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Mohamed A. Alfaleh
Faculty of Pharmacy, King Abdulaziz University, Jeddah 21859, Saudi Arabia

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Journal article
Published: 04 August 2021 in Vaccines
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The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

ACS Style

Khalid Alluhaybi; Rahaf Alharbi; Rowa Alhabbab; Najwa Aljehani; Sawsan Alamri; Mohammad Basabrain; Rehaf Alharbi; Wesam Abdulaal; Mohamed Alfaleh; Levi Tamming; Wanyue Zhang; Mazen Hassanain; Abdullah Algaissi; Adel Abuzenadah; Xuguang Li; Anwar Hashem. Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1. Vaccines 2021, 9, 852 .

AMA Style

Khalid Alluhaybi, Rahaf Alharbi, Rowa Alhabbab, Najwa Aljehani, Sawsan Alamri, Mohammad Basabrain, Rehaf Alharbi, Wesam Abdulaal, Mohamed Alfaleh, Levi Tamming, Wanyue Zhang, Mazen Hassanain, Abdullah Algaissi, Adel Abuzenadah, Xuguang Li, Anwar Hashem. Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1. Vaccines. 2021; 9 (8):852.

Chicago/Turabian Style

Khalid Alluhaybi; Rahaf Alharbi; Rowa Alhabbab; Najwa Aljehani; Sawsan Alamri; Mohammad Basabrain; Rehaf Alharbi; Wesam Abdulaal; Mohamed Alfaleh; Levi Tamming; Wanyue Zhang; Mazen Hassanain; Abdullah Algaissi; Adel Abuzenadah; Xuguang Li; Anwar Hashem. 2021. "Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1." Vaccines 9, no. 8: 852.

Journal article
Published: 20 July 2021 in Viruses
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Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection compared to the general population. Here, we aimed to evaluate and characterize the SARS-CoV-2 seropositivity rate in randomly collected samples among HCWs from the largest referral hospitals and quarantine sites during the peak of the COVID-19 epidemic in the city of Jeddah, the second largest city in Saudi Arabia, using a cross-sectional analytic study design. Out of 693 participants recruited from 29 June to 10 August 2020, 223 (32.2%, 95% CI: 28.8–35.8) were found to be confirmed seropositive for SARS-CoV-2 antibodies, and among those 197 (88.3%) had never been diagnosed with COVID-19. Seropositivity was not significantly associated with participants reporting COVID-19 compatible symptoms as most seropositive HCW participants 140 (62.8%) were asymptomatic. The large proportion of asymptomatic SARS-CoV-2 cases detected in our study demands periodic testing as a general hospital policy.

ACS Style

Rowa Alhabbab; Ahdab Alsaieedi; Abdullah Algaissi; Sara Almahboub; Rajaa Al-Raddadi; Omaima Shabouni; Rahaf Alhabbab; Abdulelah Alfaraj; Sawsan Alamri; Najwa Aljehani; Rwaa Abdulal; Mohamed Alfaleh; Turki Abujamel; Almohanad Alkayyal; Ahmad Mahmoud; Adel Abuzenadah; Anwar Hashem. Seroprevalence of SARS-CoV-2 Binding and Neutralizing Antibodies in Healthcare Workers during the Epidemic Peak in Referral Hospitals and Quarantine Sites: Saudi Arabia. Viruses 2021, 13, 1413 .

AMA Style

Rowa Alhabbab, Ahdab Alsaieedi, Abdullah Algaissi, Sara Almahboub, Rajaa Al-Raddadi, Omaima Shabouni, Rahaf Alhabbab, Abdulelah Alfaraj, Sawsan Alamri, Najwa Aljehani, Rwaa Abdulal, Mohamed Alfaleh, Turki Abujamel, Almohanad Alkayyal, Ahmad Mahmoud, Adel Abuzenadah, Anwar Hashem. Seroprevalence of SARS-CoV-2 Binding and Neutralizing Antibodies in Healthcare Workers during the Epidemic Peak in Referral Hospitals and Quarantine Sites: Saudi Arabia. Viruses. 2021; 13 (7):1413.

Chicago/Turabian Style

Rowa Alhabbab; Ahdab Alsaieedi; Abdullah Algaissi; Sara Almahboub; Rajaa Al-Raddadi; Omaima Shabouni; Rahaf Alhabbab; Abdulelah Alfaraj; Sawsan Alamri; Najwa Aljehani; Rwaa Abdulal; Mohamed Alfaleh; Turki Abujamel; Almohanad Alkayyal; Ahmad Mahmoud; Adel Abuzenadah; Anwar Hashem. 2021. "Seroprevalence of SARS-CoV-2 Binding and Neutralizing Antibodies in Healthcare Workers during the Epidemic Peak in Referral Hospitals and Quarantine Sites: Saudi Arabia." Viruses 13, no. 7: 1413.

Preprint
Published: 28 June 2021
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The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b compared to IgG1. Furthermore, we found that immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicates that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

ACS Style

Khalid A. Alluhaybi; Rahaf H. Alharbi; Rowa Y. Alhabbab; Najwa D Aljehani; Sawsan S. Alamri; Mohammad Basabrain; Rehaf Alharbi; Wesam H. Abdulaal; Mohamed A. Alfaleh; Levi Tamming; Wanyue Zhang; Mazen Hassanain; Abdullah Algaissi; Adel M. Abuzenadah; Xuguang Li; Anwar M Hashem. Cellular and humoral immunogenicity of a candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1. 2021, 1 .

AMA Style

Khalid A. Alluhaybi, Rahaf H. Alharbi, Rowa Y. Alhabbab, Najwa D Aljehani, Sawsan S. Alamri, Mohammad Basabrain, Rehaf Alharbi, Wesam H. Abdulaal, Mohamed A. Alfaleh, Levi Tamming, Wanyue Zhang, Mazen Hassanain, Abdullah Algaissi, Adel M. Abuzenadah, Xuguang Li, Anwar M Hashem. Cellular and humoral immunogenicity of a candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1. . 2021; ():1.

