Harnessing the nutriceutics in early-stage breast cancer: mechanisms, combinational therapy, and drug delivery.

BACKGROUND: Breast cancer (BC) is a significant health challenge, ranking as the second leading cause of cancer-related death and the primary cause of mortality among women aged 45 to 55. Early detection is crucial for optimal prognosis. Among various treatment options available for cancer, chemotherapy remains the predominant approach. However, its patient-friendliness is hindered by cytotoxicity, adverse effects, multi-drug resistance, potential for recurrence, and high costs. This review explores extensively studied phytomolecules, elucidating their molecular mechanisms. It also emphasizes the importance of combination therapy, highlighting recent advancements in the exploration of diverse drug delivery systems and novel routes of administration. The regulatory considerations are crucial in translating these approaches into clinical practices. RESULTS: Consequently, there is growing interest in exploring the relationship between diet, cancer, and complementary and alternative medicine (CAM) in cancer chemotherapy. Phytochemicals like berberine, curcumin, quercetin, lycopene, sulforaphane, resveratrol, epigallocatechin gallate, apigenin, genistein, thymoquinone have emerged as promising candidates due to their pleiotropic actions on target cells through multiple mechanisms with minimal toxicity effects. This review focuses on extensively studied phytomolecules, elucidating their molecular mechanisms. It also emphasizes the importance of combination therapy, highlighting recent advancements in the exploration of diverse drug delivery systems and novel routes of administration. The regulatory considerations are crucial in translating these approaches into clinical practices. CONCLUSION: The present review provides a comprehensive understanding of the molecular mechanisms, coupled with well-designed clinical trials and adherence to regulatory guidelines, which pave the way for nutrition-based combination therapies to become a frontline approach in early-stage BC treatment.

Nano revolution of DNA nanostructures redefining cancer therapeutics-A comprehensive review.

DNA nanostructures are a promising tool in cancer treatment, offering an innovative way to improve the effectiveness of therapies. These nanostructures can be made solely from DNA or combined with other materials to overcome the limitations of traditional single-drug treatments. There is growing interest in developing nanosystems capable of delivering multiple drugs simultaneously, addressing challenges such as drug resistance. Engineered DNA nanostructures are designed to precisely deliver different drugs to specific locations, enhancing therapeutic effects. By attaching targeting molecules, these nanostructures can recognize and bind to cancer cells, increasing treatment precision. This approach offers tailored solutions for targeted drug delivery, enabling the delivery of multiple drugs in a coordinated manner. This review explores the advancements and applications of DNA nanostructures in cancer treatment, with a focus on targeted drug delivery and multi-drug therapy. It discusses the benefits and current limitations of nanoscale formulations in cancer therapy, categorizing DNA nanostructures into pure forms and hybrid versions optimized for drug delivery. Furthermore, the review examines ongoing research efforts and translational possibilities, along with challenges in clinical integration. By highlighting the advancements in DNA nanostructures, this review aims to underscore their potential in improving cancer treatment outcomes.

Exosome-Based Macromolecular neurotherapeutic drug delivery approaches in overcoming the Blood-Brain barrier for treating brain disorders.

Delivering drugs to the brain is a complex challenge in medical research, particularly for disorders like Alzheimer's and Parkinson's. The blood-brain barrier restricts the entry of many therapeutic molecules, hindering their effectiveness. Nanoparticles, a potential solution, face issues like toxicity and limited approvals. A new avenue explores the use of small extracellular vesicles (sEVs), i.e., exosomes, as natural carriers for drug delivery. sEVs, tiny structures below 150 nm, show promise due to their minimal immune response and ability to precisely deliver drugs. This review focuses on the potential of sEVs-based drug delivery systems for treating neurological disorders, brain cancers, and other brain-related issues. Notably, bioengineered sEVs-carrying therapeutic compounds exhibit promise in early studies. The unique features of sEVs, such as their small size and natural properties, position them as candidates to overcome challenges in drug delivery to the brain. Ongoing clinical trials and research into sEVs behavior within the body further highlight their potential for revolutionizing drug delivery and addressing complex brain conditions.

