Kotta, S., V. K. A. Shirin, R. Sankar, S. M. Badr-Eldin, H. M. Aldawsari, N. A. Alhakamy, and P. K, "Nutraceuticals for alzheimer's disease", Bioactive Nutraceuticals for Brain Disorders: Nova Science Publishers, Inc., 2021. Abstract

Nutraceuticals are compounds of mainly plant origin and are found applicable for the therapy of a largenumber of diseases. They possess important pharmacological actions such as anti-inflammatory,antioxidant, and neuroprotectiveactivities. Alzheimer's disease (AD) is a neurodegenerative disordermostly found in aged groups and is connected with the amyloid-beta peptide and neurofibrillary tangleformation. Even though many drugs are available for the treatment, a complete cure for this disease isnot yet available. This highlights the importance of dietary and lifestyle habits for disease modification.Many compounds of plant origin have been identified to possess potent activity against the development of AD. These nutraceuticals can play major roles in different stages through different molecular targets of AD both in neuronal as well as biochemical levels. These substances have morethan one mechanism in controlling various signaling pathways in the pathogenesis of AD. The chapter gives a detailed description of nutraceuticals that have been explored to date for their beneficiary role in AD. The intake of these food supplements can provide significant benefits in AD as evidenced by different in vitro and in vivo experiments. The food mentioned in this chapter is a proven remedy against AD. So the inclusion of these agents in the daily diet will produce a positive impact on thisneurodegenerative disease of the elderly

Badr-Eldin, S. M., H. M. Aldawsari, S. Kotta, and N. A. Alhakamy, "Self-Assembled Supramolecular Hydrogel Based on α-Cyclodextrin/Poloxamer Polypseudorotaxanes for Ocular Delivery of Ciprofloxacin", International Journal of Pharmacology, vol. 17, issue 1, pp. 15-27, 2021.
Badr-Eldin, S. M., N. A. Alhakamy, U. A. Fahmy, O. A. A. Ahmed, H. Z. Asfour, A. A. Althagafi, H. M. Aldawsari, W. Y. Rizg, W. A. Mahdi, A. F. Alghaith, et al., "Cytotoxic and Pro-Apoptotic Effects of a Sub-Toxic Concentration of Fluvastatin on OVCAR3 Ovarian Cancer Cells After its Optimized Formulation to Melittin Nano-Conjugates.", Frontiers in pharmacology, vol. 11, pp. 642171, 2021. Abstract

Fluvastatin (FLV) is a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor often used to lower total and low-density lipoprotein (LDL) cholesterol and for the prevention of adverse cardiovascular events. This drug as well as melittin (MEL), the major component of honeybee venom (), has shown antineoplastic activity, then representing promising approaches for cancer therapy. However, adverse effects related to the use of FLV and MEL have been reported and very few studies have been carried out to obtain an optimized formulation allowing for combining the two drugs and then maximizing the anticancer activity, then minimizing the needed dosage. In the present study, an optimized formulation in terms of minimized particle size and maximized zeta potential was investigated for its cytotoxic potential in human OVCAR3 ovarian cancer cells. FLV-MEL nano-conjugates, containing a sub-toxic concentration of drug, demonstrated an improved cytotoxic potential (IC50 = 2.5 µM), about 18-fold lower, compared to the free drug (IC50 = 45.7 µM). Cell cycle analysis studies demonstrated the significant inhibition of the OVCAR3 cells proliferation exerted by FLV-MEL nano-conjugates compared to all the other treatments, with a higher percentage of cells accumulating on G2/M and pre-G1 phases, paralleled by lower percentage of cells in G0/G1 and S phases. The synergistic antineoplastic activity of FLV and MEL combined in the optimized formula was also showed by the marked pronecrotic and pro-apoptotic activities, the latter mediated by the modulation of BAX/BCL-2 ratio in favor of BAX. Our optimized FLV-MEL formulation might therefore represents a novel path for the development of specific and more effective antineoplastic drugs directed against ovarian cancer.

