Title : Quality-by-design based development of ibrutinib loaded nanostructured lipid carriers for enhanced bioabsorption
Abstract:
Background: Ibrutinib (IBR) has been accepted as a selective tyrosine kinase inhibitor to be used in the treatment of chronic lymphocytic leukemia (CLL). However, it has low oral bioavailability (2.9 %) which may attributed to low solubility (0.002 mg/ml, BCS class II) and first-pass effect. Ibrutinib-loaded nanostructured lipid carriers (IBR-NLCs) were investigated in this study as a means of increasing bioavailability (BA).
Methods: IBR interaction with solid lipid (GMS) and liquid lipid (oleic acid) was studied using molecular docking. The hot-melt ultrasonication method process was used to formulate the IBR-NLCs, and 32 full factorial design was used for optimization. Particle size, PDI, zeta potential, entrapment efficiency, DSC, XRD, FTIR, and SEM were used to evaluate the NLCs. HepG2 cell lines were used to study IBR-NLCs in vitro cytotoxicity. IBR-NLCs were administered in the presence and absence of cycloheximide (chylomicron blocker) to study pharmacokinetics parameters.
Results: Molecular docking confirmed good interaction between IBR-GMS and IBR-oleic acid. The optimized formulation showed particle size, PDI, zeta potential, and %EE of 153.7 ± 0.75 nm, 0.191 ± 0.003, -26.5 ± 1.10 mV and 84.93 ± 1.20 % respectively. IBR-NLCs exhibited sustained release following Koresmeyer Peppas model. The IC50 values of Blank NLCs and IBR-NLCs were 3.03 and 4.155 µg/ml. The AUC 0-24 of IBR-NLCs administered in the absence of CXI was 1.60 times higher than the AUC 0-24 values in the presence of CXI indicating lymphatic transport.
Conclusion: Thus, the developed IBR-NLCs may be an effective strategy for increasing the oral BA of IBR and avoiding the first-pass effect.
Keynote: Chronic Lymphocytic Leukemia, Nanostructured lipid carriers, Lymphatic targeting
Audience Takes Away Notes:
- Audience will learn that how NLCs can improve the bioavailability, enhancing therapeutic outcomes
- The audience can learn about novel NLCs that can be used for delivery of poorly water-soluble drugs, reducing side effects. By understanding the principles and applications of NLCs, these audiences can contribute to advancements in drug delivery, cosmetics, food technology, and biomedical research, leading to better products and therapies
- In job this knowledge can lead to innovations, improved products, and therapies, making professionals more valuable to their organizations and advancing their careers
- In academics, this presentation will help in designing manufacturing of nanoparticles and its applications and mentor students in research projects involving NLCs