Chicago/Turabian Style

Khalid A. Alluhaybi; Rahaf H. Alharbi; Rowa Y. Alhabbab; Najwa D Aljehani; Sawsan S. Alamri; Mohammad Basabrain; Rehaf Alharbi; Wesam H. Abdulaal; Mohamed A. Alfaleh; Levi Tamming; Wanyue Zhang; Mazen Hassanain; Abdullah Algaissi; Adel M. Abuzenadah; Xuguang Li; Anwar M Hashem. 2021. "Cellular and humoral immunogenicity of a candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1." , no. : 1.

Journal article
Published: 14 June 2021 in International Journal of Environmental Research and Public Health
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Children spend most of their daily time indoors. Many of the items used indoors, such as furniture, electronics, textile, and children toys, are treated with chemicals to provide longevity and fulfil the safety standards. However, many chemicals added to these products are released into the environment during leaching out from the treated products. Many studies have reported brominated flame retardants (BFRs) in indoor environments; however, few have focused on environments specified for young children. In this study, paired air (PM10) and dust samples were collected from the rooms (n = 30) of Saudi children. These samples were analyzed for different congeners of polybrominated diphenyl ethers (PBDEs) and three important alternative flame retardants using gas chromatography-mass spectrometry. Decabromodiphenyl ether (BDE 209) was the most important analyzed BFR in dust and PM10 samples with a median value of 3150 ng/g of dust and 75 pg/m3. This indicates the wider application of BDE 209 has implications for its occurrence, although its use has been regulated for specified uses since 2014. Among alternative BFRs, 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), Bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), and 1,2-Bis(2,4,6-tribromophenoxy)ethane (BTBPE) were found with a median levels of 10, 15 and 8 ng/g of dust, respectively. However, alternative BFRs were present in <50% of the PM10 samples. The calculated long term and daily exposures via indoor dust and PM10 of Saudi children from their rooms were well below the respective reference dose (RfD) values. Nonetheless, the study highlights BDE 209 at higher levels than previously reported from household dust in Saudi Arabia. The study warrants further extensive research to estimate the different classes of chemical exposure to children from their rooms.

ACS Style

Douha Bannan; Nadeem Ali; Nabil Alhakamy; Mohamed Alfaleh; Waleed Alharbi; Muhammad Rashid; Nisreen Rajeh; Govindan Malarvannan. Brominated Flame Retardants in Children’s Room: Concentration, Composition, and Health Risk Assessment. International Journal of Environmental Research and Public Health 2021, 18, 6421 .

AMA Style

Douha Bannan, Nadeem Ali, Nabil Alhakamy, Mohamed Alfaleh, Waleed Alharbi, Muhammad Rashid, Nisreen Rajeh, Govindan Malarvannan. Brominated Flame Retardants in Children’s Room: Concentration, Composition, and Health Risk Assessment. International Journal of Environmental Research and Public Health. 2021; 18 (12):6421.

Chicago/Turabian Style

Douha Bannan; Nadeem Ali; Nabil Alhakamy; Mohamed Alfaleh; Waleed Alharbi; Muhammad Rashid; Nisreen Rajeh; Govindan Malarvannan. 2021. "Brominated Flame Retardants in Children’s Room: Concentration, Composition, and Health Risk Assessment." International Journal of Environmental Research and Public Health 18, no. 12: 6421.

Journal article
Published: 17 March 2021 in Polymers
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Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ± 6.0 and 79.43 ± 12.43 µg/cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.

ACS Style

Shadab; Nabil Alhakamy; Hibah Aldawsari; Mohammad Husain; Nazia Khan; Mohamed Alfaleh; Hani Asfour; Yassine Riadi; Anwar Bilgrami; Habban Akhter. Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy. Polymers 2021, 13, 923 .

AMA Style

Shadab, Nabil Alhakamy, Hibah Aldawsari, Mohammad Husain, Nazia Khan, Mohamed Alfaleh, Hani Asfour, Yassine Riadi, Anwar Bilgrami, Habban Akhter. Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy. Polymers. 2021; 13 (6):923.

Chicago/Turabian Style

Shadab; Nabil Alhakamy; Hibah Aldawsari; Mohammad Husain; Nazia Khan; Mohamed Alfaleh; Hani Asfour; Yassine Riadi; Anwar Bilgrami; Habban Akhter. 2021. "Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy." Polymers 13, no. 6: 923.

Brief report
Published: 19 December 2020 in Pathogens
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The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally. Although several rapid commercial serological assays have been developed, little is known about their performance and accuracy in detecting SARS-CoV-2-specific antibodies in COVID-19 patient samples. Here, we have evaluated the performance of seven commercially available rapid lateral flow immunoassays (LFIA) obtained from different manufacturers, and compared them to in-house developed and validated ELISA assays for the detection of SARS-CoV-2-specific IgM and IgG antibodies in RT-PCR-confirmed COVID-19 patients. While all evaluated LFIA assays showed high specificity, our data showed a significant variation in sensitivity of these assays, which ranged from 0% to 54% for samples collected early during infection (3–7 days post symptoms onset) and from 54% to 88% for samples collected at later time points during infection (8–27 days post symptoms onset). Therefore, we recommend prior evaluation and validation of these assays before being routinely used to detect IgM and IgG in COVID-19 patients. Moreover, our findings suggest the use of LFIA assays in combination with other standard methods, and not as an alternative.

ACS Style

Anwar M. Hashem; Rowa Y. Alhabbab; Abdullah Algaissi; Mohamed A. AlFaleh; Sharif Hala; Turki S. Abujamel; M-Zaki ElAssouli; Afrah A. Al-Somali; Fadwa S. Alofi; Asim A. Khogeer; Almohanad A. Alkayyal; Ahmad Bakur Mahmoud; Naif A. M. Almontashiri; Arnab Pain. Performance of Commercially Available Rapid Serological Assays for the Detection of SARS-CoV-2 Antibodies. Pathogens 2020, 9, 1067 .

AMA Style

Anwar M. Hashem, Rowa Y. Alhabbab, Abdullah Algaissi, Mohamed A. AlFaleh, Sharif Hala, Turki S. Abujamel, M-Zaki ElAssouli, Afrah A. Al-Somali, Fadwa S. Alofi, Asim A. Khogeer, Almohanad A. Alkayyal, Ahmad Bakur Mahmoud, Naif A. M. Almontashiri, Arnab Pain. Performance of Commercially Available Rapid Serological Assays for the Detection of SARS-CoV-2 Antibodies. Pathogens. 2020; 9 (12):1067.

