Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. 1992 55(4):414–23.Ĭhauhan VP, Stylianopoulos T, Martin JD, Popovic Z, Chen O, Kamoun WS, et al. 1H- and 13C-nmr assignments for taxol, 7-epi-taxol, and cephalomannine. 1958 29(8):688–91.Ĭhmurny GN, Hilton BD, Brobst S, Look SA, Witherup KM, Beutler JA. Modified spin-echo method for measuring nuclear relaxation times.
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Effects of diffusion on free precession in nuclear magnetic resonance experiments. Solubility and stability of taxol: effects of buffers and cyclodextrins. Quantitation and characterization of process impurities and extractables in protein-containing solutions using proton NMR as a general tool. Nuclear magnetic resonance studies of the binding of captopril and penicillamine by serum albumin. Keire DA, Mariappan SV, Peng J, Rabenstein DL. Exploring the binding interaction mechanism of taxol in beta-tubulin and bovine serum albumin: a biophysical approach. Karthikeyan S, Bharanidharan G, Ragavan S, Kandasamy S, Chinnathambi S, Udayakumar K, et al.
High affinity binding of paclitaxel to human serum albumin. Interaction of taxol with human serum albumin. Human serum albumin nanoparticles for use in cancer drug delivery: process optimization and in vitro characterization. Lomis N, Westfall S, Farahdel L, Malhotra M, Shum-Tim D, Prakash S. Paclitaxel nano-delivery systems: a comprehensive review. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. Albumin-bound paclitaxel: a next-generation taxane. nab-Paclitaxel mechanisms of action and delivery. Collectively, the dilution-based NMR method offered an analytical approach to investigate physicochemical attributes of complex injectable products with minimal needed sample preparation and perturbation to nanoparticle formulation. In addition, 2D diffusion ordered NMR spectroscopy (DOSY) results revealed that the released paclitaxel experiencing slightly slowed diffusion rates than free paclitaxel, which was attributed to paclitaxel in equilibrium with albumin-bound states. The critical concentration of the drug product (DP) at 50% of release was 0.63 ± 0.04 mg/mL in PBS buffer.
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The non-invasive nature of NMR allows for precise measurement of a full range of dilution-induced drug release percentage from 14 to 92% without any sample extraction. Herein, solution NMR spectroscopy with a T 2-filtering technique was developed to detect paclitaxel signal while suppressing albumin signals to follow the released paclitaxel in the NMR tube upon dilution. However, because the higher-order nanostructures may affect the paclitaxel release, a suitable in vitro assay to detect potential differences in paclitaxel release between comparator lots and products is desirable. The molecular interaction between paclitaxel and albumin within the higher-order nanostructure is analytically challenging to assess, as is any correlation of differences to differences in therapeutic effect. The paclitaxel protein-bound particles for injectable suspension (marketed under the brand name Abraxane®) contains nanosized complexes of paclitaxel and albumin.
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