Publications

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2018
Saber, M. M., A. M. Al-mahallawi, N. N. Nassar, B. Stork, and S. A. Shouman, "Targeting colorectal cancer cell metabolism through development of cisplatin and metformin nano-cubosomes.", BMC cancer, vol. 18, issue 1, pp. 822, 2018 Aug 15. Abstract

BACKGROUND: Colorectal cancer (CRC) remains a leading cause of death worldwide. Utilizing cisplatin in CRC is correlated with severe adverse effects and drug-resistance. Combined anticancer drug-treatment, along with, their enhanced delivery, can effectively kill cancer through multiple pathways. Nano-cubosomes are emerging as nanocarriers for anticancer therapies, hence, we constructed nano-cubosomes bearing cisplatin and cisplatin-metformin combination for investigation on HCT-116 cells.

METHODS: Nano-cubosomes bearing either cisplatin alone or cisplatin-metformin combination were formulated using emulsification technique. The loaded nano-cubosomes were characterized in vitro and the optimized formulation was selected. Their cytotoxic effects were investigated by Sulphorhodamine-B (SRB) assay. The AMPK/mTOR metabolic pathway as well as the Akt/mTOR pathway were analyzed using ELISA technique. Colorimetry was used in NADPH oxidase, LDH and caspase-3 activity determination.

RESULTS: nano-cubosomal formulations exhibited superior cytotoxic effect compared to unformulated cisplatin. This cytotoxic effect was profound upon incorporation of metformin, an indirect mTOR inhibitor, in cisplatin nano-cubosomes. The induced CRC cell apoptosis was through inhibition of several metabolic pathways, namely, AMPK/mTOR and Akt/mTOR. Drug-loaded nano-cubosomes ensued depletion in glucose and energy levels that led to AMPK activation and thus mTOR inhibition. mTOR was additionally inhibited via suppression of p-Akt (Ser473) levels after nano-cubosomal treatment. Moreover, drug-loaded nano-cubosomes produced a notable escalation in ROS levels, evident as an increase in NADPH oxidase, inhibition of LDH and a consequential upsurge in caspase-3.

CONCLUSION: These results demonstrated the influence exerted by cisplatin-loaded nano-cubosomes on CRC cell survival and enhancement of their cytotoxicity upon metformin addition.

2017
Farrag, N. S., H. A. El-Sabagh, A. M. Al-mahallawi, A. M. Amin, A. A. El-bary, and W. Mamdouh, "Comparative study on radiolabeling and biodistribution of core-shell silver/polymeric nanoparticles-based theranostics for tumor targeting.", International journal of pharmaceutics, vol. 529, issue 1-2, pp. 123-133, 2017 Aug 30. Abstract

A simple and rapid method for radiolabeling of three types of Ag NPs has been performed using (125)I isotope, with high labeling yields, >90% without disturbing the optical properties. All the factors affecting labeling yield were studied. In order to monitor the in-vivo tissue uptake of radiolabeled Ag NPs using γ-rays, Ag-based radioiodo-NPs with a maximum labeling yield were intravenously injected in normal and solid tumor bearing mice. The preliminary biodistribution study revealed that this new radioiodo-NPs have a high affinity to be localized in the tumor site for a long period of time. The reported highly efficient method provides new radiolabeled Ag-based NPs as tumor-specific agents for both diagnostic and therapeutic applications.

Al-mahallawi, A. M., O. M. Khowessah, and R. A. Shoukri, "Enhanced non invasive trans-tympanic delivery of ciprofloxacin through encapsulation into nano-spanlastic vesicles: Fabrication, in-vitro characterization, and comparative ex-vivo permeation studies.", International journal of pharmaceutics, vol. 522, issue 1-2, pp. 157-164, 2017 Apr 30. Abstract