Chicago/Turabian Style

Anwar M. Hashem; Rowa Y. Alhabbab; Abdullah Algaissi; Mohamed A. AlFaleh; Sharif Hala; Turki S. Abujamel; M-Zaki ElAssouli; Afrah A. Al-Somali; Fadwa S. Alofi; Asim A. Khogeer; Almohanad A. Alkayyal; Ahmad Bakur Mahmoud; Naif A. M. Almontashiri; Arnab Pain. 2020. "Performance of Commercially Available Rapid Serological Assays for the Detection of SARS-CoV-2 Antibodies." Pathogens 9, no. 12: 1067.

Journal article
Published: 04 December 2020 in Viruses
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The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Antigen-specific responses are of unquestionable value for clinical management of COVID-19 patients. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized COVID-19 patients with different disease presentations (i.e., mild, moderate or severe), need for intensive care units (ICU) admission or outcomes (i.e., survival vs death). We show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Interestingly, significantly higher levels of nAbs as well as anti-S1 and -N IgG and IgM antibodies were found in patients with more severe symptoms, patients requiring admission to ICU or those with fatal outcomes. More importantly, early after symptoms onset, we found that the levels of anti-N antibodies correlated strongly with disease severity. Collectively, these findings provide new insights into the kinetics of antibody responses in COVID-19 patients with different disease severity.

ACS Style

Anwar M. Hashem; Abdullah Algaissi; Sarah A. Almahboub; Mohamed A. Alfaleh; Turki S. Abujamel; Sawsan S. Alamri; Khalid A. Alluhaybi; Haya I. Hobani; Rahaf H. AlHarbi; Reem M. Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K. Alharbi; Rowa Y. Alhabbab; Ahdab A. AlSaieedi; Wesam H. Abdulaal; Abdullah Bukhari; Afrah A. Al-Somali; Fadwa S. Alofi; Asim A. Khogeer; Arnab Pain; Almohanad A. Alkayyal; Naif A. M. Almontashiri; Ahmad Bakur Mahmoud; Xuguang Li. Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients. Viruses 2020, 12, 1390 .

AMA Style

Anwar M. Hashem, Abdullah Algaissi, Sarah A. Almahboub, Mohamed A. Alfaleh, Turki S. Abujamel, Sawsan S. Alamri, Khalid A. Alluhaybi, Haya I. Hobani, Rahaf H. AlHarbi, Reem M. Alsulaiman, M-Zaki ElAssouli, Sharif Hala, Naif K. Alharbi, Rowa Y. Alhabbab, Ahdab A. AlSaieedi, Wesam H. Abdulaal, Abdullah Bukhari, Afrah A. Al-Somali, Fadwa S. Alofi, Asim A. Khogeer, Arnab Pain, Almohanad A. Alkayyal, Naif A. M. Almontashiri, Ahmad Bakur Mahmoud, Xuguang Li. Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients. Viruses. 2020; 12 (12):1390.

Chicago/Turabian Style

Anwar M. Hashem; Abdullah Algaissi; Sarah A. Almahboub; Mohamed A. Alfaleh; Turki S. Abujamel; Sawsan S. Alamri; Khalid A. Alluhaybi; Haya I. Hobani; Rahaf H. AlHarbi; Reem M. Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K. Alharbi; Rowa Y. Alhabbab; Ahdab A. AlSaieedi; Wesam H. Abdulaal; Abdullah Bukhari; Afrah A. Al-Somali; Fadwa S. Alofi; Asim A. Khogeer; Arnab Pain; Almohanad A. Alkayyal; Naif A. M. Almontashiri; Ahmad Bakur Mahmoud; Xuguang Li. 2020. "Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients." Viruses 12, no. 12: 1390.

Other
Published: 23 September 2020
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The Coronavirus Disease 2019 (COVID-19), caused by the novel SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Immunological surrogate markers, in particular antigen-specific responses, are of unquestionable value for clinical management of patients with COVID-19. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized patients with RT-PCR confirmed COVID-19 infection. Our data show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Notably, anti-S and -N IgG, peaked 20-40 day after disease onset, and were still detectable for at least up to 70 days, with nAbs observed during the same time period. Moreover, nAbs titers were strongly correlated with IgG antibodies. Significantly higher levels of nAbs as well as anti-S1 and N IgG and IgM antibodies were found in patients with more severe clinical presentations, patients requiring admission to intensive care units (ICU) or those with fatal outcomes. Interestingly, lower levels of antibodies, particularly anti-N IgG and IgM in the first 15 days after symptoms onset, were found in survivors and those with mild clinical presentations. Collectively, these findings provide new insights into the characteristics and kinetics of antibody responses in COVID-19 patients with different disease severity.

ACS Style

Anwar M Hashem; Abdullah Algaissi; Sarah A Almahboub; Mohamed A Alfaleh; Turki S Abujamel; Sawsan S Alamri; Khalid A Alluhaybi; Haya I Hobani; Rahaf H AlHarbi; Reem M Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K Alharbi; Rowa Y Alhabbab; Ahdab A AlSaieedi; Wesam H Abdulaal; Abdullah Bukhari; Afrah A Al-Somali; Fadwa S Alofi; Asim A Khogeer; Arnab Pain; Almohanad A Alkayyal; Naif Am Almontashiri; Ahmad Bakur Mahmoud; Xuguang Li. Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients. 2020, 1 .

AMA Style

Anwar M Hashem, Abdullah Algaissi, Sarah A Almahboub, Mohamed A Alfaleh, Turki S Abujamel, Sawsan S Alamri, Khalid A Alluhaybi, Haya I Hobani, Rahaf H AlHarbi, Reem M Alsulaiman, M-Zaki ElAssouli, Sharif Hala, Naif K Alharbi, Rowa Y Alhabbab, Ahdab A AlSaieedi, Wesam H Abdulaal, Abdullah Bukhari, Afrah A Al-Somali, Fadwa S Alofi, Asim A Khogeer, Arnab Pain, Almohanad A Alkayyal, Naif Am Almontashiri, Ahmad Bakur Mahmoud, Xuguang Li. Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients. . 2020; ():1.

