Background: Estrogens are essential for the growth of breast cancer in case of premenopausal as well as in postmenopausal women. However, most of the breast cancer incidences are reported in postmenopausal women and the concurrent risk surges with increase in age. Since the enzyme aromatase, catalyses essential steps in estrogen biosynthesis, Aromatase Inhibitors (AIs) are effective targeted therapy in patients with Estrogen Receptor positive (ER+ ) breast cancer. AIs are more effective than Selective Estrogen Receptor Modulators (SERMs) because they block both the genomic and nongenomic activities of ER. Till date, first, second and third generation AIs have been approved by FDA. The third generation AIs, viz. Letrozole, Anastrozole, Exemestane, are currently used in the standard treatment for postmenopausal breast cancer.AIs are more effective than Selective Estrogen Receptor Modulators (SERMs) because they block both the genomic and nongenomic activities of ER. Till date, first, second and third generation AIs have been approved by FDA. The third generation AIs, viz. Letrozole, Anastrozole, Exemestane, are currently used in the standard treatment for postmenopausal breast cancer. Methods: Data were collected from Medline, PubMed, Google Scholar, Science Direct through searching of keywords: ‘aromatase’, ‘aromatase inhibitors’, ‘breast cancer’, ‘steroidal aromatase inhibitors’, ‘non-steroidal inhibitors’ and ‘generations of aromatase inhibitors’. Results: In current scenario of breast cancer chemotherapy, AIs are the most widely used agents which revealing optimum efficacy along with least side effects. Keeping in view the prominence of AIs in breast cancer therapy, this review covered the detailed description of aromatase including its, role in biosynthesis of estrogen, biochemistry, gene expression, 3Dstructure, and information of reported AIs along with their role in breast cancer treatment. Results: In current scenario of breast cancer chemotherapy, AIs are the most widely used agents which revealing optimum efficacy along with least side effects. Keeping in view the prominence of AIs in breast cancer therapy, this review covered the detailed description of aromatase including its, role in biosynthesis of estrogen, biochemistry, gene expression, 3Dstructure, and information of reported AIs along with their role in breast cancer treatment. Conclusion: AIs are the mainstream solution of ER+ breast cancer treatment regimen with the continuous improvement of human understanding of the importance of healthy life of women suffering from breast cancer.

Background: It takes lot more studies to evaluate the molecular interaction of nanoparticles with the drug, their drug delivery potential and release kinetics. Thus, we have taken in silico and in vitro approaches into the account for the evaluation of drug delivery ability of the chitosan nanoparticles. Objective: The present work was aimed to develop the interaction of chitosan nanoparticles with appropriate aromatase inhibitors using in-silico tools. Further, synthesis and characterization of chitosan nanoparticles having optimal binding energy and affinity between drug and polymer in terms of size, encapsulation efficiency was carried out. Methods: In current study, molecular docking was used to map the molecular interactions and estimation of binding energy involved between the nanoparticles and the drug molecules in silico. Letrozole is used as a model cytotoxic agent currently being used clinically, hence Letrozole loaded chitosan nanoparticles were formulated and characterized using photomicroscope, particle size analyzer, scanning electron microscope and fourier transform infra-red spectroscopy. Results: Letrozole had the second highest binding affinity within the core of chitosan with MolDock (-102.470) and Rerank (-81.084) scores. Further, it was investigated that formulated nanoparticles were having superior drug loading capacity and high encapsulation efficiency. In vitro drug release study exhibited prolonged release of the drug from chitosan nanoparticles. Conclusion: Results obtained from the in silico and in vitro studies suggest that Letrozole loaded nanoparticles are ideal for breast cancer treatment.

Mitochondria play a pivotal role in cardioprotection. The major cardioprotective mechanism is ischemic preconditioning (IpreC), through which short periods of ischemia protect a subsequent prolonged acute ischemic episode. Mitochondria channels, particularly the potassium channels (mitoK) such as ATP-dependent and calcium-activated potassium channels, have been suggested as trigger or end effectors in IpreC. Activators of mitoK are promising therapeutic agents for the treatment of the myocardial injury due to ischemic episodes. In this chapter, we are summarizing our current knowledge on the physiology function of different mitochondrial channels with a focus on the potassium channels and their mechanism in cardioprotection. Furthermore, the currently under development therapy by targeting the mitochondrial channels for the treatment of heart failure are also discussed.

Background: β-Cyclodextrin, a cyclic oligosaccharides having 7 macrocyclic ring of glucose sub units usually linked together by ɑ-1,4 glycosidic bond, bears characteristic chemical structure, with exterior portion as hydrophilic to impart water solubility and interior cavity as hydrophobic, for hosting the hydrophobic molecules. Objective: In the present work binding affinities and interactions between various anti-cancerous drugs and β-cyclodextrin using molecular docking simulations was examined for the bioavailability enhancement of cytotoxic drugs through improved solubility for the treatment of breast cancer. Methods: Molegro Virtual Docker, an integrated software was used for the prediction and estimation of interaction between βcyclodextrin and anti cancerous drugs. Results: Out of tested anti cancerous drug, Olaparib having pyridopyridazione scaffold possess highest MolDock (-130.045) and Reranks score (-100.717), ensuring strong binding affinity. However, 5-Fluoro Uracil exhibited lowest MolDock score (-61.0045), indicating weak or no binding affinity, while few drugs showed no H-bond interaction with the β-cyclodextrin. Conclusion: The binding conformations of anti cancerous drugs obtained from the present study can be selected for development of improved formulation having superior solubility which will lead to attain better pharmacological profile with negligible toxicity.

Background: The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS1000) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. Materials & methods: A quality-by-design approach was applied for optimization and in vitro and in vivo characterization were performed. Results: The TPP-TPGS1000-PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and G2M cell cycle arrest compared with free-PTX treatment. In addition, pharmacokinetics, biodistribution and  in vivo live imaging studies in tumor-bearing mice showed that TPP-TPGS1000-PTX-NE had superior performance compared with free-PTX treatment. Histological and survival investigations ascertained the nontoxicity of the nanoformulation, suggesting new opportunities and potential to treat breast cancer. Conclusion: TPP-TPGS1000-PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity.