Publications by authors named "Hamad Alrbyawi"

4 Publications

  • Page 1 of 1

Co-Delivery of Hispolon and Doxorubicin Liposomes Improves Efficacy Against Melanoma Cells.

AAPS PharmSciTech 2020 Nov 4;21(8):304. Epub 2020 Nov 4.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, 36849, USA.

Hispolon is a small molecular weight polyphenol that has antioxidant, anti-inflammatory, and anti-proliferative activities. Our recent study has demonstrated hispolon as a potent apoptosis inducer in melanoma cell lines. Doxorubicin is a broad spectrum first-line treatment for various kinds of cancers. In this study, co-delivery of doxorubicin and hispolon using a liposomal system in B16BL6 melanoma cell lines for synergistic cytotoxic effects was investigated. Liposomes were prepared using a lipid film hydration method and loaded with doxorubicin or hispolon. The formulations were characterized for particle size distribution, release profile, and encapsulation efficiency (EE). In addition, in vitro cytotoxicity, in vitro cell apoptosis, and cellular uptake were evaluated. Liposomes exhibited small particle size (mean diameter ~ 100 nm) and narrow size distribution (polydispersity index (< 0.2) and high drug EE% (> 90%). The release from liposomes showed slower release compared to free drug solution as an additional time required for the release of drug from the liposome lipid bilayer. Liposome loaded with doxorubicin or hispolon exhibited significantly higher cytotoxicity against B16BL6 melanoma cells as compared to doxorubicin solution or hispolon solution. Likewise, co-delivery of hispolon and doxorubicin liposomes showed two-fold and three-fold higher cytotoxicity, as compared to hispolon liposomes or doxorubicin liposomes, respectively. In addition, co-delivery of doxorubicin and hispolon in liposomes enhanced apoptosis more than the individual drugs in the liposome formulation. In conclusion, the co-delivery of hispolon and doxorubicin could be a promising therapeutic approach to improve clinical outcomes against melanoma.
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http://dx.doi.org/10.1208/s12249-020-01846-2DOI Listing
November 2020

Elucidating the anti-melanoma effect and mechanisms of Hispolon.

Life Sci 2020 Sep 6;256:117702. Epub 2020 May 6.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, AL 36849. Electronic address:

There is a rapid increase in the incidence of melanoma which has led to a global crisis. Thus, there is a great need for developing novel, safe and effective drugs for the treatment of melanoma. Hispolon is a small molecular weight polyphenol derived from Phellinus linteus, which has antioxidant, anti-inflammatory and anti-proliferative activities. Hispolon has been reported to induce apoptosis in gastric cancer, hepatocellular carcinoma, and myeloid leukemia. However, the anticancer effect in melanoma is not well elucidated. Thus, our present study was to investigate the anti-cancer effect of hispolon on melanoma cancer cells. B16BL6 cells were treated with different concentrations of hispolon for 24 h and the effect on oxidative stress, mitochondrial functions, apoptosis and cell proliferation were studied. Hispolon is a potent generator of reactive oxygen species, nitrite and lipid peroxide levels. Furthermore, it significantly inhibits the expression of Bcl-2 and promotes the expression of Bax, increases the activity of caspase 1 and 3, inhibits mitochondrial Complex I and IV activities. By the above mechanisms, hispolon dose-dependently exhibited the antimelanoma effect similar to the well established pharmacological agent, curcumin. Thus, hispolon can be a potent anti-melanoma drug in the future if the pharmacodynamic effects and the toxicological studies are appropriately carried out.
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http://dx.doi.org/10.1016/j.lfs.2020.117702DOI Listing
September 2020

Role of Ceramides in Drug Delivery.

AAPS PharmSciTech 2019 Aug 13;20(7):287. Epub 2019 Aug 13.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, 36849, USA.

Ceramides belong to the sphingolipid group of lipids, which serve as both intracellular and intercellular messengers and as regulatory molecules that play essential roles in signal transduction, inflammation, angiogenesis, and metabolic disorders such as diabetes, neurodegenerative diseases, and cancer cell degeneration. Ceramides also play an important structural role in cell membranes by increasing their rigidity, creating micro-domains (rafts and caveolae), and altering membrane permeability; all these events are involved in the cell signaling. Ceramides constitute approximately half of the lipid composition in the human skin contributing to barrier function as well as epidermal signaling as they affect both proliferation and apoptosis of keratinocytes. Incorporation of ceramides in topical preparations as functional lipids appears to alter skin barrier functions. Ceramides also appear to enhance the bioavailability of drugs by acting as lipid delivery systems. They appear to regulate the ocular inflammation signaling, and external ceramides have shown relief in the anterior and posterior eye disorders. Ceramides play a structural role in liposome formulations and enhance the cellular uptake of amphiphilic drugs, such as chemotherapies. This review presents an overview of the various biological functions of ceramides, and their utility in topical, oral, ocular, and chemotherapeutic drug delivery.
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http://dx.doi.org/10.1208/s12249-019-1497-6DOI Listing
August 2019

Co-delivery of Doxorubicin and Ceramide in a Liposomal Formulation Enhances Cytotoxicity in Murine B16BL6 Melanoma Cell Lines.

AAPS PharmSciTech 2019 Feb 4;20(3):99. Epub 2019 Feb 4.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, 36849, USA.

This study reports co-delivery of doxorubicin (DOX) and ceramide in a liposomal system in B16BL6 melanoma cell lines for enhanced cytotoxic effects. Different types of ceramides (C6-ceramide, C8-ceramide, and C8-glucosylceramide) and lipids (1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)) were considered in the preparation of liposomes. DOX was encapsulated within liposome, and ceramide was used as the component of the lipid bilayer. The formulations were optimized for size and size distribution, zeta potential, and DOX encapsulation efficiency (EE). Cytotoxic effect on B16BL6 melanoma cell lines was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The ceramide based liposome formulations generally provided a mean diameter < 181 nm, a zeta potential, + 35 mV, and EE > 90% DOX EE. Co-delivery of DOX and C8-ceramide with DOTAP liposomes demonstrated significantly higher cytotoxicity as compared to DOX liposomes without ceramide (P < 0.001), and also showed enhanced cellular uptake by B16BL6 cell lines. This study provides basis for developing a co-delivery system of DOX and ceramide for lowering the dose and dose-related side effects of DOX for the treatment of melanoma.
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http://dx.doi.org/10.1208/s12249-019-1316-0DOI Listing
February 2019