Incorporation of exemestane into ternary nanosponge system for enhanced anti-tumor potential in breast cancer.

The present investigation reports the potential of exemestane loaded cyclodextrin based nanosponges for the treatment of breast cancer. Fourier transform infrared, and nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the encapsulation of ring B, C, and D of exemestane in the nanosponge cavity. In vitro studies demonstrated a 6.58-folds increase in the aqueous solubility and a 1.76-folds increase in the dissolution of exemestane in the optimized nanosponge formulation EF2. It also exhibited enhanced cytotoxicity in MCF-7 cell line. Pharmacokinetic studies revealed a 1.37-fold increase in Cmax and a 2.10-fold increase in oral bioavailability of EF2, as compared to its marketed product Aromasin®. Concomitantly, this nano-formulation reduced the tumor burden to 45.71% in a DMBA-induced breast cancer rat model. This EF2-treatment also improved the hematological parameters of the animals. Histopathology of breast tissue also presented reduction in characteristic cytoarchitectural features of breast tumor. In vivo toxicity studies demonstrated reduced hepatotoxicity of the nanosponge formulation when compared with Aromasin®. These results were further supported by histological studies of excised liver tissues, where the size of hepatocytes in EF2-treated animals was like the normal hepatocyte size. In conclusion, the encapsulation of exemestane in ß-cyclodextrin nanosponge along-with HPMC E5 improved its aqueous solubility, bioavailability, and ultimately therapeutic efficacy for the treatment of breast cancer.

High-resolution liquid chromatography and mass spectrometry (HR-LCMS) assisted phytochemical profiling and an assessment of anticancer activities of Gracilaria foliifera and Turbinaria conoides using in vitro and molecular docking analysis.

Marine algae's, owing to diverse range of secondary metabolites, opening up the new avenues in new drug development and can be used efficiently in anticancer research. Two seaweeds Gracilaria foliifera and Turbinaria conoides are subjected to phytochemical investigation by HR-LCMS and NMR which confirms presence of different bioactive compounds. The cytotoxicity of the dichloromethane (DCM) fraction of Gracilaria foliifera and Turbinaria conoides was determined using an in vitro methyl thiazolyl tetrazolium (MTT) test and showed considerable dose-dependent cytotoxicity on tumour cell lines. In MCF7, Gracilaria foliifera had an IC50 of 100 µg/ml, while Turbinaria conoides had an IC50 of 200 µg/ml and both the DCM fraction had IC50 values of 100 µg/ml in the A549 cell line. MTT assay for anticancer activity suggest that Gracilaria foliifera has potent anticancer activity in both breast and lung cell lines, while the DCM fraction of Turbinaria conoides has potent activity in lung cell lines and moderate activity in breast cell lines. The anticancer effects of the discovered drugs targeting the most prevalent enzymes VEGFR and AXL tyrosine kinases were confirmed using a computational technique. We believe that residues from VEGFR, like Lys868, Asn923, Asp1046, and Phe1047 and Asp690 from Axl kinase may have contributed to the plausible anti-cancer benefit seen in this study.Communicated by Ramaswamy H. Sarma.

Cyclodextrin Based Nanosponges: A Multidimensional Drug Delivery System and its Biomedical Applications.

Cyclodextrin based nanosponges are the designed nanocarriers for the projected delivery of complex drugs. They are multifunctional hypercrosslinked cyclodextrin polymers connected in a three-dimensional, mesh-like network. Their functional characteristics can be fabricated by using different crosslinkers or their different rations with polymer. They can encapsulate various hydrophilic, lipophilic, small-sized or large-sized drug molecules. They offer formulation flexibility and are primarily used for solubility, bioavailability and stability enhancement purposes. This system is also pliable for co-delivery of pharmaceutical entities, improving therapeutic efficacy and patient compliance. If the surface of nanosponge is coupled with an appropriate ligand, even a target specific drug delivery can be achieved. It has a variety of applications in the field of pharmacy for the delivery of tricky drug molecules, proteins, enzymes, natural moieties and gaseous compounds. The list of its applications further widens with the development of nanodiagnostics, nanosensors, biomimetics and scaffolds based on nanosponges. The sudden explosion of research in this working area signifies cyclodextrin nanosponge based products in the market soon.