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Qualitative and Quantitative Medical diagnosis in Head and Neck Cancer.
We succeeded in enhancing CTL activity by the CWS-NPs, and the findings reported herein should provide important information regarding target cells for the development of CWS-NP. We conducted a stability study of biodegradable and amphiphilic nanoparticles (NPs) consisting of phenylalanine attached poly(γ-glutamic acid) (γ-PGA-Phe) for drug delivery to find the optimal formulation, and define the optimal storage conditions using novel quantitative analytical methods. The stability of NP suspension and lyophilized NP powder manufactured by a dimethyl sulfoxide (DMSO)-based and an ethanol (EtOH)-based process was assessed under 5°C, 25°C/60% relative humidity (RH) and 40°C/75%RH. The content of γ-PGA-Phe, impurities, absolute molecular weight, appearance, clarity of solution, particle size, zeta potential, particle matter, osmolality, water content and pH were evaluated as parameters of NP stability. Lyophilized NPs with trehalose showed better stability. The lyophilized NP formulation could therefore provide a stable and high quality product for clinical studies and shows promise as an effective drug delivery system carrier. The cardiotoxicity of prospective impurities contained in NPs and reagents used in the manufacturing process with human induced pluripotent stem cells (hiPSC) derived three-dimensional (3D)-cardiomyocyte (CM) tissues by centrifugation Layer-by-Layer technique (LbL) was also evaluated. As a result, cardiotoxicity for NPs and reagents was not observed and it was clarified that the potential risk to human safety from NPs is low. The applicability of the approaches with hiPSC derived 3D-CM tissues by centrifugation LbL is will be evaluated. Albendazole (ABZ) and mebendazole (MBZ) are the 2 most commonly used drugs in the treatment of soil-transmitted helminth infections in humans, but their performance is hampered by low solubility and physicochemical properties. selleck chemicals We developed different formulations (β-cyclodextrin inclusion complexes, chitosan-based microcrystals (CH), and polyvinyl alcohol and polysorbate 80-based nanoparticles [P80]) of ABZ and MBZ with an improved in vitro solubility profile and tested their activities in vitro and in vivo against the hookworm Heligmosomoides polygyrus. We found that all formulations tested showed a faster and higher dissolution level and were more active than the standard drugs. When compared to ABZ, ABZ-P80 revealed the highest improvement in terms of solubility increase (4-fold increase) and in vivo activity (an ED50 of 7.0 mg/kg for ABZ and of 4.1 mg/kg for ABZ-P80). Although the activity of MBZ was in all cases lower than ABZ, the improved formulations of MBZ performed better than standard MBZ, where MBZ-CH showed a significantly higher in vivo activity (ED50 of 8.02 mg/kg vs. an ED50 of 203 mg/kg for MBZ). In this work, we identified MBZ-CH and ABZ-P80 formulations as lead formulations hence further studies should be conducted. Cutaneous leishmaniasis is a neglected tropical disease caused by the parasite Leishmania and transmitted by sandflies. It has become a major health problem in many tropical and subtropical countries, especially in regions of conflict and political instability. Currently, there are only limited drug treatments and no available licensed vaccine; thus, the need for more therapeutic interventions remains urgent. Previously, a DNA vaccine encoding a 15 kDa sandfly (Phlebotomus papatasi) salivary protein (PpSP15) and recombinant nonpathogenic Leishmania tarentolae secreting PpSP15 have been shown to induce protective immunity against Leishmania major in mice, demonstrating that PpSP15 is a promising vaccine candidate. In this study, we developed a fermentation process in yeast with a yield of ~1g PpSP15/L and a scalable purification process consisting of only 2 chromatographic purification steps with high binding capacity for PpSP15, suggesting that PpSP15 can be produced economically. The biophysical/biochemical analysis of the purified PpSP15 indicated that the protein was of high purity (>97%) and conformationally stable between pH 4.4 and 9.0. More importantly, the recombinant protein had a defined structure similar to that of the related PdSP15 from Phlebotomus duboscqi, implying the suitability of the yeast expression system for producing a correctly folded PpSP15. Currently, conjunctivitis is treated by frequent high dose administration of sparfloxacin eye drop solution. However, the eye drops are inconvenient because of low bioavailability, short ocular drug residence time, and need of frequent instillation, which lead to patient noncompliance affecting the routine life style of patients. Silicone contact lenses can be used to sustain the release of sparfloxacin. However, the presence of sparfloxacin alters the optical and physical properties of the contact lens. To overcome the issues, a novel polyvinyl pyrrolidone (PVP)-coated sparfloxacin-laden ring contact lens was designed to provide sustained ocular drug delivery without altering the optical and swelling properties of contact lens. The ring was implanted within the periphery of the lens. Sparfloxacin was loaded by soaking (Sp-S), direct loading (Sp-L), and ring casting method (Sp-R). PVP (comfort agent) was coated on the surface of contact lens by novel short surface curing technique. The in vitro sparfloxacin release data of Sp-S (up to 12-36 h) and Sp-L batches (up to 12-24 h) showed high burst release, whereas Sp-R batch showed sustained release up to 36-48 h without significant (p > 0.05) alteration of the optical and swelling properties. All the batches showed sustained release of PVP up to 48 h. The in vivo release studies in the rabbit tear fluid showed improvement in the sparfloxacin [>MIC for Staphylococcus aureus] and PVP retention time in comparison to eye drop solution. The in vivo efficacy study in the S aureus-induced conjunctivitis showed improved healing effect with the single PVP-coated Sp-R-300 contact lens in comparison to the frequent high-dose sparfloxacin eye drop therapy. The study demonstrated the successful application to codeliver sparfloxacin and PVP from the contact lens for the extended period to treat conjunctivitis.
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