Publications by authors named "Ahmed M El-Sayed"

17 Publications

  • Page 1 of 1

Severe cutaneous adverse drug reactions: Incidence, clinical patterns, causative drugs and modalities of treatment in Assiut University Hospital, Upper Egypt.

Dermatol Ther 2020 11 7;33(6):e14176. Epub 2020 Sep 7.

Faculty of Pharmacy, Department of Clinical Pharmacy, Assiut University, Assiut, Egypt.

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and overlap SJS/TEN are life-threatening diseases that are most frequently caused by drugs. Much debate remains about the role of systemic corticosteroids (SCs) in their treatment. Our aim to determine the incidence, causative drugs, the role and side effects of SCs in severe cutaneous adverse reactions (SCARs), in Assiut University Hospital (AUH). Patients This study was conducted in Department of Dermatology at AUH, from 2012 to 2017. All patients with SJS, overlap SJS/TEN and TEN admitted during this period were included in the study. Eighty-three patients with SCARs were included in this study. The most common type was SJS (67.5%). The incidence ranged from 1.7% in 2012 to 7.7% in 2017. Carbamazepine, valproic acid, lamotrigine, diclofenac sodium, and flucloxacillin-amoxicillin were the most common causative drugs. The most common side effects of SCs were peptic ulcer (55.5%) and hypertension (51.8%). The mortality rate in patients treated with SCs was 100% in TEN, 33.3% in overlap SJS/TEN and 16.3% in SJS. The patients of SCARs must be aware of the causative drugs and must never be re-administered. SCs in treatment of SCARs may increase the complications and the mortality rate.
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http://dx.doi.org/10.1111/dth.14176DOI Listing
November 2020

Stability Study and Clinical Evaluation of Lipid Injectable Emulsion in Parenteral Nutrition Admixtures Used for Preterm Neonates.

Nutr Clin Pract 2020 Jul 16. Epub 2020 Jul 16.

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt.

Background: Intravenous administration of parenteral nutrition (PN) admixtures containing 4-oil lipid injectable emulsion (ILE) in preterm neonates is usually prohibited because of limited clinical data. The authors evaluated the stability, safety, and efficacy of PN admixtures containing 4-oil ILE, for the first time, in preterm neonates.

Methods: A series of PN admixtures were prepared for consecutive administration in preterm neonates over a period of 15 days. Admixture stability was assessed after 24 hours of storage at 25 and 37 °C via visual inspection and measurement of mean droplet size (MDS). Safety and efficacy of the admixtures in preterm neonates were assessed via serum triglyceride levels and body weight increase measurements, respectively.

Results: PN admixtures were stable at 25 °C and had MDS ˂500 nm. After 15 days, there was a significant increase in body weight (P ≤ .0001) and level of serum triglycerides (P ≤ .0001), compared with the level before PN administration.

Conclusions: PN admixtures containing 4-oil ILE were stable at 25 °C and showed instability at 37 °C. Therefore, it is recommended to keep the temperature during administration of PN admixtures at 25 °C. PN admixtures were well tolerated and safe over a period of 8 days while providing a balanced fatty acid supply. Tight monitoring of serum triglyceride level is essential, particularly in neonates of low birth weight and/or young gestational age, to avoid hypertriglyceridemia. Hence, the use of these PN admixtures is expected to be beneficial in terms of being cost-effective and reducing the contamination risks.
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http://dx.doi.org/10.1002/ncp.10556DOI Listing
July 2020

Colon-targeting of progesterone using hybrid polymeric microspheres improves its bioavailability and in vivo biological efficacy.

Int J Pharm 2020 Mar 23;577:119070. Epub 2020 Jan 23.

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. Electronic address:

This study aims to enhance progesterone (PG) oral bioavailability via its incorporation into hybrid colon-targeted pectin/NaCMC microspheres (MS) cross-linked with Zn and Al. The MS were characterized for particle morphology, encapsulation efficiency, swelling behavior, drug release, mucoadhesivity and colon-specific degradability. Response-surface methodology was adopted to optimize the fabrication conditions. Enhancement of in vivo drug performance was evaluated through pharmacokinetic and pharmacodynamic studies. The optimized formulation was typically spherical with a mean diameter of 1031 µm and drug entrapment efficiency of 88.8%. This formulation exhibited pH-dependent swelling, negligible drug release in simulated gastric fluid and sustained-release pattern in simulated small intestinal fluid with a mean t of 26.5 h. It also showed prolonged and preferential adhesion to rat colonic mucosa, as well as expedited degradation in presence of rat caecal contents. The MS significantly increased the area under the curve and mean residence time by 1.8 and 2.3-fold, respectively compared to the free drug. Orally administered MS showed ~10 times increase in myometrial thickness compared with the drug suspension and elicited uterine responses very similar to that obtained parenterally. These results confirm the ability of this new carrier system to improve the oral bioavailability of PG and attain adequate clinical efficacy.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119070DOI Listing
March 2020

A Self-Nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and In Vivo Evaluation.

