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.

Polymersomes Based Versatile Nanoplatforms for Controlled Drug Delivery and Imaging.

Drug delivery systems made based on nanotechnology represent a novel drug carrier system that can change the face of therapeutics and diagnosis. Among all the available nanoforms polymersomes have wider applications due to their unique characteristic features like drug loading carriers for both hydrophilic and hydrophobic drugs, excellent biocompatibility, biodegradability, longer shelf life in the bloodstream and ease of surface modification by ligands. Polymersomes are defined as the artificial vesicles which are enclosed in a central aqueous cavity which are composed of self-assembly with a block of amphiphilic copolymer. Various techniques like film rehydration, direct hydration, nanoprecipitation, double emulsion technique and microfluidic technique are mostly used in formulating polymersomes employing different polymers like PEO-b-PLA, poly (fumaric/sebacic acid), poly(N-isopropylacrylamide) (PNIPAM), poly (dimethylsiloxane) (PDMS), and poly(butadiene) (PBD), PTMC-b-PGA (poly (dimethyl aminoethyl methacrylate)-b-poly(l-glutamic acid)) etc. Polymersomes have been extensively considered for the conveyance of therapeutic agents for diagnosis, targeting, treatment of cancer, diabetes etc. This review focuses on a comprehensive description of polymersomes with suitable case studies under the following headings: chemical structure, polymers used in the formulation, formulation methods, characterization methods and their application in the therapeutic, and medicinal filed.

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.

Self-nanoemulsifying drug delivery systems (SNEDDS) of anti-cancer drugs: a multifaceted nanoplatform for the enhancement of oral bioavailability.

OBJECTIVE: A significant problem faced by the health care industry today is that though there are numerous drugs available to tackle diseases like cancer, their intrinsic properties make it difficult to be delivered to patients in a feasible manner. One of the key players that have helped researchers overcome poor solubility and permeability of drugs is Nanotechnology, this article further iterates on the same. SIGNIFICANCE: Nanotechnology is used as an umbrella term in pharmaceutics and describes under it multiple technologies. Upcoming nanotechnology is a Self Nanoemulsifying System which is considered to be a futuristic delivery system both due to its scientific simplicity and relative ease of patient delivery. METHODS: Self-Nano Emulsifying Drug Delivery Systems (SNEDDS) are homogenous lipidic concoctions containing the drug solubilized in the oil phase and surfactants. The choice of components depends on the physicochemical properties of the drugs, the solubilization capability of oils and the physiological fate of the drug. The article contains further details of various methodologies that have been adopted by scientists to formulate and optimize such systems in order to make anticancer drugs orally deliverable. RESULTS: The results that have been generated by scientists across the globe have been summarized in the article and all of the data supports the claim that SNEDDS significantly enhance the solubility and bioavailability of hydrophobic anticancer drugs. CONCLUSIONS: This article mainly provides the application of SNEDDS in cancer therapy and concludes to provide a step for the oral administration of several BCS class II and IV anticancer drugs.