title: Maximizing the Therapeutic Efficacy of Imatinib Mesylate-Loaded Niosomes on Human Colon Adenocarcinoma Using Box-Behnken Design.
abstract: This research purposed to formulate an optimized imatinib mesylate (IM)-loaded niosomes to improve its chemotherapeutic efficacy. The influence of 3 formulation factors on niosomal vesicular size (Y1), zeta potential (Y2), entrapment capacity percentage (Y3), the percentage of initial drug release after 2 h (Y4), and the percentage of cumulative drug release after 24 h (Y5) were studied and optimized using Box-Behnken design. Optimum desirability was specified and the optimized formula was prepared, stability tested, morphologically examined, checked for vesicular bilayer formation and evaluated for its in vitro cytotoxicity on 3 different cancer cell lines namely MCF-7, HCT-116, and HepG-2 in addition to 1 normal cell line to ensure its selectivity against cancer cells. The actual responses of the optimized IM formulation were 425.36 nm, -62.4 mV, 82.96%, 18.93%, and 89.45% for Y1, Y2, Y3, Y4, and Y5, respectively. The optimized IM-loaded niosomes confirmed the spherical vesicular shape imaged by both light and electron microscopes and further proven by differential scanning calorimetry. Moreover, the optimized formula exhibited improved stability on storage at 4 ± 2°C and superior efficacy on MCF7, HCT-116, and HepG2 as IC50values were 6.7, 16.4, and 7.3 folds less than those of free drug, respectively. Interestingly, IC50of the optimized formula against normal cell line was ranged from 3 to 11 folds higher than in different cancer cells indicating a higher selectivity of the optimized formula to cancer cells. In conclusion, the incorporation of IM in niosomes enhanced its efficacy and selectivity toward cancer cells, presenting a promising tool to fight cancer using this approach.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Kassem
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, Egyptian Russian University, Cairo, Egypt.
authors.forename: Hossam S
authors.initials: HS
authors.lastname: El-Sawy
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Fathy I
authors.initials: FI
authors.lastname: Abd-Allah
authors.affiliation: Department of Pharmacology and Toxicology, Al-Azhar University, Cairo, Egypt.
authors.forename: Tamer M
authors.initials: TM
authors.lastname: Abdelghany
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Al-Azhar University, Cairo, Egypt; Department of Pharmaceutics, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: kelsay1@kau.edu.sa.
authors.forename: Khalid M
authors.initials: KM
authors.lastname: El-Say
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage* / Q000494:pharmacology; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; D053769:Nanocapsules; D000068877:Imatinib Mesylate
keywords: cancer cell lines; imatinib mesylate; in vitro cytotoxicity; nanovesicles; optimization