Simultaneous quantification of 4-hydroxytamoxifen and hesperidin in liposomal formulations: Development and validation of a RP-HPLC method.

Breast cancer treatment options are diverse, with tamoxifen commonly used as a selective estrogen receptor modulator (SERM) for hormone receptor-positive breast cancer. However, tamoxifen can have adverse systemic effects. Local transdermal therapy offers a potential solution by delivering the drug directly to the breast and minimizing systemic exposure. Hesperidin, a flavonoid, exerts synergistic effects when combined with anticancer agents. This combination therapy may be a more effective approach to breast cancer management. Analytical methods have been developed to quantify 4-Hydroxytamoxifen (4-HT) and hesperidin separately; however, no method currently exists for their simultaneous quantification in pharmaceutical formulations. This study aimed to develop and validate a reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous quantification of 4-HT and hesperidin in liposomal formulations. A Design of Experiments (DoE) approach was employed using a Box-Behnken design (BBD) to optimize the RP-HPLC method. BBD allowed for a reduction in the number of required tests by creating a statistical model to estimate the significance of various factors and interactions. The methanol concentration, flow rate, and injection volume were considered as independent variables for optimization. A mobile phase (90:10 ratio of methanol: 0.1% v/v orthophosphoric acid) with a flow rate of 0.4 mL/min, and an injection volume of 10 µL was selected as optimized chromatographic condition. 4-HT showed a retention time (Rt) of 5.05 min and hesperidin showed an Rt of 7.11 min using an optimized analytical method and was detected at 275 nm. The developed RP-HPLC method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, confirming its accuracy, precision, linearity, selectivity, and robustness. The validated method was then successfully applied to determine the entrapment efficiency and permeation of 4-HT and hesperidin into loaded liposomes. This study fills a gap in the literature by providing a simple and reliable RP-HPLC method for the simultaneous quantification of 4-HT and hesperidin in liposomal formulations.

Non-systemic Approaches for Ductal Carcinoma In Situ: Exploring the Potential of Ultra-flexible Combisomes as a Novel Drug Delivery Strategy-a Review.

Ductal carcinoma in situ (DCIS) is currently treated through breast-conserving surgery (lumpectomy), radiation therapy, breast-removing surgery (mastectomy), and hormone therapy to prevent further progression into invasive breast cancer and recurrence. Discrepancies concerning the prognosis of DCIS have sparked controversy about adequate treatment. Considering the severe medical and psychological consequences of mastectomy, developing a treatment approach that arrests the progression of DCIS to the invasive stage without affecting the non-cancerous cells is of utmost importance. In the current review, the problems associated with the diagnosis and management of DCIS have been thoroughly discussed. A summary of the route of administration and drug delivery systems to manage DCIS was also provoked. Innovative ultra-flexible combisomes were also proposed for the effective management of DCIS. Prevention is essential in managing the risk of DCIS and reducing the risk of progression to invasive breast cancer. While prevention is vital, it is not always possible to prevent DCIS, and in some cases, treatment may be necessary. Hence, this review recommends that ultra-flexible combisomes administered as a topical gel provide a non-systemic approach for managing DCIS and thus significantly minimize the side effects and costs associated with existing therapies.

A Review on Exploring Better Safety Prospects in Managing Cancer using Liposomal Combinations of Food Bioactive Compounds and Anticancer Drugs: Combisomes.

Nowadays, cancer is one of the deadliest diseases affecting an annually enormous number of people. Around 9.6 million people had died from different cancer types in 2018. Chemotherapy is considered to be a mainline treatment, and systemic administration of a single anticancer agent is also considered a vital clinical debacle of chemotherapy in cancer management. The formulators have been focusing currently onto procuring maximum benefit with the lowest aftereffects and maximum safety and efficacy for the patients undergoing chemotherapy. This review offers a perspective on the future developments of encapsulating food bioactive compounds with anticancer agents in a multifunctional single nanoliposomal delivery system. In the last decade, the paradigm shift was seen in formulating drug delivery systems for cancer treatment. Currently, food bioactive compounds are being taken as a hot subject by researchers, especially for the treatment of cancer owing to both preventative and curative quality. This review collects the utilization of liposomes in the delivery of anticancer drugs by encapsulating with food bioactive compounds by the oral administration. The authors coined the name of this combination is "Combisomes" as a fourth generation liposomes. Authors opine that "Combisomes" can tackle cancer minimizing side effects encountered from the usual anticancer agents. "Combisomes" will purvey a safe platform for the delivery of food bioactive compounds and anticancer agents for managing cancer with better safety prospects.

