfer of the conjugated substance to target tissues where they are gradually released. In this study, vancomycin-conjugated nanoparticles (VCM NPs) were prepared. The antibacterial activity of VCM NPs was compared with that of VCM alone by exposure to vancomycin-resistant enterococci (VRE). The morphology of the cells was then analyzed by electron microscopy. VCM NPs were found to have more potent antibacterial activity against VRE compared to VCM alone, but the activity against vancomycin-sensitive enterococci (VSE) remained the same. The antibacterial activity of nanoparticles alone was the same against VSE and VRE. The nanoparticles were found to induce characteristic morphological changes in the bacteria based on scanning and transmission electron microscopy. The results suggest that the strong antibacterial activity of VCM NPs against VRE may be attributable not only to the well-known control release carrier property of the nanoparticles but to an additional mechanism that involves VCM NPs avoiding the drug resistant mechanism of VRE.

Perfluorodecalin-soluble fluorescent dyes for the monitoring of circulating nanocapsules with intravital fluorescence microscopy.

Perfluorodecalin (PFD) is an established artificial oxygen carrier due to its physical capability to solve the respiratory gases oxygen and carbon dioxide. PFD-filled poly(n-butyl-cyanoacrylate) (PACA) nanocapsules are already discussed as effective artificial oxygen carriers, and their principal suitability for intravenous administration had been shown. To further elucidate their action in vivo, it is imperative to characterise their preclinical safety and particularly their biodistribution. For these purposes, intravital fluorescence microscopy would display an attractive technique in order to monitor the PACA nanocapsules in vivo, but unfortunately, it is impossible to stain the PACA nanocapsules with a fluorescent dye fulfilling special criteria required for in vivo microscopy. In order to develop such a dye, a long-chained fluorinated thiol was used to modify a BODIPY derivative that is a highly fluorescent organic compound belonging to the difluoro-boraindacene family, as well as to functionalise mesoscopic systems, such as CdSe/ZnS-quantum dots and gold nanoparticles. Furthermore, a functionalisation of porphyrin derivatives was investigated by placing divalent ions in the centre of these systems. Due to the high solubility of all synthesised dyes in PFD, it should be possible to stain PFD-filled particles in general. However, only the functionalised BODIPY derivative was suitable for in vivo monitoring of the PFD-filled PACA nanocapsules.

n-Butyl cyanoacrylate synthesis. A new quality step using microwaves.

Alkyl cyanoacrylates are interesting products for use in industry because of their properties enabling them to stick together a wide range of substrates. n-Butyl cyanoacrylate is one of the most successfully used tissue adhesives in the field of medicine because it exhibits bacteriostatic and haemostatic characteristics, in addition to its adhesive properties. At present, its synthesis is performed with good yields via Knoevenagel condensation using conventional sources of heating, but this requires a long processing time. The aim of this work was to look for a new way of synthesising n-butyl cyanoacrylate using microwave irradiation as the source of heating. This non-conventional source of heating most likely reduces the process time of the synthesis. In comparison with a conventional heating source, such as an oil bath, the results showed the advantages of this method whereby the n-butyl cyanoacrylate gave the same yield and quality with a reduction in the reaction time by a factor of 3-5-fold.