The aim of this research was to encapsulate ciprofloxacin, a broad spectrum fluoroquinolone antibiotic, into Span 60 based nano-elastic vesicles, nano-spanlastics, for accomplishing improved non invasive trans-tympanic delivery, providing means for ototopical treatment of acute otitis media (AOM). To achieve this purpose, ciprofloxacin-loaded nano-spanlastics were prepared by thin film hydration (TFH) technique, using several non-ionic edge activators (EAs) according to full factorial design (3(2)). The investigation of the effect of formulation variables on nano-spanlastic characteristics and selection of the optimum formula were performed using Design-Expert(®) software. The selected formulation was also subjected to comparative ex-vivo permeation studies through tympanic membrane (TM) of rabbits. Results revealed that the optimal nano-spanlastic formulation (S-2; containing 20% Brij 35 as an EA) exhibited nano-sized spherical vesicles (287.55±9.97nm), relatively high entrapment efficiency percent (51.81±1.57%), and good physical stability after six months of storage at 4-8°C. Ex-vivo TM permeation studies demonstrated the superiority of the optimal nano-spanlastic formulation over the commercial Ciprocin(®) drops. However, when compared to lipid-based elastic vesicles, nano-transfersomes, nano-spanlastics exhibited lower drug permeation through the TM. Concisely, the obtained results suggested that nano-spanlastics can be promising for improving trans-tympanic delivery of ciprofloxacin.

2016
Abdelbary, A. A., W. H. Abd-Elsalam, and A. M. Al-mahallawi, "Fabrication of novel ultradeformable bilosomes for enhanced ocular delivery of terconazole: In vitro characterization, ex vivo permeation and in vivo safety assessment.", International journal of pharmaceutics, vol. 513, issue 1-2, pp. 688-696, 2016 Nov 20. Abstract

The objective of this work was to encapsulate terconazole (TCZ), a water insoluble antifungal drug, into novel ultradeformable bilosomes (UBs) for achieving enhanced ocular delivery. In addition to the constituents of the conventional bilosomes; namely, Span 60, cholesterol, and the bile salts, UBs contain an edge activator which imparts extra elasticity to the vesicles and consequently hypothesized to result in improved corneal permeation. In this study, TCZ loaded UBs were prepared utilizing ethanol injection method according to 2(3) full factorial design. The investigation of the influence of different formulation variables on UBs properties and selection of the optimum formulation was done using Design-Expert(®) software. The selected UBs formulation (UB1; containing 10mg bile salt and 5mg Cremophor EL as an edge activator) showed nanosized spherical vesicles (273.15±2.90nm) and high entrapment efficiency percent (95.47±2.57%). Results also revealed that the optimum UBs formulation exhibited superior ex vivo drug flux through rabbit cornea when compared with conventional bilosomes, niosomes, and drug suspension. Furthermore, in vivo ocular tolerance and histopathological studies conducted using male albino rabbits proved the safety of the fabricated UBs after topical ocular application. Overall, the obtained results confirmed that UBs could be promising for ocular drug delivery.

2015
Al-mahallawi, A. M., A. A. Abdelbary, and M. H. Aburahma, "Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam", International Journal of Pharmaceutics, vol. 485, pp. 329-340, 2015.
Abdelbary, A. A., A. M. Al-mahallawi, M. E. Abdelrahim, and A. M. A. Ali, "Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration", International Journal of Nanomedicine, vol. 10, pp. 6339–6353, 2015.
2014
Al-mahallawi, A. M., O. M. Khowessah, and R. A. Shoukri, "Ciprofloxacin-loaded Spanlastics for Ototopical Non-invasive Delivery to the Middle Ear: In-vitro and Ex-vivo Studies", Inventi Impact: NDDS, vol. 2014, issue 3, 2014.
Al-mahallawi, A. M., O. M. Khowessah, and R. A. Shoukri, "Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: In-vitro optimization, ex-vivo permeation studies, and in-vivo assessment", International journal of pharmaceutics, vol. 472, pp. 304-314, 2014.
2012
Al-mahallawi, A. M., O. M. Khowessah, and R. A. Shoukri, "Novel Sustained Release Orally Disintegrating Tablet Containing Aceclofenac Lipospheres: In-vitro and In-vivo Studies", Inventi Impact: Pharm Tech, vol. 2012, issue 2, 2012. Website
Al-mahallawi, A. M., O. M. Khowessah, and R. A. Shoukri, "OPTIMIZATION OF ACECLOFENAC ONCE DAILY MATRIX TABLETS: IN-VITRO AND IN-VIVO STUDIES", JOURNAL OF PHARMACEUTICAL RESEARCH AND OPINION (JPRO), vol. 2, issue 1, pp. 12-22, 2012.
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