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Brain cancer is the most aggressive one among various cancers. It has a drastic impact on people's lives because of the failure in treatment efficacy of the currently employed strategies. Various strategies used to relieve pain in brain cancer patients and to prolong survival time include radiotherapy, chemotherapy, and surgery. Nevertheless, several inevitable limitations are accompanied by such treatments due to unsatisfactory curative effects. Generally, the treatment of cancers is very challenging due to many reasons including drugs' intrinsic factors and physiological barriers. Blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) are the two additional hurdles in the way of therapeutic agents to brain tumors delivery. Combinatorial and targeted therapies specifically in cancer show a very promising role where nanocarriers' based formulations are designed primarily to achieve tumor-specific drug release. A dual-targeting strategy is a versatile way of chemotherapeutics delivery to brain tumors that gets the aid of combined ligands and mediators that cross the BBB and reaches the target site efficiently. In contrast to single targeting where one receptor or mediator is targeted, the dual-targeting strategy is expected to produce a multiple-fold increase in therapeutic efficacy for cancer therapy, especially in brain tumors. In a nutshell, a dual-targeting strategy for brain tumors enhances the delivery efficiency of chemotherapeutic agents via penetration across the blood-brain barrier and enhances the targeting of tumor cells. This review article highlights the ongoing status of the brain tumor therapy enhanced by nanoparticle based delivery with the aid of dual-targeting strategies. The future perspectives in this regard have also been highlighted.

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Commercially available protein reference standard materials are widely used for the quantitation of intact proteins in biopharmaceuticals, food, and consumer products. However, the purity of protein reference standard materials are often assumed to be 100% or they may be assigned an inaccurate value because the methods used to determine protein purity often lack specificity and accuracy. In this study, a high performance liquid chromatography system equipped with a charged aerosol detector (HPLC-CAD) was used for universal response detection to provide a practical, specific, accurate, and robust method for the determination of the purity of protein reference standard materials. This work demonstrates the near uniform CAD responses for six proteins with different molecular weights and different structures. Flow injection analysis (FIA) was used to compare protein responses under various mobile phase and diluent compositions. Similar CAD responses for all six proteins were observed when the mobile phase composition included trifluoroacetic acid (TFA) and acetonitrile. These are typical conditions regularly applied to the separation of proteins by reversed phase (RP) chromatography. The universal response feature of the CAD was employed to determine the purity of Bowman-Birk inhibitor (BBI) reference standard material. This protein is an important ingredient in soybean products and has various therapy applications. Three major components were observed in the commercially available reference standard material by reversed phase gradient HPLC, BBI-Native, BBI-Isoform 1, and BBI-Isoform 2 at relative compositions of 60.0%, 34.2%, and 5.8%, respectively.

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A body-of-revolution finite-difference time-domain (BOR-FDTD) method was developed and employed to rigorously analyze axisymmetric transformation optics (TO) lenses. The novelty of the proposed BOR-FDTD technique is that analytical expressions were derived and presented to introduce obliquely incident plane waves into the total-field/scattered-field formulation, allowing for accurate simulation of BOR objects in layered media illuminated by obliquely incident waves. The accuracy of the proposed method was verified by comparing numerical results with analytical solutions. The developed code was further utilized to study the imaging properties of a cylindrical TO Luneburg lens on a substrate, demonstrating the desired focusing of light onto a flat plane.

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Identification and determination of leachable components are essential for the safety assessment of implantable medical devices. The safety concern threshold (SCT) for leachable components is 0.15 µg/day for genotoxic or carcinogenic compounds and 1.5 µg/day for others. Regulatory agencies require extraction of a whole medical device using an extraction media that simulates in vitro conditions. Large-sized medical devices therefore require large volumes of aqueous media, leading to extracts of very low concentrations of the targeted analytes. Analysis of these dilute solutions is often challenging, and pre-concentration steps are time consuming and can cause significant sample loss. Stir bar sorptive extraction (SBSE) has proven to be a very useful sample preparation technique that is simple and uses no (or minimal (<1 ml)) aqueous or organic solvents. When combined with a highly selective and sensitive GC-MS/MS analysis, volatile and semi-volatile leachable components can be determined at levels below the SCT of 150 ng/device. An SBSE-GC-MS/MS method using multiple reaction monitoring detection was validated for determination of antioxidant related leachable breakdown products from orthopedic knee-inserts made from ultra high molecular weight polyethylene.

