Publications by authors named "Mohamed H Aboumanei"

6 Publications

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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

Radioiodination and in vivo assessment of the potential of newly synthesized pyrrolizine-5-carboxamides derivative in tumor model.

Appl Radiat Isot 2020 Dec 8;166:109369. Epub 2020 Aug 8.

Labeled Compounds Dept. Hot Labs Center, Atomic Energy Authority, Cairo, Egypt; Faculty of Pharmacy, Albayan University, Baghdad, Iraq.

Recently, pyrrolizine derivatives have been reported to possess numerous anticancer activities. In a previous study, (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine carboxamide (EZPCA) compound was synthesized and the cytotoxic activity of EZPCA toward COX-2 enzyme (overexpressed in cancer cells) was reported. In order to assess the suitability of this compound as a promising pilot structure for in vivo applications, EZPCA was radiolabeled with radioiodine-131 (I) and various factors affecting radiolabeling process were studied. Quality control studies of [I]iodo-EZPCA were performed using paper chromatography and HPLC was used as a co-chromatographic technique for confirming the radiochemical yield. Biodistribution studies of [I]iodo-EZPCA were undertaken in normal and tumor bearing mice. The radiochemical yield percentage of [I]iodo-EZPCA was 94.20 ± 0.12%. The biodistribution results showed evident tumor uptake of [I]iodo-EZPCA with promising target/non-target (T/NT) ratios. As a conclusion, these data suggest that [I]iodo-EZPCA had high binding efficiency, high tumor uptake and sufficient stability to be used be used in diagnostic studies.
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http://dx.doi.org/10.1016/j.apradiso.2020.109369DOI Listing
December 2020

Improved Targeting and Tumor Retention of a Newly Synthesized Antineoplaston A10 Derivative by Intratumoral Administration: Molecular Docking, Technetium 99m Radiolabeling, and In Vivo Biodistribution Studies.

Cancer Biother Radiopharm 2018 Aug 12;33(6):221-232. Epub 2018 Jun 12.

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

Background: Recently, the direct intratumoral (i.t.) injection of anticancer agents has been investigated. A newly synthesized Antineoplaston A10 analog 3-(4-methoxybenzoylamino)-2,6-piperidinedione (MPD) showed an antitumor activity in human breast cancer cell line. Unfortunately, MPD suffered from poor water solubility.

Materials And Methods: Pseudoternary phase diagram of oil (isopropyl myristate), surfactant (Tween 80), cosurfactant (ethanol), and water was plotted. MPD microemulsion (MPDME) was developed and characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and morphology (transmission electron microscopy). MPDME and MPD solution (MPDS) were radiolabeled with technetium 99m (Tc) using stannous chloride dihydrate (SnCl.2HO). Molecular docking of MPD and Tc-MPD was performed to study the interaction with DNA.

Results: The impacts of intravenous (i.v.) and i.t. injections of Tc-MPDME and Tc-MPDS on biodistribution were studied. The developed MPDME showed spherical droplets with mean PS (74.00 ± 5.69 nm), PDI (0.25 ± 0.03), and ZP (33.90 ± 0.90 mV). Labeling yield of Tc-MPDME and Tc-MPDS was 97.00% ± 0.60% and 92.02% ± 0.45%, respectively. MPD and Tc-MPD showed almost same binding affinity with DNA binding site. Biodistribution results showed that i.t. injection of Tc-MPDME significantly enhanced tumor retention compared to i.v. route.

Conclusions: Herein, the authors concluded that microemulsion could be used as i.t. injectable delivery vehicle to improve targeting and tumor retention of MPD.
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http://dx.doi.org/10.1089/cbr.2017.2431DOI Listing
August 2018

Design and development of microemulsion systems of a new antineoplaston A10 analog for enhanced intravenous antitumor activity: In vitro characterization, molecular docking, I-radiolabeling and in vivo biodistribution studies.

Int J Pharm 2018 Jul 4;545(1-2):240-253. Epub 2018 May 4.

Labeled Compounds Department, Hot Lab Center, Egyptian Atomic Energy Authority, Cairo 11371, Egypt.

