Publications by authors named "M A Motaleb"

64 Publications

Formulation of chitosan coated nanoliposomes for the oral delivery of colistin sulfate: characterization, Tc-radiolabeling and biodistribution studies.

Drug Dev Ind Pharm 2021 Apr 9:1-10. Epub 2021 Apr 9.

Labeled Compounds Department, Hot Lab Center, Egyptian Atomic Energy Authority, Cairo, Egypt.

Colistin sulfate is a very important antibiotic for the treatment of multidrug-resistant Gram-negative infections. Unfortunately, it has low oral bioavailability and several side effects following parenteral administration. The present study aims to develop chitosan-coated colistin nanoliposomes to improve the stability in the gastrointestinal tract and to enhance the oral delivery of colistin. The chitosan-coated colistin nanoliposomes were obtained via thin-film evaporation and electrostatic deposition methods using either Span 60, Tween 65 or Tween 80 as surfactants with different cholesterol: surfactant: soya lecithin ratios. The influence of systems variables was further characterized by vesicle size analysis, zeta potential (ZP), poly dispersibility index (PDI), and also their entrapment efficiency percentage (EE %) was evaluated. Various systems were formed with vesicle sizes in the nano-range, 155.64 ± 12.53 nm to 315.64 ± 15.90 nm, and EE % of 45.2 ± 2.9% to 81.8 ± 2.9%. Moreover, the ZP value of the prepared nanoliposomes switched from a negative to a positive value after chitosan coating. To track the released colistin technetium 99m (Tc) was incorporated into the optimum system (S-3) system via direct coupling with colistin. Chitosan-coated Tc-colistin nanoliposome, Tc-colistin suspension, and Tc-chitosan-coated nanoliposomes (placebo) were administered orally into bacterial infection () bearing mice. The biodistribution results showed that chitosan-coated nanoliposome significantly enhanced the bioavailability of colistin compared to colistin suspension (the commercially available). Moreover, the system effectively improved the localization of colistin at the infected muscle. In conclusion, this approach offers a promising tool for enhanced oral delivery of colistin.
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http://dx.doi.org/10.1080/03639045.2021.1908334DOI Listing
April 2021

Amelioration of Tumor Targeting and In Vivo Biodistribution of Tc-Methotrexate-Gold Nanoparticles (Tc-Mex-AuNPs).

J Pharm Sci 2021 Apr 2. Epub 2021 Apr 2.

Radioisotopes Production Facility, Second Egyptian Research Reactor Complex, Egyptian Atomic Energy Authority, Cairo 13759, Egypt; Radioactive Isotopes and Generator Department, Hot Labs Center, Egyptian Atomic Energy Authority, Cairo 13759, Egypt. Electronic address:

Gold nanoparticles (AuNPs) represent very attractive and promising drug delivery carriers due to their unique dimensions, adjustable surface functions, and controllable drug release. Therefore, AuNPs are used to overcome the limitations of conventional chemotherapy, for example methotrexate (Mex), one of the first-generation chemotherapy drugs for cancer treatment, whose usefulness has been restricted due to drug resistance and dose-dependent side effects. In the present study, the AuNPs drug delivery system was synthesized and loaded with technetium-99 m radiolabeled Methotrexate (Tc-Mex) to produce new potential nanoradiopharmaceutical for tumor targeting and further imaging. The Methotrexate loaded gold nanoparticles (Mex-AuNPs) successfully prepared in small spherical particle size (20.3 nm), polydispersity index PDI (< 0.5) and a zeta potential (-17.6 mV) with loading efficiency% (93 ± 1.2%) of methotrexate at 30 min as an optimum stirring time and showed strong absorption peak for Mex-AuNPs at λ, 525 nm. The in vitro release profile of Mex-AuNPs showed high release percent of methotrexate at pH 5; the Q5 h and Q were 21.2 ± 1.5% and 92.9 ± 3.4%, respectively. The in vitro cytotoxicity was investigated at different concentrations (0.024-50 μl/100 μl) of Mex-AuNPs (1 mg/ml) against MCF-7 (Michigan Cancer Foundation-7) breast cancer cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay technique. Mex-AuNPs showed higher anticancer activity with low inhibitory concentration (IC = 0.098 μl/100 μl) that was three times lower than the inhibitory concentration (IC) of methotrexate (IC = 0.3 μl/100 μl). Tc-Mex complex prepared by direct reduction method at maximum radiochemical yield (RCY)% ̴ 98.3 ± 1.09 % was loaded in AuNPs to form Tc-Mex-AuNPs with loading efficiency% (93 ± 1.2 %) at 30 min of stirring time. Tc-Mex-AuNPs showed convenient in vitro stability in mice serum up to 24 h with RCY% > 90 %. The preclinical biodistribution studies of Tc-Mex-AuNPs were performed in 3 experimental groups A (intravenous (I.V.) injected normal mice), B and C (I.V. and intratumor (I.T.) injected tumor bearing mice, respectively). The Tc-Mex-AuNPs achieved highest tumor uptake (93 ± 0.39 %ID/g) and highest Target/NonTarget (T/NT) ratio (58.1 ± 0.91) with high Tumor/Blood (T/B) ratio (25.8 ± 0.11) at 10 min post I.T. injection and retained high tumor uptake (79 ± 0.65 %ID/g) up to 60 min post I.T. injection before escaping into blood stream. Consequently, Tc-Mex-AuNPs can be considered as new potential nanoradiopharmaceutical in tumor diagnosis.
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http://dx.doi.org/10.1016/j.xphs.2021.03.021DOI Listing
April 2021