J Pharm Sci 2019 11 23;108(11):3599-3608. Epub 2019 Jul 23.

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

The drug delivery of candesartan cilexetil encounters an obstacle of low absolute oral bioavailability which is attributed mainly to its low aqueous solubility and efflux by intestinal P-glycoprotein (P-gp) transporters. However, the extent of P-gp contribution in the reduced oral bioavailability of candesartan cilexetil is not clear. In this study, a previously developed candesartan cilexetil-loaded self-nanoemulsifying drug delivery system (SNEDDS) was evaluated for its ability to increase the drug oral bioavailability via the inhibition of intestinal P-gp transporters. Despite the developed SNEDDS showing P-gp inhibition activity, P-gp-mediated efflux was found to have a minor role in the reduced oral bioavailability of candesartan cilexetil. On the other hand, the high surfactant concentration used in SNEDDS formulation represents a major challenge toward their widespread application especially for chronically administered drugs. The designed acute and subacute toxicity studies revealed that the degree of intestinal mucosal damage decreases as the treatment period increases. The latter observation was attributed to the reversibility of surfactant-induced mucosal damage. Thus, the developed SNEDDS could be considered as a promising delivery system for enhancing the oral bioavailability of chronically administered drugs.
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http://dx.doi.org/10.1016/j.xphs.2019.07.004DOI Listing
November 2019

Survey on Implementation of One Health Approach for MERS-CoV Preparedness and Control in Gulf Cooperation Council and Middle East Countries.

Emerg Infect Dis 2019 03;25(3)

In 2015, a One Health Working Group was established in Qatar to conduct a survey in the Gulf Cooperation Council countries, Egypt, and Jordan to monitor preparedness of public health and veterinary health authorities in response to the Middle East respiratory syndrome coronavirus epidemic. All but 1 country indicated they established joint One Health policy teams for investigation and response. However, the response to the questionnaires was largely limited to veterinary authorities. Critical barriers and limitations were identified. National and regional leaders, policy makers, and stakeholders should be prompted to advocate and enhance adoption of the One Health framework to mitigate the risk for Middle East respiratory syndrome and other emerging zoonotic diseases.
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http://dx.doi.org/10.3201/eid2503.171702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390738PMC
March 2019

Self-emulsifying drug-delivery systems modulate P-glycoprotein activity: role of excipients and formulation aspects.

Nanomedicine (Lond) 2018 Jul 3;13(14):1813-1834. Epub 2018 Aug 3.

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

Self-emulsifying drug-delivery systems (SEDDS) have been widely employed to ameliorate the oral bioavailability of P-glycoprotein (P-gp) substrate drugs and to overcome multidrug resistance in cancer cells. However, the role of formulation aspects in the reduced P-gp activity is not fully understood. In this review, we first explore the role of various SEDDS excipients in the reduced P-gp activity with the main emphasis on the effective excipient concentration range for excipient-mediated modulation of P-gp activity and then we discuss the synergistic effect of various formulation aspects on the excipient-mediated modulation of P-gp activity. This review provides an approach to develop a rationally designed SEDDS to overcome P-gp-mediated drug efflux.
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http://dx.doi.org/10.2217/nnm-2017-0354DOI Listing
July 2018

Role of self-emulsifying drug delivery systems in optimizing the oral delivery of hydrophilic macromolecules and reducing interindividual variability.

Colloids Surf B Biointerfaces 2018 Jul 26;167:82-92. Epub 2018 Mar 26.

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt. Electronic address:

Self-emulsifying drug delivery systems (SEDDS) have been widely employed to improve the oral bioavailability of poorly soluble drugs. In the past few years, SEDDS were extensively investigated to overcome various barriers encountered in the oral delivery of hydrophilic macromolecules (e.g., protein/peptide therapeutics and plasmid DNA (pDNA)), as well as in lowering the effect of food on drugs' bioavailability. However, the main mechanism(s) by which SEDDS could achieve such promising effects remains not fully understood. This review summarizes the recent progress in the use of SEDDS for protecting protein therapeutics and/or pDNA against enzymatic degradation and increasing the oral bioavailability of various drug substances regardless of the dietary condition. Understanding the underlying mechanism(s) of such promising applications will aid in the future development of rationally designed SEDDS. Entrapment of hydrophilic macromolecules in the oil phase of the formed emulsion is critical for protection of the loaded cargoes against enzymatic degradation and the enhancement of oral bioavailability. On the other hand, drug administration as a preconcentrated solution in the SEDDS preconcentrate allows the process of drug absorption to occur independently of the dietary condition, and thus reducing interindividual variability that results from concomitant food intake.
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http://dx.doi.org/10.1016/j.colsurfb.2018.03.034DOI Listing
July 2018

Development and in vitro/in vivo performance of self-nanoemulsifying drug delivery systems loaded with candesartan cilexetil.

