In Silico Screening as a Tool to Prepare Drug-Drug Cocrystals of Ibrutinib-Ketoconazole: a Strategy to Enhance Their Solubility Profiles and Oral Bioavailability.

Ibrutinib (IBR) is a biopharmaceutical classification system (BCS) class II drug and an irreversible Bruton's tyrosine kinase (BTK) inhibitor. IBR has an extremely low oral bioavailability due to the activity of the CYP3A4 enzyme. The current intention of the research was to enhance solubility followed by oral bioavailability of IBR using the hot melt extrusion (HME) technique by formulating drug-drug cocrystals (DDCs). Ketoconazole (KET) is an active CYP3A4 inhibitor and was selected based on computational studies and solubility parameter prediction. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM) evaluations were employed for estimating the formation of IBR-KET DDCs. The IBR-KET DDC system was discovered to have a hydrogen bond (H-bond) and π-π-stacking interactions, in accordance with the computational results. Further, IBR-KET DDCs showed enhanced solubility, stability, powder dissolution, in vitro release, and flow properties. Furthermore, IBR-KET-DDCs were associated with enhanced cytotoxic activity in K562-CCL-243 cancer cell lines when compared with IBR and KET alone. In vivo pharmacokinetic studies have shown an enhanced oral bioavailability of up to 4.30 folds of IBR and 2.31 folds of KET through IBR-KET-DDCs compared to that of the IBR and KET suspension alone. Thus, the prepared IBR-KET-DDCs using the HME technique stand as a favorable drug delivery system that augments the solubility and oral bioavailability of IBR along with KET.

Highlights on Cell-Penetrating Peptides and Polymer-Lipid Hybrid Nanoparticle: Overview and Therapeutic Applications for Targeted Anticancer Therapy.

Polymer-lipid hybrid nanoparticles (PLHNs) have been widely used as a vehicle for carrying anticancer owing to its unique framework of polymer and lipid combining and giving the maximum advantages over the lipid and polymer nanoparticle drug delivery system. Surface modification of PLHNs aids in improved targeting and active delivery of the encapsulated drug. Therefore, surface modification of the PLHNs with the cell-penetrating peptide is explored by many researchers and is explained in this review. Cell-penetrating peptides (CPPs) are made up of few amino acid sequence and act by disrupting the cell membrane and transferring the cargos into the cell. Ideally, we can say that CPPs are peptide chains which are cell specific and are biocompatible, noninvasive type of delivery vehicle which can transport siRNA, protein, peptides, macromolecules, pDNA, etc. into the cell effectively. Therefore, this review focuses on the structure, type, and method of preparation of PLHNs also about the uptake mechanism of CPPs and concludes with the therapeutic application of PLHNs surface modified with the CPPs and their theranostics.