Badr-Eldin, S. M., H. M. Aldawsari, O. A. A. Ahmed, N. A. Alhakamy, T. Neamatallah, S. Z. Okbazghi, and U. A. Fahmy, "Optimized semisolid self-nanoemulsifying system based on glyceryl behenate: A potential nanoplatform for enhancing antitumor activity of raloxifene hydrochloride in MCF-7 human breast cancer cells.", International journal of pharmaceutics, vol. 600, pp. 120493, 2021. Abstract

Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator used for treatment and protection against postmenopausal osteoporosis. The drug has been used for protection against breast cancer and more recently, for management of the disease by virtue of its estrogen antagonist action. However, the drug has reduced bioavailability related to low water solubility and first pass metabolism. To surmount these pitfalls, this study aimed at developing and optimizing RLX-loaded semisolid self-nanoemulsifying system (SSNES) with minimized globule size to improve the drug solubility, tumor penetration, and consequently antitumor activity. A simplex lattice mixture design was employed for the formulation and optimization of SSNESs. The mixture components, namely, Compritol® 888 ATO, Tween 20, and polyethylene glycol 200 exhibited significant effect on globule size at P < 0.05. The optimized formulation with globule size of 109.19 ± 2.11 nm showed acceptable thermodynamic stability under stress conditions. Anti-cancer efficacy of the obtained formulation was evaluated in MCF-7 breast cancer cell line. MTT viability assay revealed that RLX-loaded SSNES notably inhibited MCF-7 cell proliferation. Flow cytometry and dual staining with annexin V-FITC/PI were used to assay this anti-proliferative effect and induction of apoptosis, respectively. Cells treated with RLX-loaded SSNES showed significant arrest at G2/M phase associated with significant increase in early/late-stages of apoptotic and necrotic cells. The results exhibited that RLX-loaded SSNES induces apoptosis via the activation of caspase-3 and loss of mitochondrial membrane potential. Accordingly, the proposed SSNES could be regarded as a promising platform for enhancing RLX antitumor activity against breast cancer.

Badr-Eldin, S. M., U. A. Fahmy, H. M. Aldawsari, O. A. A. Ahmed, N. A. Alhakamy, S. Z. Okbazghi, M. A El-Moselhy, A. F. Alghaith, A. Anter, A. I. Matouk, et al., "Optimized Self-Nanoemulsifying Delivery System Based on Plant-Derived Oil Augments Alpha-Lipoic Acid Protective Effects Against Experimentally Induced Gastric Lesions.", Dose-response : a publication of International Hormesis Society, vol. 19, issue 1, pp. 15593258211001259, 2021. Abstract

Peptic ulcer disease is an injury of the alimentary tract that leads to a mucosal defect reaching the submucosa. Alpha-lipoic acid (ALA), a natural potent antioxidant, has been known as a gastroprotective drug yet its low bioavailability may restrict its therapeutic efficacy. This study aimed to formulate and optimize ALA using a self-nanoemulsifying drug delivery system (SNEDDS) with a size of nano-range, enhancing its absorption and augmenting its gastric ulcer protection efficacy. Three SNEDDS components were selected as the design factors: the concentrations of the pumpkin oil (X1, 10-30%), the surfactant tween 80 (X2, 20-50%), and the co-surfactant polyethylene glycol 200 (X3, 30-60%). The experimental design for the proposed mixture produced 16 formulations with varying ALA-SNEDDS formulation component percentages. The optimized ALA-SNEDDS formula was investigated for gastric ulcer protective effects by evaluating the ulcer index and by the determination of gastric mucosa oxidative stress parameters. Results revealed that optimized ALA-SNEDDS achieved significant improvement in gastric ulcer index in comparison with raw ALA. Histopathological findings confirmed the protective effect of the formulated optimized ALASNEDDS in comparison with raw ALA. These findings suggest that formulation of ALA in SNEDDS form would be more effective in gastric ulcer protection compared to pure ALA.

El-Shitany, N. A., S. Harakeh, S. M. Badr-Eldin, A. M. Bagher, B. Eid, H. Almukadi, B. S. Alghamdi, A. A. Alahmadi, N. A. Hassan, N. Sindi, et al., "Minor to Moderate Side Effects of Pfizer-BioNTech COVID-19 Vaccine Among Saudi Residents: A Retrospective Cross-Sectional Study.", International journal of general medicine, vol. 14, pp. 1389-1401, 2021. Abstract

BACKGROUND: The Pfizer-BioNTech COVID-19 vaccine has recently received emergency approval from the US FDA. The mRNA technology was used to manufacture the Pfizer vaccine; however, as a pioneering technology that has never been used in the manufacture of vaccines, many people have concerns about the vaccine's side effects. Thus, the current study aimed to track the short-term side effects of the vaccine.