Chicago/Turabian Style

Anwar M Hashem; Abdullah Algaissi; Sarah A Almahboub; Mohamed A Alfaleh; Turki S Abujamel; Sawsan S Alamri; Khalid A Alluhaybi; Haya I Hobani; Rahaf H AlHarbi; Reem M Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K Alharbi; Rowa Y Alhabbab; Ahdab A AlSaieedi; Wesam H Abdulaal; Abdullah Bukhari; Afrah A Al-Somali; Fadwa S Alofi; Asim A Khogeer; Arnab Pain; Almohanad A Alkayyal; Naif Am Almontashiri; Ahmad Bakur Mahmoud; Xuguang Li. 2020. "Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients." , no. : 1.

Journal article
Published: 12 August 2020 in Pharmaceutics
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Thymoquinone (TQ), a natural polyphenol, has been associated with various pharmacological responses; however, low bioavailability of TQ limits its clinical application. Thus, a novel phytosomal delivery system of TQ-Phospholipon® 90H complex (TQ-phytosome) was developed by refluxing combined with anti-solvent precipitation. This TQ delivery system was optimized by a three-factor, three-level Box-Behnken design. The optimized TQ-phytosome size was (45.59 ± 1.82 nm) and the vesicle size was confirmed by transmission electron microscopy. The in vitro release pattern of the formulation indicated a biphasic release pattern, where an initial burst release was observed within 2 h, followed by a prolonged release. A remarkable increase in dose-dependent cytotoxicity was evident from the significant decrease in IC50 value of TQ-phytosomes (4.31 ± 2.21 µM) against the A549 cell line. The differential effect of TQ-phytosomes in cell cycle analysis was observed, where cancer cells were accumulated on G2-M and pre-G1 phases. Furthermore, increased apoptotic induction and cell necrosis of TQ-phytosomes were revealed with the annexin V staining technique via activation of caspase-3. In reactive oxygen species (ROS) analysis, TQ-phytosomes acted to significantly increase ROS generation in A549 cells. In conclusion, the sustained release profile with significantly-improved anticancer potential could be obtained with TQ by this phytosomal nanocarrier platform.

ACS Style

Nabil Alhakamy; Shaimaa Badr-Eldin; Usama A. Fahmy; Nabil Alruwaili; Zuhier Awan; Giuseppe Caruso; Mohamed Alfaleh; Ahmed Alaofi; Faris Arif; Osama Ahmed; Adel Alghaith. Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells. Pharmaceutics 2020, 12, 761 .

AMA Style

Nabil Alhakamy, Shaimaa Badr-Eldin, Usama A. Fahmy, Nabil Alruwaili, Zuhier Awan, Giuseppe Caruso, Mohamed Alfaleh, Ahmed Alaofi, Faris Arif, Osama Ahmed, Adel Alghaith. Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells. Pharmaceutics. 2020; 12 (8):761.

Chicago/Turabian Style

Nabil Alhakamy; Shaimaa Badr-Eldin; Usama A. Fahmy; Nabil Alruwaili; Zuhier Awan; Giuseppe Caruso; Mohamed Alfaleh; Ahmed Alaofi; Faris Arif; Osama Ahmed; Adel Alghaith. 2020. "Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells." Pharmaceutics 12, no. 8: 761.

Journal article
Published: 15 July 2020 in Pharmaceuticals
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Naringenin (NAR), a flavonoid mainly found in citrus and grapefruits, has proven anti-cancer activities. However, the poor water solubility and low bioavailability of NAR limits its use as a therapeutic agent. The aim of this study was to develop and optimize stable naringenin nanoemulsions (NAR-NE) using a Box–Behnken experimental design to obtain a formulation with a higher efficiency. Anticancer activity of optimized NAR-NE was evaluated in A549 lung cancer cells using cell viability, flow-cytometric assays, and enzyme-linked immunosorbent assay. The stabilized nanoemulsion, which showed a spherical surface morphology, had a globule size of 85.6 ± 2.1 nm, a polydispersity index of 0.263 ± 0.02, a zeta potential of −9.6 ± 1.2 mV, and a drug content of 97.34 ± 1.3%. The NAR release from the nanoemulsion showed an initial burst release followed by a stable and controlled release for a longer period of 24 h. The nanoemulsion exhibited excellent thermodynamic and physical stability against phase separation and storage. The NAR-NE showed concentration-dependent cytotoxicity in A549 lung cancer cells, which was greater than that of free NAR. The percentage of apoptotic cells and cell cycle arrest at the G2/M and pre-G1 phases induced by NAR-NE were significantly higher than those produced by free NAR (p < 0.05). NAR-NEs were more effective than the NAR solution in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. Therefore, stabilized NAR-NE could be a suitable drug delivery system to enhance the effects of NAR in the treatment of lung cancer.

ACS Style

Shadab; Nabil A. Alhakamy; Hibah M. Aldawsari; Mohammad Husain; Sabna Kotta; Samaa T. Abdullah; Usama A. Fahmy; Mohamed A. AlFaleh; Hani Z. Asfour. Formulation Design, Statistical Optimization, and In Vitro Evaluation of a Naringenin Nanoemulsion to Enhance Apoptotic Activity in A549 Lung Cancer Cells. Pharmaceuticals 2020, 13, 152 .

AMA Style

Shadab, Nabil A. Alhakamy, Hibah M. Aldawsari, Mohammad Husain, Sabna Kotta, Samaa T. Abdullah, Usama A. Fahmy, Mohamed A. AlFaleh, Hani Z. Asfour. Formulation Design, Statistical Optimization, and In Vitro Evaluation of a Naringenin Nanoemulsion to Enhance Apoptotic Activity in A549 Lung Cancer Cells. Pharmaceuticals. 2020; 13 (7):152.

Chicago/Turabian Style

Shadab; Nabil A. Alhakamy; Hibah M. Aldawsari; Mohammad Husain; Sabna Kotta; Samaa T. Abdullah; Usama A. Fahmy; Mohamed A. AlFaleh; Hani Z. Asfour. 2020. "Formulation Design, Statistical Optimization, and In Vitro Evaluation of a Naringenin Nanoemulsion to Enhance Apoptotic Activity in A549 Lung Cancer Cells." Pharmaceuticals 13, no. 7: 152.