Eur J Pharm Sci 2017 Nov 6;109:503-513. Epub 2017 Sep 6.

Department of pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. Electronic address:

Candesartan cilexetil is widely used in the management of hypertension and heart failure. The drug delivery encounters obstacles of poor aqueous solubility, efflux by intestinal P-glycoprotein and vulnerability to enzymatic degradation in small intestine. Self-nanoemulsifying drug delivery systems (SNEDDS) loaded with candesartan cilexetil were successfully developed to overcome such obstacles. Preliminary screening was carried out to select proper surfactant, co-surfactant and oil combination for successful SNEDDS formulation. All screened excipients were reported for their P-glycoprotein and cytochrome P450 3A4 (CYP3A4) modulation activity. Ternary and pseudo ternary diagrams were constructed to optimize the system. Peppermint oil and clove oil showed a high emulsification ability. The nature of obtained dispersions was identified to be nanoemulsions. Twenty-four formulations were evaluated for stability, robustness to dilution and self-emulsification efficiency. All formulations showed a very short emulsification time of <2min. The emulsification efficiency was significantly superior at pH6.8, at which the largest self-emulsifying region was also observed. Eight formulations were selected for further characterization according to cloud point measurement; mean droplet size, poly dispersity index (PDI) and zeta potential determination in addition to in vitro drug release study. All selected formulations showed very high cloud points (70-90°C), ultrafine mean droplet size (12±1.4 to 24.5±2.13nm), very low PDI values (0.015-0.1305) and almost a complete drug release after 12h. Formulation F15 (Peppermint oil 55% w/w: Cremophor RH40 25% w/w: Labrasol 20% w/w) was selected for further characterization. Its droplet size showed robustness to different dilution folds with different media and its TEM photograph showed spherical particles without any apparent aggregation even after 24h. Formulation F15 successfully controlled the systolic blood pressure of hypertensive rats for 24h with the maximum effect was observed after 2h. These results indicate that, SNEDDS could be promising delivery systems with a rapid onset of action and prolonged therapeutic effect of candesartan cilexetil.
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http://dx.doi.org/10.1016/j.ejps.2017.09.001DOI Listing
November 2017

Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Infection in Camel Workers in Qatar During 2013-2014: A Case-Control Study.

J Infect Dis 2017 06;215(11):1702-1705

Department of Viroscience, Erasmus Medical Center,Rotterdam, the Netherlands.

The transmission routes and risk factors for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infections are still unknown. We used the World Health Organization questionnaire for MERS-CoV case-control studies to assess risk factors for human MERS-CoV seropositivity at a farm complex in Qatar. Nine camel workers with MERS-CoV antibodies and 43 workers without antibodies were included. Some camel-related activities may pose a higher risk of MERS-CoV infection, as may cross-border movements of camels, poor hand hygiene, and overnight hospital stays with respiratory complaints. The risk factors identified in this study can be used to develop infection prevention and control measures for human MERS-CoV infections.
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http://dx.doi.org/10.1093/infdis/jix174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107360PMC
June 2017

Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone.

Drug Deliv 2016 Sep 8;23(7):2541-2554. Epub 2015 Apr 8.

a Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut , Egypt.

The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (∼25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 µm were obtained. Drug entrapment efficiency of ∼75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ∼168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.
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http://dx.doi.org/10.3109/10717544.2015.1028602DOI Listing
September 2016

Amidated pectin/sodium carboxymethylcellulose microspheres as a new carrier for colonic drug targeting: Development and optimization by factorial design.

Carbohydr Polym 2016 Nov 6;153:526-534. Epub 2016 Aug 6.