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A molecular imaging application was developed to characterize the drug distribution on CYPHER® and NEVO™ Drug-eluting Stents using MALDI Qq-ToF analytical methodology. The coating matrix, laser energy, laser frequency, spatial resolution (related to rastering speed) and mass spectrometer parameters were optimized to analyze drug distribution in both durable and biodegradable polymer matrices. The developed method was extended to generate data from stents explanted from porcine coronary arteries. Due to the method's intrinsic specificity, it offers a significant advantage over other techniques in that it allows low-level detection of the target molecule without biological interferences from the blood or tissue. The method is also capable of detecting drug-related degradation products both from the finished stent product and from explanted stents.

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We present a detailed comparison of surface-enhanced Raman spectroscopy (SERS) signals from metallic nanoparticle arrays and their complementary hole arrays. Using an analytical model for local field enhancement, we show that the SERS enhancements of the hole arrays are closely related to their transmission spectra. This trend is experimentally confirmed and characterized by a cos(4 )θ dependence of the SERS signal on the excitation polarization angle θ. The particle arrays, on the other hand, exhibit quite different behavior because of the existence of considerable evanescent modes in the near field. Their maximal local field gains appear at wavelengths generally much larger than their localized surface plasmonic resonant wavelengths.

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Polyethersulfone (PES) hollow fibers were fabricated by dry-wet spinning method for hemodialysis application. The effects of additives polyethylene glycols (PEG) in the dope solution and of fiber thickness and inner diameter fiber on the membrane mechanical characters were investigated. The dialysis tests were conducted by using a simulated solution prepared by dissolving bovine serum albumin (BSA), lysozyme and urea in de-ionized water to test the effects of membrane characters and operating conditions on dialysis efficiency. The results indicated that the reduction of PEG concentration from 27.6 wt% to 24.1 wt% in the dope solution improved the clearance of toxins, but slightly decreased the mechanical characters. The reduction of fiber thickness or fiber inner diameter was found to improve the clearance of toxins by removing 64.2% of lysozyme and 89.4% of urea (membrane area 0.2 m2), whilst BSA retention was found being maintained above 98%. The dialysis efficiency was also noted to increase with the increase in the flow rate of either the simulated or the dialysate solution, or increasing the membrane area. Moreover, The result of a comparison on the clearance of toxins between commercial F60S and PES dialyzers indicated higher dialysis efficiency per area of the fabricated PES membrane.

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A near-infrared metamaterial design that is reconfigurable between almost completely transmissive and reflective states is presented. The reconfiguration is enabled by tuning the anisotropic nematic liquid crystals used as a spacer layer between two silver nanoplates in a planar doubly periodic metamaterial. The design is optimized for maximum difference in transmittance between the two states by using a genetic algorithm. For a linearly polarized illumination at normal incidence, full-wave electromagnetic analysis predicts that the optimized metamaterial film can change the transmittance between 98.7% and 0.1% at a wavelength of 1.1 microm.

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A case study was conducted to determine the relative response factors (RRFs) of paclitaxel-related impurities by high performance liquid chromatography (HPLC) equipped with an ultraviolet (UV) detector and charged aerosol detector (CAD) in tandem. The peak response using CAD was independent of analyte structure in an isocratic analysis for this application. After a sample containing known and unknown impurities was analyzed with HPLC-UV-CAD, an empirical approach was developed to calculate the RRFs for all impurities. The RRFs of known impurities were also determined by linear calibration curves. For known impurities, the RRFs values determined with two approaches are comparable. The new approach is effective yet simpler to determine the RRFs for unknown impurities or degradation products since the need for obtaining authentic pure materials was eliminated.

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A hydrophilic interaction chromatography (HILIC) method has been developed and validated as a secondary or orthogonal method complementary to a reversed-phase HPLC (RP-HPLC) method for quantitation of a polar active pharmaceutical ingredient and its three degradation products. The HILIC method uses a diol column and a mobile phase consisting of acetonitrile/water and ammonium chloride. The compounds of interest show significant differences in retention behaviors with the two very different chromatographic systems, which are desired in developing orthogonal methods. The HILIC method is validated and has met all validation acceptance criteria for the support of drug development activities.

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