Preprint
Published: 02 July 2020
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As the coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2, continues to spread rapidly around the world, there is a need for well validated serological assays that allow the detection of viral specific antibody responses in COVID-19 patients or recovered individuals. In this study, we established and used multiple indirect Enzyme Linked Immunosorbent Assay (ELISA)-based serological assays to study the antibody response in COVID-19 patients. In order to validate the assays we determined the cut off values, sensitivity and specificity of the assays using sera collected from pre-pandemic healthy controls, COVID-19 patients at different time points after disease-onset, and seropositive sera to other human coronaviruses. The developed SARS-CoV-2 S1 subunit of the spike glycoprotein and nucleocapsid (N)-based ELISAs not only showed high specificity and sensitivity but also did not show any cross-reactivity with other CoVs. We also show that all RT-PCR confirmed COVID-19 patients tested in our study developed both virus specific IgM and IgG antibodies as early as week one after disease onset. Our data also suggest that the inclusion of both S1 and N in serological testing would capture as many potential SARS-CoV-2 positive cases as possible than using any of them alone. This is specifically important for tracing contacts and cases and conducting large-scale epidemiological studies to understand the true extent of virus spread in populations.

ACS Style

Abdullah Algaissi; Mohamed A. AlFaleh; Sherif Hala; Turki S. Abujamel; Sawsan S. Alamri; Sarah A Almahboub; Khalid A. Alluhaybi; Haya I. Hobani; Reem M. Alsulaiman; Rahaf H. Alharbi; M-Zaki El-Assouli; Rowa Y Alhabbab; Ahdab A. AlSaieedi; Wesam H. Abdulaal; Afrah A. Al-Somali; Fadwa S. Alofi; Asim A. Khogeer; Ahmad Bakur Mahmoud; Almohanad A Alkayyal; Naif A.M. Almontashiri; Arnab Pain; Anwar M. Hashem. SARS-CoV-2 S1 and N-Based Serological Assays Reveal Rapid Seroconversion and Induction of Specific Antibody Response in COVID-19 Patients. 2020, 1 .

AMA Style

Abdullah Algaissi, Mohamed A. AlFaleh, Sherif Hala, Turki S. Abujamel, Sawsan S. Alamri, Sarah A Almahboub, Khalid A. Alluhaybi, Haya I. Hobani, Reem M. Alsulaiman, Rahaf H. Alharbi, M-Zaki El-Assouli, Rowa Y Alhabbab, Ahdab A. AlSaieedi, Wesam H. Abdulaal, Afrah A. Al-Somali, Fadwa S. Alofi, Asim A. Khogeer, Ahmad Bakur Mahmoud, Almohanad A Alkayyal, Naif A.M. Almontashiri, Arnab Pain, Anwar M. Hashem. SARS-CoV-2 S1 and N-Based Serological Assays Reveal Rapid Seroconversion and Induction of Specific Antibody Response in COVID-19 Patients. . 2020; ():1.

Chicago/Turabian Style

Abdullah Algaissi; Mohamed A. AlFaleh; Sherif Hala; Turki S. Abujamel; Sawsan S. Alamri; Sarah A Almahboub; Khalid A. Alluhaybi; Haya I. Hobani; Reem M. Alsulaiman; Rahaf H. Alharbi; M-Zaki El-Assouli; Rowa Y Alhabbab; Ahdab A. AlSaieedi; Wesam H. Abdulaal; Afrah A. Al-Somali; Fadwa S. Alofi; Asim A. Khogeer; Ahmad Bakur Mahmoud; Almohanad A Alkayyal; Naif A.M. Almontashiri; Arnab Pain; Anwar M. Hashem. 2020. "SARS-CoV-2 S1 and N-Based Serological Assays Reveal Rapid Seroconversion and Induction of Specific Antibody Response in COVID-19 Patients." , no. : 1.

Journal article
Published: 01 July 2020 in Journal of Pharmaceutical Sciences
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Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator and Vitamin D (Vit.D) is an important fat-soluble vitamin usually administrated concurrently to treat postmenopausal osteoporosis. Both drugs have low bioavailability due to absorption problems associated with low solubility. The aim of this research was to combine the 2 drugs in nanostructure lipid carriers (NLCs) in order to overcome the previously mentioned drawbacks. Face centered central composite design combined with relative weight-based desirability index was used to optimize RLX-Vit.D-NLCs and investigate the effect of independent variables on NLCs size, entrapment, dissolution, and permeation efficiencies. Pharmacokinetic parameters of optimized NLCs were tested in healthy human volunteers. The results showed that NLCs obtained at 9.37:1 lipid/drug ratio, 1.35:4 Sefsol 218/Glyceryl monostearate ratio and 2.25% Cremophor were 98 nm bearing 82.7% and 57.3% of RLX, and Vit.D, respectively. These nanocarriers enhanced RLX bioavailability by 385.6% relative to commercial product. The level of Vit.D metabolite was significantly increased from an average baseline level of 91 ± 29 nmol/L to 174 ± 36 nmol/L. High level correlation was found between fractions of RLX absorbed and dissolved. Significant improvement of RLX and Vit.D bioavailability through encapsulation within NLCs encourages its use in the treatment of postmenopausal osteoporosis compared to commercialized products.

ACS Style

Khaled M. Hosny; Rahaf H. Bahmdan; Nabil Alhakamy; Mohamed A. Alfaleh; Osama A. Ahmed; Mohammed H. Elkomy. Physically Optimized Nano-Lipid Carriers Augment Raloxifene and Vitamin D Oral Bioavailability in Healthy Humans for Management of Osteoporosis. Journal of Pharmaceutical Sciences 2020, 109, 2145 -2155.

AMA Style

Khaled M. Hosny, Rahaf H. Bahmdan, Nabil Alhakamy, Mohamed A. Alfaleh, Osama A. Ahmed, Mohammed H. Elkomy. Physically Optimized Nano-Lipid Carriers Augment Raloxifene and Vitamin D Oral Bioavailability in Healthy Humans for Management of Osteoporosis. Journal of Pharmaceutical Sciences. 2020; 109 (7):2145-2155.

Chicago/Turabian Style

Khaled M. Hosny; Rahaf H. Bahmdan; Nabil Alhakamy; Mohamed A. Alfaleh; Osama A. Ahmed; Mohammed H. Elkomy. 2020. "Physically Optimized Nano-Lipid Carriers Augment Raloxifene and Vitamin D Oral Bioavailability in Healthy Humans for Management of Osteoporosis." Journal of Pharmaceutical Sciences 109, no. 7: 2145-2155.

Preprint
Published: 23 May 2020
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Emerging highly pathogenic human coronaviruses (CoVs) represent a serious ongoing threat to the public health worldwide. The spike (S) proteins of CoVs are surface glycoproteins that facilitate viral entry into host cells via attachment to their respective cellular receptors. The S protein is believed to be a major immunogenic component of CoVs and a target for neutralizing antibodies (nAbs) and most candidate vaccines. Development of a safe and convenient assay is thus urgently needed to determine the prevalence of CoVs nAbs in the population, to study immune response in infected individuals, and to aid in vaccines and viral entry inhibitors evaluation. While live virus-based neutralization assays are used as gold standard serological methods to detect and measure nAbs, handling of highly pathogenic live CoVs requires strict bio-containment conditions in biosafety level-3 laboratories. On the other hand, use of replication-incompetent pseudoviruses bearing CoVs S proteins could represent a safe and useful method to detect nAbs in serum samples under biosafety level-2 conditions. Here, we describe a detailed protocol of a safe and convenient assay to generate vesicular stomatitis virus (VSV)-based pseudoviruses to evaluate and measure nAbs against highly pathogenic CoVs. The protocol covers methods to produce VSV pseudovirus bearing the S protein of the Middle East respiratory syndrome-CoV (MERS-CoV) and the severe acute respiratory syndrome-CoV-2 (SARS-CoV-2), pseudovirus titration, and pseudovirus neutralizing assay. Such assay could be adapted by different laboratories and researchers working on highly pathogenic CoVs without the need to handle live viruses in biosafety level-3 environment.

ACS Style

Sarah A. Almahboub; Abdullah Algaissi; Mohamed A. AlFaleh; M-Zaki ElAssouli; Anwar M. Hashem. Evaluation of Neutralizing Antibodies against Highly Pathogenic Coronaviruses: A Detailed Protocol for a Rapid Evaluation of Neutralizing Antibodies Using Vesicular Stomatitis Virus (Vsv) Pseudovirus-Based Assay. 2020, 1 .

AMA Style

Sarah A. Almahboub, Abdullah Algaissi, Mohamed A. AlFaleh, M-Zaki ElAssouli, Anwar M. Hashem. Evaluation of Neutralizing Antibodies against Highly Pathogenic Coronaviruses: A Detailed Protocol for a Rapid Evaluation of Neutralizing Antibodies Using Vesicular Stomatitis Virus (Vsv) Pseudovirus-Based Assay. . 2020; ():1.

Chicago/Turabian Style

Sarah A. Almahboub; Abdullah Algaissi; Mohamed A. AlFaleh; M-Zaki ElAssouli; Anwar M. Hashem. 2020. "Evaluation of Neutralizing Antibodies against Highly Pathogenic Coronaviruses: A Detailed Protocol for a Rapid Evaluation of Neutralizing Antibodies Using Vesicular Stomatitis Virus (Vsv) Pseudovirus-Based Assay." , no. : 1.

Review article
Published: 06 May 2020 in Travel Medicine and Infectious Disease
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The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.

ACS Style

Anwar M. Hashem; Badrah S. Alghamdi; Abdullah A. Algaissi; Fahad S. Alshehri; Abdullah Bukhari; Mohamed Alfaleh; Ziad A. Memish. Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review. Travel Medicine and Infectious Disease 2020, 35, 101735 -101735.

AMA Style

Anwar M. Hashem, Badrah S. Alghamdi, Abdullah A. Algaissi, Fahad S. Alshehri, Abdullah Bukhari, Mohamed Alfaleh, Ziad A. Memish. Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review. Travel Medicine and Infectious Disease. 2020; 35 ():101735-101735.

Chicago/Turabian Style

Anwar M. Hashem; Badrah S. Alghamdi; Abdullah A. Algaissi; Fahad S. Alshehri; Abdullah Bukhari; Mohamed Alfaleh; Ziad A. Memish. 2020. "Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review." Travel Medicine and Infectious Disease 35, no. : 101735-101735.

Original research
Published: 01 April 2020 in International Journal of Nanomedicine
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Background: Peptic ulcer disease, a painful lesion of the gastric mucosa, is considered one of the most common gastrointestinal disorders. This study aims to investigate the formulation of pumpkin seed oil (PSO)-based nanostructured lipid carriers (NLCs) to utilize PSO as the liquid lipid component of NLCs and to achieve oil dispersion in the nano-range in the stomach. Methods: Box–Behnken design was utilized to deduce the optimum formula with minimum particle size. The optimized PSO-NLCs formula was investigated for gastric ulcer protective effects in Wistar rats by evaluating ulcer index and determination of gastric mucosa oxidative stress parameters. Results: PSO was successfully incorporated as the liquid lipid (LL) component of NLCs. The prepared optimum PSO-NLCs formula showed a size of 64.3 nm. Pretreatment of animals using the optimized PSO-NLCs formula showed significantly (p< 0.001) lower ulcer index compared to indomethacin alone group and significantly (p< 0.05) less mucosal lesions compared to the raw oil. Conclusion: These results indicated great potential for future application of optimized PSO-NLCs formula for antiulcer effect in non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer.

ACS Style

Osama Aa Ahmed; Usama Ahmed Fahmy; Rana Bakhaidar; Mohamed A El-Moselhy; Mohamed A Alfaleh; Al-Shaimaa F Ahmed; Asmaa Sa Hammad; Hibah Aldawsari; Nabil A Alhakamy. Pumpkin Oil–Based Nanostructured Lipid Carrier System for Antiulcer Effect in NSAID-Induced Gastric Ulcer Model in Rats. International Journal of Nanomedicine 2020, ume 15, 2529 -2539.

AMA Style

Osama Aa Ahmed, Usama Ahmed Fahmy, Rana Bakhaidar, Mohamed A El-Moselhy, Mohamed A Alfaleh, Al-Shaimaa F Ahmed, Asmaa Sa Hammad, Hibah Aldawsari, Nabil A Alhakamy. Pumpkin Oil–Based Nanostructured Lipid Carrier System for Antiulcer Effect in NSAID-Induced Gastric Ulcer Model in Rats. International Journal of Nanomedicine. 2020; ume 15 ():2529-2539.

Chicago/Turabian Style

Osama Aa Ahmed; Usama Ahmed Fahmy; Rana Bakhaidar; Mohamed A El-Moselhy; Mohamed A Alfaleh; Al-Shaimaa F Ahmed; Asmaa Sa Hammad; Hibah Aldawsari; Nabil A Alhakamy. 2020. "Pumpkin Oil–Based Nanostructured Lipid Carrier System for Antiulcer Effect in NSAID-Induced Gastric Ulcer Model in Rats." International Journal of Nanomedicine ume 15, no. : 2529-2539.

Journal article
Published: 09 March 2020 in International Journal of Pharmaceutics
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Successful gene therapy requires the development of vectors that enable efficient delivery of genetic materials (e.g., pDNA or siRNA) to targeted cells, without degradation of the genetic materials. We have shown that nanoparticles formed by combining cell-penetrating peptide and pDNA (CPP-pDNA) into complexes and condensing them with calcium chloride can provide gene nanoparticles with high transfection efficiency and low cytotoxicity. In this work, we compare in situ measurements of the membrane insertion potential of three arginine-based gene nanoparticles (RW9-NPs, R9-NPs, and RH9-NPs) using four lipid compositions and two types of model membrane (Langmuir monolayers vs. supported bilayers) with their transfection efficiency in two human cancer cell lines. Using a Langmuir trough, we measured the membrane insertion potential of our gene nanoparticles to model membrane monolayers. A Quartz Crystal Microbalance with Dissipation (QCM-D) technique was used to monitor the adsorption of these nanoparticles to lipid bilayers of various compositions. Finally, gene expression using these nanoparticles was measured in breast cancer and cervical cancer cell lines. Our cell culture studies indicate that although R9-NPs and RW9-NPs show a significant increase in transfection efficiency compared to free pDNA, RH9-NPs do not show any significant difference. Both the Langmuir monolayer and QCM-D bilayer studies show that these results are best reflected in the in situ measurement assays when lipid systems containing a mixture of phospholipids, cholesterol, and sphingolipids are used. It is important to note that the mechanism of penetration is expected to differ for RW9 vs. R9; however, gene nanoparticles containing either of these CPPs show similar transfection efficiency. Our results therefore demonstrate that the design of predictive assays for gene therapy using CPPs must involve carefully chosen model lipid membrane systems that accurately represent the varying compositions of cell membranes.

ACS Style

Nabil A. Alhakamy; Ahmed L. Alaofi; Osama Ahmed; Usama Ahmed Fahmy; Shadab; Wesam H. Abdulaal; Mohamed A. Alfaleh; Aishik Chakraborty; Cory J. Berkland; Prajnaparamita Dhar. Development of lipid membrane based assays to accurately predict the transfection efficiency of cell-penetrating peptide-based gene nanoparticles. International Journal of Pharmaceutics 2020, 580, 119221 .

AMA Style

Nabil A. Alhakamy, Ahmed L. Alaofi, Osama Ahmed, Usama Ahmed Fahmy, Shadab, Wesam H. Abdulaal, Mohamed A. Alfaleh, Aishik Chakraborty, Cory J. Berkland, Prajnaparamita Dhar. Development of lipid membrane based assays to accurately predict the transfection efficiency of cell-penetrating peptide-based gene nanoparticles. International Journal of Pharmaceutics. 2020; 580 ():119221.

Chicago/Turabian Style

Nabil A. Alhakamy; Ahmed L. Alaofi; Osama Ahmed; Usama Ahmed Fahmy; Shadab; Wesam H. Abdulaal; Mohamed A. Alfaleh; Aishik Chakraborty; Cory J. Berkland; Prajnaparamita Dhar. 2020. "Development of lipid membrane based assays to accurately predict the transfection efficiency of cell-penetrating peptide-based gene nanoparticles." International Journal of Pharmaceutics 580, no. : 119221.

Articles
Published: 17 December 2019 in Pharmaceutical Development and Technology
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Febuxostat (FBX) is used to treat gout and chronic hyperuricemia. However, its bioavailability is moderate (49%) as a result of low solubility and first pass metabolism. Therefore, the aim of our study is to improve FBX bioavailability by enhancement its solubility using self-nanoemulsifying drug delivery system (SNEDDS) technique in the form of transdermal film to avoid hepatic metabolism. To accomplish this goal, Eight SNEDDS formulae were prepared according to a three-factor, two level D-Optimal mixture design to evaluate the effect of different ratios of the Lemon oil (X1), the surfactant Tween-20 (X2), and the co-surfactant PEG-400 (X3) on the globule size in order to reach smallest globular size. Results revealed that SNEDDS globule size ranged from 177 to 454 nm. The optimized formula consisted of 20% oil, 40% surfactant and 40% co-surfactant. Diffusion study showed improved enhancement in skin permeation that was confirmed by imaging using fluorescence microscope. In vivo plasma data showed significant (p< 0-05) difference in FBX plasma levels and pharmacokinetic parameters when compared with raw FBX loaded film. In conclusion, FBX-SNEDDS loaded transdermal film could be a successful way to improve solubility and skin permeability that would lead to improvement in patient's compliance.

ACS Style

Nabil A. Alhakamy; Usama A. Fahmy; Osama A. A. Ahmed; Enas A. Almohammadi; Shahad A. Alotaibi; Raghad A. Aljohani; Waleed S. Alharbi; Mohamed A. AlFaleh; Mohammad Y. Alfaifi. Development of an optimized febuxostat self-nanoemulsified loaded transdermal film: in-vitro, ex-vivo and in-vivo evaluation. Pharmaceutical Development and Technology 2019, 25, 326 -331.

AMA Style

Nabil A. Alhakamy, Usama A. Fahmy, Osama A. A. Ahmed, Enas A. Almohammadi, Shahad A. Alotaibi, Raghad A. Aljohani, Waleed S. Alharbi, Mohamed A. AlFaleh, Mohammad Y. Alfaifi. Development of an optimized febuxostat self-nanoemulsified loaded transdermal film: in-vitro, ex-vivo and in-vivo evaluation. Pharmaceutical Development and Technology. 2019; 25 (3):326-331.

