Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

Self-assembling peptides (SAPs) are promising vehicles for the delivery of hydrophobic therapeutics for clinical applications; their amphipathic ...

University Health Network

Biological effects of Tat cell-penetrating peptide: a multifunctional Trojan horse?

A reconfigurable telecentric imaging system that can simultaneously capture multispectral and multi-polarization information in a single snapshot is demonstrated. The proposed design utilizes a telecentric imaging objective and a light pipe for image multiplexing. An array of filters is used to filter each of the multiplexed images at an intermediate image plane. In this paper, we will discuss the system configuration and present the experimental results.

Snapshot, reconfigurable multispectral and multi-polarization telecentric imaging system.

Near-infrared (NIR) fluorescence imaging systems have been developed for image guided surgery in recent years. However, current systems are typically bulky and work only when surgical light in the operating room (OR) is off. We propose a single camera imaging system that is capable of capturing NIR fluorescence and color images under normal surgical lighting illumination. Using a new RGB-NIR sensor and synchronized NIR excitation illumination, we have demonstrated that the system can acquire both color information and fluorescence signal with high sensitivity under normal surgical lighting illumination. The experimental results show that ICG sample with concentration of 0.13 μM can be detected when the excitation irradiance is 3.92 mW/cm(2) at an exposure time of 10 ms.

Single camera imaging system for color and near-infrared fluorescence image guided surgery.

A comprehensive charge-coupled device (CCD) camera noise model is employed to study the impact of CCD camera signal-to-noise ratio (SNR) on polarimetric accuracy. The study shows that the standard deviations of the measured degree of linear polarization (DoLP) and angle of linear polarization (AoLP) are mainly dependent on the camera SNR. With increase in the camera SNR, both the measurement errors and the standard deviations caused by the CCD camera noise decrease. When the DoLP of the incident light is smaller than 0.1, the camera SNR should be at least 75 to achieve a measurement error of less than 0.01. When the input DoLP is larger than 0.5, a SNR of 15 is sufficient to achieve the same measurement accuracy. An experiment is carried out to verify the simulation results.

Impact of CCD camera SNR on polarimetric accuracy.

A method to design one-dimensional beam-spitting phase gratings with low sensitivity to fabrication errors is described. The method optimizes the phase function of a grating by minimizing the integrated variance of the energy of each output beam over a range of fabrication errors. Numerical results for three 1x9 beam splitting phase gratings are given. Two optimized gratings with low sensitivity to fabrication errors were compared with a grating designed for optimal efficiency. These three gratings were fabricated using gray-scale photolithography. The standard deviation of the 9 outgoing beam energies in the optimized gratings were 2.3 and 3.4 times lower than the optimal efficiency grating.

Sensitivity analysis and optimization method for the fabrication of one-dimensional beam-splitting phase gratings.

A novel gold nanoparticle-peptide hybrid strategy was developed to intracellularly deliver a potent PKCδ inhibitor peptide for the treatment of acute lung injury. The gold nanoparticle-peptide hybrids showed good stability with high uptake, and demonstrated in vitro and in vivo efficacy. Our formulation strategy shows great promise in intracellular delivery of peptides.

Effective delivery of a rationally designed intracellular peptide drug with gold nanoparticle-peptide hybrids.

Achromatic beam-splitting grating doublets are designed for both continuous phase and binary phase gratings. By analyzing the sensitivity to lateral shifts between the two grating layers, it is shown that continuous-profile grating doublets are extremely difficult to fabricate. Achromatic grating doublets that have profiles with a constant first spatial derivative are significantly more resistant to lateral shifts between grating layers, where one design case showed a 17 times improvement in performance. Therefore, binary phase, multi-level phase, and blazed grating doublets perform significantly better than continuous phase grating doublets in the presence of a lateral shift between two grating layers. By studying the sensitivity to fabrication errors in the height of both grating layers, one grating layer height can be adjusted to maintain excellent performance over a large wavelength range if the other grating layer is fabricated incorrectly. It is shown in one design case that the performance of an achromatic Dammann grating doublet can be improved by a factor of 215 if the heights of the grating layers are chosen to minimize the performance change in the presence of fabrication errors.

Analysis of grating doublets for achromatic beam-splitting.