Miniaturized chromatographic systems for radiochemical purity evaluation of I-Ferulic acid as a new candidate in nuclear medicine applications.

Appl Radiat Isot 2021 Jan 8;167:109370. Epub 2020 Oct 8.

Labeled Compounds Department, Hot Laboratories Center, Egyptian Atomic Energy, P.O. 13759, Cairo, Egypt.

Recently, the anticancer activity of ferulic acid (FA) which is a caffeic acid derivative has been reported. Therefore, in this study FA was radiocaped with I to explore its potential as a tumor targeting agent. The radiolabeling process was carried out via electrophilic substitution reaction. The factors affecting labeling yield were optimized and the radiochemical purity (RCP) was assessed by various analytical techniques including paper chromatography (PC), thin layer chromatography (TLC), instant thin layer chromatography (ITLC), paper electrophoresis (PE) and high-performance liquid chromatography (HPLC). The RCP assay was extended to the utilization of miniaturized techniques including miniaturized PC (mini-PC), mini-TLC and mini-column chromatography (silica, sephadex-G25). Validation of mini-TLC, as one of I-FA RCP assay methods, was done according to ICH guidelines. Biodistribution studies of I-FA were performed on Ehrlich solid tumor bearing mice at various time points (5, 30, 60, 120 and 240 min), post injection. The radiolabeling yield of I-FA was 96.23 ± 0.45% and the miniaturized chromatographic systems showed high efficacy in RCP evaluation comparable to the conventional ones. Mini-TLC was proved to be specific, accurate, precise and linear. The tumor uptake of I-FA in solid tumor bearing mice was 4.35 ± 0.41 ID/g at 60 min with 2.79 as a tumor/muscle ratio. Consequently, I-FA could be used as a tumor targeting agent for nuclear medicine applications and the fast reaction monitoring could be achieved using miniaturized chromatographic techniques.
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http://dx.doi.org/10.1016/j.apradiso.2020.109370DOI Listing
January 2021

Molecular mechanism for rotational switching of the bacterial flagellar motor.

Nat Struct Mol Biol 2020 11 7;27(11):1041-1047. Epub 2020 Sep 7.

Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.

The bacterial flagellar motor can rotate in counterclockwise (CCW) or clockwise (CW) senses, and transitions are controlled by the phosphorylated form of the response regulator CheY (CheY-P). To dissect the mechanism underlying flagellar rotational switching, we use Borrelia burgdorferi as a model system to determine high-resolution in situ motor structures in cheX and cheY3 mutants, in which motors are locked in either CCW or CW rotation. The structures showed that CheY3-P interacts directly with a switch protein, FliM, inducing a major remodeling of another switch protein, FliG2, and altering its interaction with the torque generator. Our findings lead to a model in which the torque generator rotates in response to an inward flow of H driven by the proton motive force, and conformational changes in FliG2 driven by CheY3-P allow the switch complex to interact with opposite sides of the rotating torque generator, facilitating rotational switching.
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http://dx.doi.org/10.1038/s41594-020-0497-2DOI Listing
November 2020

Creating a Library of Random Transposon Mutants in Leptospira.

Methods Mol Biol 2020 ;2134:77-96

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.

Generation of a random transposon mutant library is advantageous in Leptospira as site-directed mutagenesis remains a challenge, especially in pathogenic species. This procedure is typically completed by transformation of Leptospira with a Himar1 containing plasmid via conjugation with Escherichia coli as a donor cell. Here we describe the methodology to generate random transposon mutants in the saprophyte Leptospira biflexa via conjugation of plasmid pSW29T-TKS2 harbored in E. coli β2163. Determination of transposon insertion site by semi-random nested PCR will also be described. A similar methodology may be employed to generate Tn mutants of pathogenic Leptospira species.
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http://dx.doi.org/10.1007/978-1-0716-0459-5_8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473121PMC
March 2021