Development and characterization of a cell line WAF from freshwater shark Wallago attu.

A new epithelial cell line, WAF was developed from caudal fin of freshwater shark, Wallago attu. The cell line was optimally maintained at 28 °C in Leibovitz-15 (L-15) medium supplemented with 20 % fetal bovine serum. The cell line was characterized by various cytogenetic and molecular markers. The cytogenetic analysis revealed a diploid count of 86 chromosomes at different passages. The origin of the cell lines was confirmed by the amplification of 547 and 654 bp sequences of 16S rRNA and cytochrome oxidase subunit I genes of mitochondrial DNA, respectively. WAF cells were characterized for their growth characteristics at different temperature and serum concentration. Epithelial morphology of the cell line was confirmed using immunocytochemistry. Further cell plating efficiency, transfection efficiency and viability of cryopreserved WAF cells was also determined. Cytotoxicity and genotoxicity assessment of cadmium salts on WAF cells by MTT, NR and comet assay illustrated the utility of this cell line as an in vitro model for aquatic toxicological studies. The cell line will be further useful for studying oxidative stress markers against aquatic pollutants.

Acute electrocardiographic changes during smoking: an observational study.

OBJECTIVE: To study the temporal relationship of smoking with electrophysiological changes. DESIGN: Prospective observational study. SETTING: Tertiary cardiac center. PARTICIPANTS: Male smokers with atypical chest pain were screened with a treadmill exercise test (TMT). A total of 31 such patients aged 49.8±10.5 years, in whom TMT was either negative or mildly positive were included. Heart rate variability (HRV) parameters of smokers were compared to those of 15 healthy non-smoking participants. INTERVENTIONS: All patients underwent a 24 h Holter monitoring to assess ECG changes during smoking periods. RESULTS: Heart rate increased acutely during smoking. Mean heart rate increased from 83.8±13.7 bpm 10 min before smoking, to 90.5±16.4 bpm during smoking, (p<0.0001) and returned to baseline after 30 min. Smoking was also associated with increased ectopic beats (mean of 5.3/h prior to smoking to 9.8/h during smoking to 11.3/h during the hour after smoking; p<0.001). Three patients (9.7%) had significant ST-T changes after smoking. HRV index significantly decreased in smokers (15.2±5.3) as compared to non-smoking controls participants (19.4±3.6; p=0.02), but the other spectral HRV parameters were comparable. CONCLUSIONS: Heart rate and ectopic beats increase acutely following smoking. Ischaemic ST-T changes were also detected during smoking. Spectral parameters of HRV analysis of smokers remained in normal limits, but more importantly geometrical parameter-HRV index-showed significant abnormality.

Study on antioxidant activity of common dry fruits.

This study investigates the antioxidant activity of different dry fruits (almonds, walnut, cashew nut, raisins, chironji) through several chemical and biochemical assays: reducing power, lipid peroxidation damage in biomembranes, determination of antioxidant enzymes activity (SOD and CAT). To estimate the total phenolic content, the assay using Folin-Ciocalteu reagent was used. The EC(50) values were calculated for all the methods in order to evaluate the antioxidant efficiency of each dry fruit. The results obtained were quite heterogenous, revealing significant differences among the dry fruits. The methanolic extract of walnut showed the higher value of antioxidant activity based on lipid peroxidation assay. The higher phenolic content was found in walnuts followed by almonds cashew nut, chironji and least phenolic content was found in raisins. Walnut revealed the best antioxidant properties, presenting lower EC(50) values in all assays except in antioxidant enzymatic activity.