Acalabrutinib as a novel hope for the treatment of breast and lung cancer: an in-silico proof of concept.

Drug repurposing is proved to be a groundbreaking concept in the field of cancer research, accelerating the pace of de novo drug discovery by investigating the anti-cancer activity of the already approved drugs. On the other hand, it got highly benefitted from the advancement in the in-silico tools and techniques, which are used to build up the initial "proof of concept" based on the drug-target interaction. Acalabrutinib (ACL) is a well-known drug for the treatment of hematological malignancies. But, the therapeutic ability of ACL against solid tumors is still unexplored. Thereby, the activity of ACL on breast cancer and lung cancer was evaluated utilizing different computational methods. A series of proteins such as VEGFR1, ALK, BCL2, CXCR-4, mTOR, AKT, PI3K, HER-2, and Estrogen receptors were selected based on their involvement in the progression of the breast as well as lung cancer. A multi-level computational study starting from protein-ligand docking to molecular dynamic (MD) simulations were performed to detect the binding potential of ACL towards the selected proteins. Results of the study led to the identification of ACL as a ligand that showed a high docking score and binding energy with HER-2, mTOR, and VEGFR-1 successively. Whereas, the MD simulations study has also shown good docked complex stability of ACL with HER2 and VEGFR1. Our findings suggest that interaction with those receptors can lead to preventive action on both breast and lung cancer, thus it can be concluded that ACL could be a potential molecule for the same purpose.Communicated by Ramaswamy H. Sarma.

Amphotericin B loaded nanoemulsion: Optimization, characterization and in-vitro activity against L. donovani promastigotes.

The present work aimed to develop and evaluate AmB-loaded nano-emulsion (AmB-NE) which will augment the solubility of AmB and lead to enhanced anti-leishmanial activity. The composition of AmB-NE was optimized by systematic screening followed by DoE-extreme vertices mixture design. The optimized NE revealed mean droplet size and PDI of 44.19 ± 5.5 nm, 0.265 ± 0.0723, respectively. The NE could efficiently encapsulate AmB with drug content and efficiency 83.509 ± 0.369% and 81.659 ± 0.013%, respectively. The presence of cholesterol and stearyl amine retarded the release (P < 0.0001) of AmB significantly compared to AmB suspension. The AmB-NE and pure AmB suspension demonstrated the IC50 of 0.06309 µg/mL and 0.3309 µg/mL against L.donovani promastigotes after 48 h incubation. The formulation was robust at all exaggerated stability conditions such as freeze-thaw and centrifugation. These findings indicate that AmB-NE is an attractive approach to treat visceral leishmaniasis with improved activity.

Chitosan functionalized PCL nanoparticles bearing tyrosine kinase inhibitor osimertinib mesylate for effective lung cancer therapy.

Lung cancer ranks second position among the cancer-related deaths. Osimertinib mesylate (OSM) is a tyrosine-kinase-inhibitor which can effectively treat non-small cell lung cancer (NSCLC), but still there are certain limitations and side effects which could be circumvented by polymeric nanoparticles approach. Hence, this research was aimed to develop drug-loaded biodegradable polycaprolactone nanoparticles (PCL-NPs) such as OSM-loaded PCL-NPs (PCL-OSM-NPs) and chitosan fabricated OSM-loaded PCL-NPs (CS-PCL-OSM-NPs) to achieve active-targeting of OSM in the cancerous lung tissue. Thus, CS-PCL-OSM-NPs enhance the anticancer efficacy due to active targeting nature and thereby reduces off-target side effects of OSM in the NSCLC treatment. Blank PCL-NPs, PCL-OSM-NPs, and CS-PCL-OSM-NPs were prepared by nanoprecipitation method. Optimized blank PCL-NPs, PCL-OSM-NPs, and CS-PCL-OSM-NPs exhibited the mean particle size of 90.2 ± 4.7 nm, 167.7 ± 2.9 nm, and 233.7 ± 4.8 nm respectively. The encapsulation efficiency % (%EE) of PCL-OSM-NPs was found to be 68.4 ± 3.2%. In vitro drug release study demonstrated sustained release profile of 69.5 ± 5% and 65.7 ± 1.5% for OSM from both the PCL-OSM-NPs and CS-PCL-OSM-NPs, respectively. The PCL-OSM-NPs and CS-PCL-OSM-NPs demonstrated the inhibition of 82.2 ± 0.5% and 81.9 ± 0.2% in A549 cancer cells respectively which clearly signified the improved efficacy. Moreover, the PCL-OSM-NPs and CS-PCL-OSM-NPs exhibited significantly less hemolysis than OSM indicating safety of the formulation. These findings indicate that biohemocompatible CS-PCL-OSM-NPs is an attractive option to treat NSCLC with enhanced anticancer activity and reduced side effects.

