This study aimed to prepare edible films with cassava starch (CS) and sodium carboxymethyl cellulose (CMC) as basic raw materials and apple polyphenol (AP) as biologically active components. The addition of AP makes the flexibility of the film increase first and then decrease while the tensile strength decreases slightly and the barrier ability increases significantly. When the AP concentration was 70 mg/mL, the tensile strength of the film decreased from 5.61 ± 0.45 to 3.36 ± 0.19, the water vapor transmittance decreased from 7.17 ± 0.17 to 4.97 ± 0.07 and the peroxide value decreased from 1.896 ± 0.04 to 0.53 ± 0.04. By studying the microstructure of CS/CMC/AP-4 film, it was found that hydrogen bonds were formed between AP, CS, and CMC, and they showed high compatibility, thus improving the crystallinity. On this basis, the roughness of the film decreases and the compactness is enhanced. The increase in compactness is directly related to the increase in blocking ability. At the same time, the improvement of thermal stability is attributed to the increase in crystallinity. In addition, the application of CS/CMC/AP-4 film in chicken preservation also proved its antioxidant potential.

2019-04-01·Journal of Pharmaceutical Sciences3区 · 医学

Anisamido-Polyethylenimines as Efficient Nonviral Vectors for the Transport of Plasmid DNA to Sigma Receptor–Bearing Cells In Vitro

3区 · 医学

Article

作者: Ashwani Kumar Sharma ; Charu Garg ; Pradeep Kumar ; Alka Gupta

Site-specific delivery of therapeutics promises better outcomes in the treatment of diseases. A small ligand, anisamide, has been shown to specifically bind sigma receptors highly overexpressed on prostate cancer cells, one of the leading cancers causing deaths worldwide. Here, anisamide-tethered polyethylenimine polymers (AP) have been synthesized and evaluated for their capability to transport nucleic acid across the cell membrane. A series of modified polymers (AP-1 to AP-4) was synthesized, physicochemically characterized, and evaluated for their transfection efficiency and cytotoxicity. Postconjugation, there was a marginal decrease in the buffering capacity; however, it did not diminish the ultimate objective of the study rather improved the transfection efficiency and decreased the cytotoxicity making these polymers as efficient and safe vectors for nucleic acid delivery. All the modified polymers displayed enhanced capability to deliver DNA inside the cells. Among the series, the modified polymer, AP-4 (10% attempted substitution), exhibited the highest transfection in HEK293 cells having abundant sigma receptors with minimal cytotoxicity. The projected polymer also showed complete protection of bound DNA against enzymatic degradation. Altogether, the results demonstrated targeting ability of the proposed polymers to deliver nucleic acid to sigma receptor-bearing cells in vitro.

2018-07-01·Neuropharmacology2区 · 医学

Bioisosteres of ethyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo [1,5-a][1,4]diazepine-3-carboxylate (HZ-166) as novel alpha 2,3 selective potentiators of GABAA receptors: Improved bioavailability enhances anticonvulsant efficacy

2区 · 医学

Article

作者: Alatorre, A I ; Li, G ; Poe, M M ; Methuku, K R ; Smith, J L ; Siemian, J N ; Fisher, J L ; Gleason, S D ; Witkin, J M ; Krambis, M J ; Jin, X ; Crawford, J ; Schkeryantz, J M ; McDermott, J S ; Airey, D C ; Ping, X ; Cook, J M ; Jones, T M ; Tiruveedhula, V V N P B ; Cramer, J W ; Hobbs, J ; Cerne, R

HZ-166 has previously been characterized as an α2,3-selective GABA_A receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity. KRM-II-81 was active against electroshock-induced convulsions in mice, pentylenetetrazole (PTZ)-induced convulsions in rats, elevations in PTZ-seizure thresholds, and amygdala-kindled seizures in rats with efficacies greater than that of diazepam. KRM-II-81 was also active in the 6 Hz seizure model in mice. Structural analogs of KRM-II-81 but not the ester, HZ-166, were active in all models in which they were evaluated. We further evaluated KRM-II-81 in human cortical epileptic tissue where it was found to significantly-attenuate picrotoxin- and AP-4-induced increases in firing rate across an electrode array. These molecules generally had a wider margin of separation in potencies to produce anticonvulsant effects vs. motor impairment on an inverted screen test than did diazepam. Ester bioisosters of HZ-166 are thus presented as novel agents for the potential treatment of epilepsy acting via selective positive allosteric amplification of GABA_A signaling through α2/α3-containing GABA receptors. The in vivo data from the present study can serve as a guide to dosing parameters that predict engagement of central GABA_A receptors.

100 项与 AP-004 相关的药物交易

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