An Innovative Formulation Based on Nanostructured Lipid Carriers for Imatinib Delivery: Pre-Formulation, Cellular Uptake and Cytotoxicity Studies.

Imatinib (IMT) is a tyrosine kinase enzyme inhibitor and extensively used for the treatment of gastrointestinal stromal tumors (GISTs). A nanostructured lipid carrier system (NLCS) containing IMT was developed by using emulsification-sonication methods. The characterization of the developed formulation was performed in terms of its particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, loading capacity, sterility, syringeability, stability, in vitro release kinetics with mathematical models, cellular uptake studies with flow cytometry, fluorescence microscopy and cytotoxicity for CRL-1739 cells. The particle size, PDI, loading capacity and zeta potential of selected NLCS (F16-IMT) were found to be 96.63 ± 1.87 nm, 0.27 ± 0.15, 96.49 ± 1.46% and -32.7 ± 2.48 mV, respectively. F16-IMT was found to be stable, thermodynamic, sterile and syringeable through an 18 gauze needle. The formulation revealed a Korsmeyer-Peppas drug release model of 53% at 8 h, above 90% of cell viability, 23.61 µM of IC50 and induction of apoptosis in CRL-1739 cell lines. In the future, F16-IMT can be employed to treat GISTs. A small amount of IMT loaded into the NLCSs will be better than IMT alone for therapy for GISTs. Consequently, F16-IMT could prove to be useful for effective GIST treatment.

The effect of radiolabeled nanostructured lipid carrier systems containing imatinib mesylate on NIH-3T3 and CRL-1739 cells.

The aim of current study is to develop new nanostructured lipid carrier systems (NLCSs) containing imatinib mesylate (IMT) and evaluate their targeting efficiency on NIH-3T3 as fibroblast cells and CRL-1739 as gastric adenocarcinoma cells with radiolabeled formulations. Three formulations (F1-IMT, F2-IMT and F3-IMT) were prepared and radiolabeled with 1 mCi/0.1 mL of [99mTc]Tc. The effect of reducing and antioxidant agents on radiolabeling process was evaluated and radiochemical purity of formulations was performed by radio thin-layer radiochromatography (RTLC). The results demonstrated that the radiochemical purity was found to be above 90% for [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT, while radiochemical purity of [99mTc]Tc-F3-IMT was found to be 85.61 ± 2.24%. Also, [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT have better stability in cell medium and saline than [99mTc]Tc-F3-IMT. Targeting efficiency of [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT comparatively evaluated by cell binding studies with [99mTc]NaTcO4 on NIH-3T3 and CRL-1739 cells. The cell binding capacity and targeting/non-targeting cell uptake ratio of these two formulations was found to be higher than [99mTc]NaTcO4 in CRL-1739. It is thought that the knowledge achieved in this study would contribute to using [99mTc]Tc-F1-IMT and [99mTc]Tc F2-IMT as an diagnosis and treatment agents.

Applying Quality by Design Principles in the Development and Preparation of a New Radiopharmaceutical: Technetium-99m-Imatinib Mesylate.

The clinical impact and accessibility of 99mTc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. In this study, Technetium-99m-imatinib mesylate ([99mTc]TcIMT) was developed and prepared as a new radiopharmaceutical for breast cancer diagnosis. The effect of critical process parameters on the product quality and stability of [99mTc]TcIMT was investigated using the quality by design concept of the ICH Q8 (Pharmaceutical Development) guideline. [99mTc]TcIMT was subjected to in vitro cell binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. The optimal radiolabeling procedure with 1 mg of IMT, 500 µg of stannous chloride, 0.1 mg of ascorbic acid, and 1mCi 99mTc radioactivity was obtained for [99mTc]TcIMT. The pH of the reaction mixture was adjusted to 10 and allowed to react for 15 min at room temperature. The radiochemical purity of [99mTc]TcIMT was found to be higher than 90% at room temperature up to 6 h. Chromatography analysis revealed >85% [99mTc]TcIMT complex formation with promising stability in saline, cell medium, and serum up to 6 h. The radiolabeled complex showed a higher cell-binding ratio to MCF-7 cells (88.90% ± 3.12) than HaCaT cells (45.64 ± 4.72) when compared to 99mTc. Our findings show that the developed preparation method for [99mTc]TcIMT falls well within the proven acceptable ranges. Applying quality by design (QbD) principles is feasible and worthwhile for the preparation of [99mTc]TcIMT. In conclusion, radiochemical purity, stability, and in vitro cell binding evaluation of the [99mTc]TcIMT complex indicate that the agent can be utilized for imaging of breast cancer cells.