Amorphous systems for delivery of nutraceuticals: challenges opportunities.

Amorphous solid products have recently gained a lot of attention as key solutions to improve the solubility and bioavailability of poorly soluble nutraceuticals. A pure amorphous drug is a high-energy form; physically/chemically unstable and so easily gets recrystallized into the less soluble crystalline form limiting solubility and bioavailability issues. Amorphous solid dispersion and co-amorphous are new formulation approach that stabilized unstable amorphous form through different mechanisms such as preventing mobility, high glass transition temperature and molecular interaction. Nutraceuticals have been received the utmost importance due to their health benefits. However, most of these compounds have been associated with poor oral bioavailability due to poor solubility, high lipophilicity, high melting point, poor permeability, degradability and rapid metabolism in the gastrointestinal tract (GIT) which limits its health benefits. This review provides us a systematic application of amorphous systems to the delivery of poorly soluble nutraceuticals, with the aim of overcoming their pharmacokinetic limitations and improved pharmacological potential. In particular, it describes the challenges associated with delivery of oral nutraceuticals, various methods involved in the preparation and characterization of amorphous systems and permeability enhancement of nutraceuticals are in detail.

Budding Multi-matrix Technology-a Retrospective Approach, Deep Insights, and Future Perspectives.

The human race is consistently striving for achieving good health and eliminate disease-causing factors. For the last few decades, scientists have been endeavoring to invent and innovate technologies that can substitute the conventional dosage forms and enable targeted and prolonged drug release at a particular site. The novel multi-matrix technology is a type of matrix formulation where the formulation is embraced to have a matrix system with multiple number of matrices. The MMX technology embraces with a combination of outer hydrophilic layer and amphiphilic/lipophilic core layer, within which drug is encapsulated followed by enteric coating for extended/targeted release at the required site. In comparison to conventional oral drug delivery systems and other drug delivery systems, multi-matrix (MMX) technology formulations afford many advantages. Additionally, it attributes for targeting strategy aimed at the colon and offers modified prolonged drug release. Thus, it has emerged rapidly as a potential alternative option in targeted oral drug delivery. However, the development of this MMX technology formulations is a exigent task and also has its own set of limitations. Due to its promising advantages and colon targeting strategy over the other colon targeted drug delivery systems, premier global companies are exploiting its potential. This article review deep insights into the formulation procedures, drug delivery mechanism, advantages, limitations, safety and efficacy studies of various marketed drug formulations of MMX technology including regulatory perspectives and future perspectives.

Solid self emulsifying drug delivery system: Superior mode for oral delivery of hydrophobic cargos.

A significant proportion of recently approved drug molecules possess poor aqueous solubility which further restrains their desired bioavailability. Poor aqueous solubility of these drugs poses significant hurdles in development of novel drug delivery systems and achieving target response. Self-emulsifying drug delivery systems (SEDDS) emerged as an insightful approach for delivering highly hydrophobic entities to enhance their bioavailability. Conventional SEDDS were developed in a liquid form which owned numerous shortcomings like low stability and drug loading efficiency, fewer choices of dosage forms and irreversible precipitation of drug or excipients. To address these curbs solid-SEDDS (S-SEDDS) was introduced as an efficient strategy that combined advantages of solid dosage forms such as increased stability, portability and patient compliance along with substantial improvement in the bioavailability. S-SEDDS are isotropic mixtures of oil, surfactant, solvent and co-solvents generated by solidification of liquid or semisolid self-emulsifying ingredients onto powders. The present review highlights components of S-SEDDS, their peculiarities to be considered while designing solid dosage forms and various methods of fabrication. Lastly, key challenges faced during development, applications and future directions for the research in this area are thoroughly summarized.

An updated review on exosomes: biosynthesis to clinical applications.

Exosomes are membrane-based extracellular vesicles naturally released by the cells. Nano size range of exosomes and unique properties such as stability, biocompatibility and low immunogenicity are key parameters, which make them suitable as nanoparticulate drug delivery system and also considered as promising delivery carriers for future clinical use. This review outlines the composition, biogenesis, isolation and characterisation methods along with biological and clinical applications of exosomes. Further, the biopharmaceutical features of exosomes include loading method, modified exosomes and potential use of exosomes for different diseases are well explained with the current case studies. We well elaborate the future directions for clinical use of exosomes as drug delivery platforms.