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'Active targeting' refers to modifying a nanocarrier's surface with targeting ligands. This study introduced an efficient approach for immobilizing imidazole-based drugs onto the metallated-porphyrin complex within the porphysome nanocarrier. To enhance cellular and bacterial uptake, a Ni-porphyrin with a fatty acid tail was synthesized and placed in the bilayer center of DPPC, facilitating receptor-mediated endocytosis. The Ni-porphyrin in the head group of the Ni-porphyrin-tail was placed superficially in the polar region of the membrane. Spherical unilamellar vesicle formation (DPPC: Ni-porphyrin-tail 4:1 mole ratio), as metallo-porphysome, was achieved through supramolecular self-assembly in an aqueous buffer. These vesicles exhibited a diameter of 279 ± 7 nm and a zeta potential of −15.3 ± 2.5 mV, showcasing their unique cytocompatibility. Nitroimidazole was decorated on the surface of metallo-porphysomes and pistachio green hull extract (PGHE) was loaded into the carrier for synergistic activity against (E. coli) and (S. aureus) bacteria strains. The physicochemical properties of Nitroimidazole-porphysome-PGHE, including size, zeta potential, morphology, loading efficiency, and release profile under various pH and temperature conditions in simulated gastrointestinal fluids were characterized. This combination therapy prevented bacterial cell attachment and biofilm formation in Caco-2 cells, as colon epithelial cells. The remarkable benefit of this system is that it does not affect cell viability even at 0.5 mg/ml. This study demonstrates the potential of a new co-delivery system using biocompatible metallo-porphysomes to decrease bacterial infections. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is the most common pathogen that causes chronic lung infections and recurrence of the disease in cystic fibrosis patients by hiding inside cells and biofilm matrix. Herein, we developed gentamicin and curcumin-loaded lipid-polymer hybrid nanoparticle- (termed CG-HNPs) to evaluate in vitro activities against biofilm-embedded P. aeruginosa and compared with lipid nanoparticles containing the same drugs (CG-Lip). The nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy, which demonstrated that HNPs with a diameter of approximately 340 nm were uniform. The optimal CG-HNPs formulation illustrated high encapsulation (∼70%) and controlled release characteristics (gradually released in 72 h). The antibacterial activities of generated nanoparticles are maintained against planktonic and biofilm bacteria and it is effective in damage established biofilms. Besides, HNPs were biocompatible and nontoxic to J774 and HFF cell lines and uptake by the macrophages (J774), which facilitated the killing of intracellular bacteria in macrophages. These results introduced CG-HNPs as a promising antibacterial agent for the treatment of chronic infections and intracellular bacteria due to excellent antibacterial activity. [ABSTRACT FROM AUTHOR]

Imidazolium-based ionic liquid functionalized PEGylated mesoporous silica nanoparticles MCM-41 (denoted as [ImIL-PEGylated@MCM-41] NPs) is synthesized and evaluated as an efficient and reliable pH-sensitive nano-carrier for controlled release of cationic Lapatinib (Lap) drug. This nano-DDS was fully characterized by dynamic light scattering, scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, N2 adsorption–desorption measurement, and differential scanning calorimeter. Furthermore, the drug loading content and in-vitro drug release profile were studied. The entrapment and loading efficiency of the optimized formulation for Lap were 91 ± 2.0% and 32.21 ± 2.70%, respectively. The results of cytotoxicity assay demonstrated that ImIL-PEG@MCM-41 has no significant toxicity on both cancerous and normal cell lines and the anticancer activity of Lap@ImIL-PEG@MCM-41 was comparable to free drug in case of human breast cells (SKBR3) and human embryonic kidney 293 cells (HEK-293). Meanwhile, three-dimensional (3D) cell culture was performed by multicellular tumor spheroids for understanding of cell response to drugs in physiologically 3D microenvironments. The results of Lap@ImIL-PEG@MCM-41 uptake during 48 hours showed a gradual release of the Lap through the multicellular tumor spheroids. This showed that the pH-responsive controlled release of Lapatinib leads to the satisfactory results in the in vitro breast cancer therapy. [ABSTRACT FROM AUTHOR]