This Letter explores Fourier ptychography (FP) using epi-illumination. The approach effectively modifies the FP transfer function to be coherent-like out to the incoherent limit of twice the numerical aperture over the wavelength 2NA/λ. Images reconstructed using this approach are shown to have higher contrast at finer details compared with images using incoherent illumination, indicating that the FP transfer function is superior in high spatial frequency regions.

Transfer function analysis in epi-illumination Fourier ptychography.

In this Letter, the focal spot areas of an azimuthally polarized beam modulated with a vortex-0-2π-phase plate or a π-phase-step plate are numerically found to be smaller than a radially polarized beam for three pupil functions with uniform, Gaussian, and Bessel-Gauss profiles. Several types of multizone phase plates are theoretically designed and numerically simulated for generating tight multifocal arrays from the azimuthally polarized beams for what we believe is the first time. The positions and polarization states of the multifocal arrays can be controlled simply by varying the pattern of the multizone plates. The produced multifocal array with controllable position and polarization is beneficial to parallel optical recording and parallel optical imaging.

Generation of a controllable multifocal array from a modulated azimuthally polarized beam.

The Fourier ptychography technique in reflection mode has great potential applications in tissue imaging and optical inspection, but the current configuration either has a limitation on cut-off frequency or is not practical. By placing the imaging aperture stop outside the illumination path, the illumination numerical aperture (NA) can be greater than the imaging NA of the objective lens. Thus, the cut-off frequency achieved in the proposed optical system is greater than twice the objective's NA divided by the wavelength (2NAobj/λ ), which is the diffraction limit for the cut-off frequency in an incoherent epi-illumination configuration. We experimentally demonstrated that the synthesized NA is increased by a factor of 4.5 using the proposed optical concept. The key advantage of the proposed system is that it can achieve high-resolution imaging over a large field of view with a simple objective. It will have a great potential for applications in endoscopy, biomedical imaging, surface metrology, and industrial inspection.

Reflective Fourier ptychography.

Clinical application of hydrophobic therapeutics is restricted by lack of an efficient vehicle which permits their solubility in aqueous environments. We have previously developed a novel formulation strategy to deliver a hydrophobic Src inhibitor, PP2, involving combinations of one self-assembling peptide (SAP) and one of 4 selected amino acids (AAs). The present study aims to develop a generalized drug delivery platform for intravenous application of hydrophobic drugs by combining self-assembling peptide, amino acid and low concentration of co-solvent. A multi-step screening pipeline is established which includes assessment of drug solubility and physicochemical characteristics, as well as functional efficacy and safety in vitro and in vivo. Using PP2 as an exemplary hydrophobic compound, 480 different combinations of 6 SAPs, 20 naturally existing AAs at 2 concentrations, and 2 co-solvents were evaluated. Among the combinations, 60 formulae dissolved PP2; 10 of which significantly reduced thrombin-induced IL-8 production, a sign of inflammatory response, in normal human lung epithelial BEAS2B cells. These formulations did not show cytotoxicity alone, but 2 reduced cell viability with presence of thrombin. We then performed a double-blinded test in a rat model of pulmonary ischemia-reperfusion. PP2 formulated with EAK16-I peptide plus methionine and 2% ethanol were administrated intravenously, significantly reducing severity of lung injury. The SAP-AA formulation strategy was also successfully applied to other hydrophobic compounds, suggesting this strategy could be applicable to other hydrophobics for a variety of clinical applications.

Formulation of hydrophobic therapeutics with self-assembling peptide and amino acid: A new platform for intravenous drug delivery.

In this paper, the design and experimental demonstration of a snapshot linear-Stokes imaging spectropolarimeter (SLSIS) is presented. The SLSIS, which is based on division-of-focal-plane polarimetry with four parallel linear polarization channels and integral field spectroscopy with numerous slit dispersive paths, has no moving parts and provides video-rate Stokes-vector hyperspectral datacubes. It does not need any scanning in the spectral, spatial or polarization dimension and offers significant advantages of rapid reconstruction without heavy computation during post-processing. The principle and the experimental setup of the SLSIS are described in detail. The image registration, Stokes spectral reconstruction and calibration procedures are included, and the system is validated using measurements of tungsten light and a static scene. The SLSIS's snapshot ability to resolve polarization spectral signatures is demonstrated using measurements of a dynamic scene.

Shaun Pacheco

Latner Thoracic Surgery Research Laboratories

University Health Network

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

Shaun Pacheco

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University Health Network

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

Latner Thoracic Surgery Research Laboratories