METHODS: The information in this study was gathered by a Google Form-questionnaire (online survey). The results included the responses of 455 individuals, all of whom are Saudi Arabia inhabitants. Adverse effects of the vaccine were reported after the first and the second doses.

RESULTS: The most common symptoms were injection site pain, headaches, flu-like symptoms, fever, and tiredness. Less common side effects were a fast heartbeat, whole body aches, difficulty breathing, joint pain, chills, and drowsiness. Rare side effects include Bell's palsy and lymph nodes swelling and tenderness. Flu-like symptoms were more common among those under 60 years of age, while injection site pain was more frequent among recipients who were 60 years and older. The study revealed a significant increase in the number of females who suffered from the vaccine side effects compared to males. Difficulty of breathing was more reported among recipients who had been previously infected with the coronavirus compared to those who had not been previously infected.

CONCLUSION: Most of the side effects reported in this study were consistent with Pfizer's fact sheet for recipients and caregivers. Further studies are required to determine the long-term side effects.

Kotta, S., H. M. Aldawsari, S. M. Badr-Eldin, N. A. Alhakamy, and S. Md, "Coconut oil-based resveratrol nanoemulsion: Optimization using response surface methodology, stability assessment and pharmacokinetic evaluation.", Food chemistry, vol. 357, pp. 129721, 2021. Abstract

Phytochemicals are widely studied for therapeutic applications and nanostructured delivery systems for phytochemicals are under spotlight. Resveratrol is a promising candidate for neurodegenerative disorders. In the present study, we aimed to formulate nanoemulsion of resveratrol by ultrasonication process using response surface methodology. The effect of both formulation and ultrasonication process factors were studied for the nanoemulsification process using coconut oil, Pluronic-P107, and Cremophor EL. The time, intensity, and power of ultrasonication were selected as process factors. The globule size, PDI, and zeta potential were the responses selected. The concentrations of oil and surfactant and the intensity were found to significantly influence the globule size. The concentration of resveratrol in the optimized nanoemulsion formulation was 2.6442 mg/ml. The in vitro drug release in pH 6.8 phosphate buffer as well as in vitro permeation study on goat nasal mucosa proved the superiority of the nanoemulsion formulation. On intranasal administration in the rat at a resveratrol dose of 2 mg/kg, the brain targeting efficacy of the nanoemulsion formulation was high. Overall, this research provides the benefit of intake of resveratrol containing fruits and, its incorporation into nanoemulsions system could be a promising alternative for the management of Alzheimer's disease.

Alhakamy, N. A., G. Caruso, M. W. Al-Rabia, S. M. Badr-Eldin, H. M. Aldawsari, H. Z. Asfour, S. Alshehri, S. H. Alzaharani, M. M. Alhamdan, W. Y. Rizg, et al., "Piceatannol-Loaded Bilosome-Stabilized Zein Protein Exhibits Enhanced Cytostatic and Apoptotic Activities in Lung Cancer Cells.", Pharmaceutics, vol. 13, issue 5, 2021. Abstract

Piceatannol (PIC) is a naturally occurring polyphenolic stilbene, and it has pleiotropic pharmacological properties. Moreover, PIC has cytotoxic actions among various cancer cells. In this work, preparations of PIC-loaded bilosome-zein (PIC-BZ) were designed, formulated, and characterized, and the optimized PIC-BZ cytotoxic activities, measured as half maximal inhibitory concentration (IC), against lung cancer cell line was investigated. Box-Behnken design was utilized in order to examine the effect of preparation factors on drug entrapment and particle size. PIC-BZ showed a spherical shape after optimization, and its particle size was determined as 157.45 ± 1.62 nm. Moreover, the efficiency of drug entrapment was found as 93.14 ± 2.15%. The cytotoxic activity evaluation revealed that the adjusted formulation, which is PIC-BZ formula, showed a substantially smaller IC versus A549 cells. Cell cycle analysis showed accumulation of cells in the G2-M phase. Moreover, it showed in the sub-G1 phase, a rise of cell fraction suggestion apoptotic improving activity. Increased early and late phases of apoptosis were demonstrated by staining of cells with annexin V. Furthermore, the cellular caspase-3 protein expression was significantly raised by PIC-BZ. In addition, the wound healing experiment confirmed the results. To conclude, compared to pure PIC, PIC-BZ demonstrated a higher cell death-inducing activity against A549 cells.