Poly-L-lysine-coated superparamagnetic iron oxide nanoparticles (SPIONs-PLL) were prepared and used as a novel-carrier for the transfer of brain-derived neurotrophic factor (BDNF) into neural stem cells (NSCs) under the beneficial influence of an external magnetic field. Pro-BDNF, a gene from human brain cDNA libraries, was obtained by polymerase chain reaction and constructed in a mammalian expression vector (PSecTag2/HygroB). The nanoparticles (NPs) were examined using Fourier transform infrared spectroscopy, zeta potential, and Transmission electron microscopy. From the results, the levels of BDNF among the transfected and untransfected cells were 30.326 ± 5.9 and 5.85 ± 3.11 pg/mL, respectively, as detected by an ELISA method. Moreover, the enhanced green fluorescent protein vector was used to evaluate the gene expression efficiency for SPIONs-PLL as a non-viral carrier in NSCs. This was performed under the influence of a magnetic field and the transfection reagents (such as Lipofectamine 2000), which served as a positive control. The histological analysis revealed that the concentration of intracellular NPs was significantly higher than intercellular NPs. These results suggest that SPIONs-PLL can serve as a novel alternative for the transfection of BDNF-NSCs and could be used in gene therapy. [ABSTRACT FROM AUTHOR]

Two novel structurally related phosphoramidate compounds, 1 and 2, with likely β-diketone system were synthesized and characterized by 1H, 13C, 31P NMR, IR spectroscopy and elemental analysis. Compound 2 exhibited a 31P NMR signal which was significantly shielded (8 ppm) relative to compound 1. Determination of human erythrocyte acetylcholinesterase (hAChE) inhibitory activity was carried out according to Ellman's modified kinetic method and the IC50 values of compounds 1 and 2 were 1.567 and 2.986 mM, respectively. The ki values of 1 and 2 were 1.39 to 2.65 min- 1 respectively. A comparison of the bimolecular rate constant (ki) and IC50 values for the irreversible inhibitors 1 and 2 revealed that the oxono analogue has greater affinity for hAChE than the thiono compound. Furthermore effects of two conventional oximes paralidoxime (A) and obidoxime (B) on reactivation of the inhibited hAChE were studied but low reactivity was shown by both the oximes. [ABSTRACT FROM AUTHOR]

Carbacylamidophosphates with the general formula RC(O)NHP(O)R1R2 constitute organophosphorus compounds that are used as insecticides, pesticides and ureas inhibitors. In this work, we studied the inhibition potency of CCl3 C(O)NHP(O)Cl21, CHCl2C(O)NHP(O)Cl22, CH2ClC(O)NHP(O)Cl23 and CF3C(O)NHP(O)Cl24, which are the major intermediates for carbacylamidophosphates synthesis towards human erythrocyte acetylcholinesterase (hAChe) activity using Ellman's modified kinetic method. Unexpectedly, it was observed that they were not only hydrolytically unstable but also inhibited hAChE in a similar manner to that produced by organophosphorus insecticides. Enzymatic data, bimolecular inhibition rate constants (ki) and IC50 values for inhibition of hAChE demonstrated that they are irreversible inhibitors and the inhibition potency of compound 2 (IC50 = 88 µM) was the greatest in comparison with compounds 1, 3 and 4. Also the electropositivity of the phosphorus atom and the hydrophobicity of the compounds demonstrated that these two factors play an additional effect and different role in the inhibitory activity of these compounds. Hydrolytic stability of the compounds was determined by Zip NMR monitoring of the loss of the parent molecules with D20 as a function of time. This study considers antiacetylcholinesterase activity according to the structural and the electronic aspects of compounds 1 4, according to IR, ¹H, 13C and 31P NMR spectral data. [ABSTRACT FROM AUTHOR]

Cholinesterases are targets for organophosphorus compounds which are used as pesticides, insecticides, chemical warfare agents and drugs for the treatment of disease such as glaucoma or parasitic infections. Most organophosphorus compounds impart their toxic action via inhibition of cholinesterases by reacting at an essential serine hydroxyl group. The inhibition process depends on the leaving group, stereochemistry and reactivity of the organophosphorus compound. In this study, the inhibitory potency of two isoelectronic and isostructural diaza- and dioxophospholes A (CH 3 C 6 H 3 O 2 P(O)Cl) and B (CH 3 C 6 H 3 (NH) 2 P(O)Cl) against human acetylcholinesterase (hAChE) was examined by spectrophotometric measurements based on Ellman's method. Results indicated that compounds A and B were irreversible inhibitors with IC 50 values of 0.48 and 1.54 mM, respectively and inactivation constants (k i ) of 0.0363 and 0.0207 min -1 , respectively. The differences in the inhibitory potency of two phosphole compounds is discussed with respect to their structures. In addition, the synthesis and characterization of compound A is discussed. [ABSTRACT FROM AUTHOR]