Chicago/Turabian Style

Nabil A. Alhakamy; Usama A. Fahmy; Osama A. A. Ahmed; Enas A. Almohammadi; Shahad A. Alotaibi; Raghad A. Aljohani; Waleed S. Alharbi; Mohamed A. AlFaleh; Mohammad Y. Alfaifi. 2019. "Development of an optimized febuxostat self-nanoemulsified loaded transdermal film: in-vitro, ex-vivo and in-vivo evaluation." Pharmaceutical Development and Technology 25, no. 3: 326-331.

Journal article
Published: 12 February 2019 in Antibodies
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CD117 (c-Kit) is a tyrosine kinase receptor that is overexpressed in multiple dog tumors. There is 100% homology between the juxtamembrane domain of human and canine CD117, and many cancer-causing mutations occur in this region in both species. Thus, CD117 is an important target for cancer treatment in dogs and for comparative oncology studies. Currently, there is no monoclonal antibody (mAb) specifically designed to target the exposed region of canine CD117, although there exist some with species cross-reactivity. We panned a naïve phage display library to isolate antibodies against recombinant CD117 on whole cells. Several mAbs were isolated and were shown to bind recombinant canine CD117 at low- to sub-nanomolar affinity. Additionally, binding to native canine CD117 was confirmed by immunohistochemistry and by flow cytometry. Competitive binding assays also identified mAbs that competed with the CD117 receptor-specific ligand, the stem cell factor (SCF). These results show the ability of our cell-based biopanning strategy to isolate a panel of antibodies that have varied characteristics when used in different binding assays. These in vitro/ex vivo assessments suggest that some of the isolated mAbs might be promising candidates for targeting overexpressed CD117 in canine cancers for different useful applications.

ACS Style

Mohamed A. AlFaleh; Neetika Arora; Michael Yeh; Christopher de Bakker; Christopher B. Howard; Philip MacPherson; Rachel E. Allavena; Xiaoli Chen; Linda Harkness; Stephen M. Mahler; Martina L. Jones. Canine CD117-Specific Antibodies with Diverse Binding Properties Isolated from a Phage Display Library Using Cell-Based Biopanning. Antibodies 2019, 8, 15 .

AMA Style

Mohamed A. AlFaleh, Neetika Arora, Michael Yeh, Christopher de Bakker, Christopher B. Howard, Philip MacPherson, Rachel E. Allavena, Xiaoli Chen, Linda Harkness, Stephen M. Mahler, Martina L. Jones. Canine CD117-Specific Antibodies with Diverse Binding Properties Isolated from a Phage Display Library Using Cell-Based Biopanning. Antibodies. 2019; 8 (1):15.

Chicago/Turabian Style

Mohamed A. AlFaleh; Neetika Arora; Michael Yeh; Christopher de Bakker; Christopher B. Howard; Philip MacPherson; Rachel E. Allavena; Xiaoli Chen; Linda Harkness; Stephen M. Mahler; Martina L. Jones. 2019. "Canine CD117-Specific Antibodies with Diverse Binding Properties Isolated from a Phage Display Library Using Cell-Based Biopanning." Antibodies 8, no. 1: 15.

Research article
Published: 23 October 2017 in PLOS ONE
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Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV) are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs) which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN). Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.

ACS Style

Mohamed Alfaleh; Christopher B. Howard; Ilya Sedliarou; Martina L. Jones; Reema Gudhka; Natasha Vanegas; Jocelyn Weiss; Julia H. Suurbach; Christopher de Bakker; Michael R. Milne; Bree A. Rumballe; Jennifer A. MacDiarmid; Himanshu Brahmbhatt; Stephen Mahler. Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models. PLOS ONE 2017, 12, e0186137 -e0186137.

AMA Style

Mohamed Alfaleh, Christopher B. Howard, Ilya Sedliarou, Martina L. Jones, Reema Gudhka, Natasha Vanegas, Jocelyn Weiss, Julia H. Suurbach, Christopher de Bakker, Michael R. Milne, Bree A. Rumballe, Jennifer A. MacDiarmid, Himanshu Brahmbhatt, Stephen Mahler. Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models. PLOS ONE. 2017; 12 (10):e0186137-e0186137.

Chicago/Turabian Style

Mohamed Alfaleh; Christopher B. Howard; Ilya Sedliarou; Martina L. Jones; Reema Gudhka; Natasha Vanegas; Jocelyn Weiss; Julia H. Suurbach; Christopher de Bakker; Michael R. Milne; Bree A. Rumballe; Jennifer A. MacDiarmid; Himanshu Brahmbhatt; Stephen Mahler. 2017. "Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models." PLOS ONE 12, no. 10: e0186137-e0186137.

Review
Published: 05 August 2017 in Antibodies
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Membrane proteins are attractive targets for monoclonal antibody (mAb) discovery and development. Although several approved mAbs against membrane proteins have been isolated from phage antibody libraries, the process is challenging, as it requires the presentation of a correctly folded protein to screen the antibody library. Cell-based panning could represent the optimal method for antibody discovery against membrane proteins, since it allows for presentation in their natural conformation along with the appropriate post-translational modifications. Nevertheless, screening antibodies against a desired antigen, within a selected cell line, may be difficult due to the abundance of irrelevant organic molecules, which can potentially obscure the antigen of interest. This review will provide a comprehensive overview of the different cell-based phage panning strategies, with an emphasis placed on the optimisation of four critical panning conditions: cell surface antigen presentation, non-specific binding events, incubation time, and temperature and recovery of phage binders.

ACS Style

Mohamed A. Alfaleh; Martina L. Jones; Christopher B. Howard; Stephen M. Mahler. Strategies for Selecting Membrane Protein-Specific Antibodies using Phage Display with Cell-Based Panning. Antibodies 2017, 6, 10 .

AMA Style

Mohamed A. Alfaleh, Martina L. Jones, Christopher B. Howard, Stephen M. Mahler. Strategies for Selecting Membrane Protein-Specific Antibodies using Phage Display with Cell-Based Panning. Antibodies. 2017; 6 (3):10.

Chicago/Turabian Style

Mohamed A. Alfaleh; Martina L. Jones; Christopher B. Howard; Stephen M. Mahler. 2017. "Strategies for Selecting Membrane Protein-Specific Antibodies using Phage Display with Cell-Based Panning." Antibodies 6, no. 3: 10.