Bahr, M. M., M. Samer, K. Abo-EL-Sooud, S. M. Kamel, M. A. Fouly, A. N. Abdallah, A. A. Shamaa, and O. S. el-Tookhy,
"Effect of Topical application of Lyophilized Xenogenous Mesenchymal Stem Cell-Derived Extracellular Vesicles on Central and Peripheral Corneal Ulcers Healing in Rabbits",
Advances in Animal and Veterinary Sciences, vol. 11, no. 1: ResearchersLinks Ltd, pp. 132 – 140, 2023.
AbstractBackground: Corneal ulcer is the discontinuation of the surface epithelial layer of the cornea with variable amounts of the stroma affected. Recent research suggests that Extracellular Vesicles (EVs) of stem cells have the same effects on target cells that their parental stem cells act, these effects are brought on by paracrine signaling involves the release of cytokines and nucleic acids (DNA, mRNA, and miRNA) which may lead to alteration of the gene expression, proliferation, and differentiation of the recipient cells. Methodology: 24 male New Zealand albino rabbits were used in this study, divided randomly into 4 groups (6 rabbits per group), induction of corneal ulcers centrally in groups (I, II) and peripherally in (III, IV). Treated groups are (I, III) using topical lyophilized canine Mesenchymal Stem Cells derived EVs & control groups are (II, IV) using topical normal saline. Result: both treated groups appeared fluorescein negative at the 5th day and are characterized by rapid reepithelization significantly earlier than control groups which were still fluorescein positive. AS-OCT (Anterior Segment Optical Coherence Tomography) showed well-healed epithelium with intact and homogenous stroma on the 5th day in both treated groups, but control groups showed irregular arrangements of epithelial plaques and presented some abnormalities as stromal fibrosis and sub-epithelial cyst formation. Histopathology in both treated groups showed the development of a complete layer of epithelium within 1week which increased in rows at 2nd and 3rd weeks of treatment and the stromal edema decreased with time unlike control groups that showed weak fragmented epithelium development, sub-epithelial hemorrhage and vascularization. These findings prove that EVs have the ability to heal corneal wounds even if in the peripheral parts of the cornea that are deficient in limbal stem cells. Conclusion: In terms of safety, quality, regulatory concerns, and cost, EVs are superior to corneal transplantation and live stem cell therapy. © 2023 by the authors. Licensee ResearchersLinks Ltd, England, UK. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons. org/licenses/by/4.0/).
Sakr, O. S., M. M. A. Zaitoun, M. Samer, M. Qubisi, A. H. Elshafeey, O. Jordan, and G. Borchard,
"Explosomes: A new modality for DEB-TACE local delivery of sorafenib: In vivo proof of sustained release",
Journal of Controlled Release, vol. 364: Elsevier B.V., pp. 12 – 22, 2023.
AbstractThe current medical practice in treating Hepatocellular carcinoma (HCC) using Drug Eluting Transarterial chemoembolization (DEB-TACE) technique is limited only to hydrophilic ionizable drugs, that can be attached ionically to the oppositely charged beads. This limitation has forced physicians to subscribe the more hydrophobic, first treatment option drugs, like sorafenib systemically via the oral route, thus flooding the patient system with a very powerful, non-specific, multiple-receptor tyrosine kinase inhibitor that is associated with notorious side effects. In this paper, a new modality is introduced, where highly charged, drug loaded liposomes are added to oppositely charged DEBs in a manner causing them to “explode” and the drug is eventually attached to the beads in the lipid patches covering their surfaces; therefore we call them “Explosomes”. After fully describing the preparation process and in vitro characterization, this manuscript delves into an in vivo pharmacokinetic study over 50 New Zealand rabbits, where explosomal loading is challenged vs oral as well as current practice of emulsifying sorafenib in lipiodol. Over 14 days of follow up, and compared to other groups, explosomal loading of SRF on embolic beads proved to cause a slower release pattern with longer Tmax, lower Cmax and less washout to general circulation in healthy animals. This treatment modality opens a new untapped door for local sustained delivery of hydrophobic drugs in catheterized organs. © 2023 Elsevier B.V.