Aldawsari, H. M., O. A. A. Ahmed, N. A. Alhakamy, T. Neamatallah, U. A. Fahmy, and S. M. Badr-Eldin, "Lipidic Nano-Sized Emulsomes Potentiates the Cytotoxic and Apoptotic Effects of Raloxifene Hydrochloride in MCF-7 Human Breast Cancer Cells: Factorial Analysis and In Vitro Anti-Tumor Activity Assessment.", Pharmaceutics, vol. 13, issue 6, 2021. Abstract

Raloxifene hydrochloride (RLX), an antiosteoporotic agent, has been utilized for guarding against breast cancer and recently, for the disease management owing to its estrogen antagonist activity. Nevertheless, RLX exhibits poor bioavailability that could be attributed to reduced water solubility and first pass metabolism. To overcome these challenges, this study aimed at formulating and optimizing RLX emulsomes (RLX-EMLs) to enhance the drug antitumor activity. A 43 factorial design was employed for assessing the effect of lipoid: solid lipid ratio and solid lipid type on the emulsomes characteristics. The anticancer potential of the optimized formulation and apoptotic parameters were assessed. Vesicle size, entrapment, and release efficiency were significantly influenced by both variables, while zeta potential was influenced by lipoid: solid lipid at < 0.05. The optimal formulation exhibited vesicle size of 236 ± 8.6 nm, zeta potential of -18.6 ± 0.7 mV, drug entrapment of 98.9 ± 4.9%, and release efficiency of 42.7 ± 1.8%. MTT assay showed concentration-dependent inhibition of MCF-7 cells viability. In addition, cells treated with RLX-EMLs showed significant arrest at G2/M phase associated with significant increase in apoptotic and necrotic cells. The enhanced cytotoxic and anti-proliferative effect of RLX-EMLs relative to raw drug was authenticated through increased Bax/Bcl-2 ratio, caspase-9 activation and depletion of mitochondrial membrane potential.

Alhakamy, N. A., S. M. Badr-Eldin, H. M. Aldawsari, A. Alfarsi, T. Neamatallah, S. Z. Okbazghi, U. A. Fahmy, O. A. A. Ahmad, B. G. Eid, W. A. Mahdi, et al., "Fluvastatin-Loaded Emulsomes Exhibit Improved Cytotoxic and Apoptosis in Prostate Cancer Cells.", AAPS PharmSciTech, vol. 22, issue 5, pp. 177, 2021. Abstract

Fluvastatin (FLV) is known to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), which is over-expressed in various cancers. FLV has been reported to decrease cancer development and metastasis. However, because of low bioavailability, extensive first-pass metabolism and short half-life of FLV (1.2 h), it is not appropriate for clinical application. Therefore, FLV-loaded emulsomes were formulated and optimized using Box-Behnken experimental design to achieve higher efficiency of formulation. Antitumor activity of optimized FLV-loaded emulsomes was evaluated in prostate cancer cells using cell cytotoxicity, apoptotic activity, cell cycle analysis, and enzyme-linked immunosorbent assay. The FLV-loaded emulsomes exhibited a monodispersed size distribution with a mean particle size less than 100 nm as measured by zetasizer. The entrapment efficiency was found to be 93.74% with controlled drug release profile. FLV-EMLs showed a significant inhibitory effect on the viability of PC3 cells when compared to the free FLV (P < 0.0025). Furthermore, FLV-EMLs showed significant arrest in G2/M and increase in percentage of apoptotic cells as compared to free FLV. FLV-EMLs were more effective than free FLV in reducing mitochondrial membrane potential and increase in caspase-3 activity. These results suggesting that FLV-EMLs caused cell cycle arrest which clarifies its significant antiproliferative effect compared to the free drug. Therefore, optimized FLV-EMLs may be an effective carrier for FLV in prostate cancer treatment.