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 (Y), zeta potential (Y), entrapment capacity percentage (Y), the percentage of initial drug release after 2 h (Y), and the percentage of cumulative drug release after 24 h (Y) 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 Y, Y, Y, Y, and Y, 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 IC values were 6.7, 16.4, and 7.3 folds less than those of free drug, respectively. Interestingly, IC of 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.

Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits

“…Development of drug delivery through the traditional procedure is a time, money and energy consuming approach as it based on the changing of one variable at a time while keeping other variables constant. Utilization of the design of experiment (DOE) technique permits investigating large number of factors simultaneously in few experimental runs [ 18 – 23 ].…”

Recent advances in non-ionic surfactant vesicles (niosomes): Fabrication, characterization, pharmaceutical and cosmetic applications

“…It increases the transition temperature of vesicles and hence can improve stability by altering the fluidity of chains in bilayers. When present in sufficient concentration, it abolishes the gel to liquid phase transition endotherm of surfactant bilayers (12,(42)(43)(44)(45)(46).…”

“…Cholesterol also improves EE due to its membrane stabilizing effect, as it distributes between the bilayer, occupying otherwise void space and decreasing membrane fluidity, thus enhancing stability (3,5,(47)(48)(49). On the other hand, increasing cholesterol above a certain point may inhibit the formation of the regular linear structure of the vesicular membrane, as it competes with the drug molecules for space and excludes them (44,50).…”

“…HLB is an empirical expression for the relationship of the hydrophilic and the hydrophobic groups of surfactants (2). Surfactants with a higher HLB value are more water-soluble than surfactants with a lower HLB (8,(42)(43)(44). HLB value affects the size of the niosomes as well as EE of the active ingredient (35,60,61).…”

Nanoformulations to Enhance the Bioavailability and Physiological Functions of Polyphenols

“…With the rapid development of nanotechnology in the food and pharmaceutical industries, many advanced nanoparticles have been developed to protect and control/target the release of biologically active ingredients, including various polyphenols [ 12 , 13 , 14 , 15 ]. The size of nanoparticles and nanocarriers is in the range of 1–100 nm [ 16 ]. By loading phenolic compounds into nanoparticles, not only can their bioavailability be improved, but also the controlled/targeted release and protection of active substances can be achieved [ 17 ].…”