A10, (3-phenylacetylamino-2,6-piperidinedione), is a natural peptide with broad antineoplastic activity. Recently, in vitro antitumor effect of a new A10 analog [3-(4-methoxybenzoylamino)-2,6-piperidinedione] (MPD) has been verified. However, poor aqueous solubility represents an obstacle towards intravenous formulation of MPD and impedes successful in vivo antitumor activity. To surmount such limitation, MPD microemulsion (MPDME) was developed. A 32 full factorial design using Design-Expert® software was adopted to study the influence of different parameters and select the optimum formulation (MPDME1). Transmission electron microscopy (TEM) displayed spherical droplets of MPDME1. The cytotoxicity of MPDME1 in Michigan Cancer Foundation 7 (MCF-7) breast cancer cell line exceeded that of MPD solution (MPDS) and tamoxifen. Compatibility with injectable diluents, in vitro hemolytic studies and in vivo histopathological examination confirmed the safety of parenteral application of MPDME1. Molecular docking results showed almost same binding affinity of A10, MPD and I-MPD with histone deacetylase 8 (HDAC8) receptor. Accordingly, radioiodination of MPDME1 and MPDS was done via direct electrophilic substitution reaction. Biodistribution of I-MPDME1 and I-MPDS in normal and tumor (ascites and solid) bearing mice showed high accumulation of I-MPDME1 in tumor tissues. Overall, the results proved that MPDME represents promising parenteral delivery system capable of improving antineoplastic activity of MPD.
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http://dx.doi.org/10.1016/j.ijpharm.2018.05.010DOI Listing
July 2018

Molecular Docking, Pharmacophore, and 3D-QSAR Approach: Can Adenine Derivatives Exhibit Significant Inhibitor Towards Ebola Virus?

Open Med Chem J 2017 30;11:127-137. Epub 2017 Nov 30.

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India.

Introduction: Ebola Virus Disease (EVD) is caused by Ebola virus, which is often accompanied by fatal hemorrhagic fever upon infection in humans. This virus has caused the majority of deaths in human. There are no proper vaccinations and medications available for EVD. It is pivoting the attraction of scientist to develop the potent vaccination or novel lead to inhibit Ebola virus.

Methods & Materials: In the present study, we developed 3D-QSAR and the pharmacophoric model from the previous reported potent compounds for the Ebola virus.

Results & Discussion: Results & Discussion: The pharmacophoric model AAAP.116 was generated with better survival value and selectivity. Moreover, the 3D-QSAR model also showed the best r2 value 0.99 using PLS factor. Thereby, we found the higher F value, which demonstrated the statistical significance of both the models. Furthermore, homological modeling and molecular docking study were performed to analyze the affinity of the potent lead. This showed the best binding energy and bond formation with targeted protein.

Conclusion: Finally, all the results of this study concluded that 3D-QSAR and Pharmacophore models may be helpful to search potent lead for EVD treatment in future.
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http://dx.doi.org/10.2174/1874104501711010127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748831PMC
November 2017

Pharmacophore, 3D-QSAR Models and Dynamic Simulation of 1,4-Benzothiazines for Colorectal Cancer Treatment.

Comb Chem High Throughput Screen 2017 ;20(8):658-674

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Rae Bareli Road, Lucknow 226025, India.

Aim And Objective: Interleukin-6 has become an attractive protein target. This is found in the progression of colon cancer. It performs various functions in the colon cancer cells such as inflammation, activates various cell types signaling and also promotes proliferation in colon cancer cells. It is a valid target to develop anticolon cancer drug. The purpose of our study is to develop the Three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models, pharmacophore modeling and docking study as well as MD simulation to find out the novel potent inhibitors that bind with Interleukin-6 in colon cancer treatment.

Material And Methods: In this study, common pharmacophore models and atom-based 3D-QSAR studies were carried out by using 1,4-benzothiazine derivatives with their experiential GI50values towards HT-29 human colon cancer cell line.

Results: The common pharmacophore model (ADHR26) was developed and the survival score was found to be 3.828. The generated pharmacophore-based alignment was used to develop a predictive atom-based 3D-QSAR model by using Partial Least Square (PLS) method. Phase predictable activity and LogGI50 also exhibited the most significant atomic position in the backbone structure of ligands for anticolon cancer activity. Molecular dynamic and docking studies for the IL-6 target provide key framework of ligand for the anticolon cancer activity.

Conclusion: Finally, results generated from the work data, that exhibited the pharmacophore models and 3D-QSAR hypothesis might be a path of milestone in the area of medicinal chemistry to researchers for further design of new and potent IL-6 inhibitors.
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http://dx.doi.org/10.2174/1386207320666170509153137DOI Listing
December 2018