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. Electronic address:

The colon is a promising site for drug targeting owing to its long transit time and mild proteolytic activity. The aim of this study was to prepare new low methoxy amidated pectin/NaCMC microspheres cross-linked by a mixture of Zn(2+) and Al(3+) ions and test their potential for colonic targeting of progesterone. A 2(4) factorial design was carried out to optimize the preparation conditions. High drug entrapment efficiency (82-99%) was obtained and it increased with increasing drug concentration but decreased with increasing polymer concentration. Drug release rate was directly proportional to the microsphere drug content and inversely related to Al(3+) ion concentration. Drug release was minimal during the first 3h but was significantly improved in the presence of 1% rat caecal contents, confirming the microsphere potential for colonic delivery. The microspheres achieved >2.3-fold enhancement of colonic progesterone permeability. These results confirm the viability of the produced microspheres as colon-targeted drug delivery vehicle.
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http://dx.doi.org/10.1016/j.carbpol.2016.08.018DOI Listing
November 2016

Aggressive Lymphoma "Sarcoma Mimicker" Originating in the Gluteus and Adductor Muscles: A Case Report and Literature Review.

Clin Med Insights Case Rep 2016 5;9:47-53. Epub 2016 Jul 5.

Hematology Consultant, Department of Hematology and BMT, National Center for Cancer Care and Research (NCCCR)-Hamad Medical Corporation (HMC), Doha, Qatar.

Extranodal lymphoma (ENL) occurs in approximately 30%-40% of all patients with non-Hodgkin lymphoma and has been described in almost all organs and tissues. However, diffuse large B-cell lymphoma is the most common histological subtype of non-Hodgkin lymphoma, primarily arising in the retroperitoneal region. In this article, we report a rare case of an adult male diagnosed with primary diffuse large B-cell lymphoma of the gluteal and adductor muscles with aggressive bone involvement. All appropriate radiological and histopathological studies were done for diagnosis and staging. After discussion with the lymphoma multidisciplinary team, it was agreed to start on R-CHOP protocol (rituximab, cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin®), and prednisone) as the standard of care, which was later changed to R-CODOX-M/R-IVAC protocol (rituximab, cyclophosphamide, vincristine (Oncovin®), doxorubicin, and high-dose methotrexate alternating with rituximab, ifosfamide, etoposide, and high-dose cytarabine) due to inadequate response. Due to the refractory aggressive nature of the disease, subsequent decision of the multidisciplinary team was salvage chemotherapy and autologous stem cell transplant. The aim of this case report was to describe and evaluate the clinical presentation and important radiological features of extranodal lymphoma affecting the musculoskeletal system.
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http://dx.doi.org/10.4137/CCRep.S39052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934407PMC
July 2016

Occupational Exposure to Dromedaries and Risk for MERS-CoV Infection, Qatar, 2013-2014.

Emerg Infect Dis 2015 Aug;21(8):1422-5

We determined the presence of neutralizing antibodies to Middle East respiratory syndrome coronavirus in persons in Qatar with and without dromedary contact. Antibodies were only detected in those with contact, suggesting dromedary exposure as a risk factor for infection. Findings also showed evidence for substantial underestimation of the infection in populations at risk in Qatar.
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http://dx.doi.org/10.3201/eid2108.150481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517733PMC
August 2015

High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014.

Infect Ecol Epidemiol 2015 15;5:28305. Epub 2015 Jul 15.

Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.

Two of the earliest Middle East respiratory syndrome (MERS) cases were men who had visited the Doha central animal market and adjoining slaughterhouse in Qatar. We show that a high proportion of camels presenting for slaughter in Qatar show evidence for nasal MERS-CoV shedding (62/105). Sequence analysis showed the circulation of at least five different virus strains at these premises, suggesting that this location is a driver of MERS-CoV circulation and a high-risk area for human exposure. No correlation between RNA loads and levels of neutralizing antibodies was observed, suggesting limited immune protection and potential for reinfection despite previous exposure.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505336PMC
http://dx.doi.org/10.3402/iee.v5.28305DOI Listing
July 2015

Isolation of MERS coronavirus from a dromedary camel, Qatar, 2014.

Emerg Infect Dis 2014 Aug;20(8):1339-42

We obtained the full genome of Middle East respiratory syndrome coronavirus (MERS-CoV) from a camel in Qatar. This virus is highly similar to the human England/Qatar 1 virus isolated in 2012. The MERS-CoV from the camel efficiently replicated in human cells, providing further evidence for the zoonotic potential of MERS-CoV from camels.
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http://dx.doi.org/10.3201/eid2008.140663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111206PMC
August 2014

Theory, methods, and applications of fractional calculus.

ScientificWorldJournal 2014 9;2014:249717. Epub 2014 Jun 9.

Mathematics Department, Faculty of Science, Alexandria University, Alexandria 21526, Egypt.

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http://dx.doi.org/10.1155/2014/249717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071982PMC
April 2015