Recent Advances in the Treatment Strategies of Friedreich's Ataxia: A Review of Potential Drug Candidates and their Underlying Mechanisms.

BACKGROUND: Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism. OBJECTIVE: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action. METHODS: A comprehensive literature search was conducted using various authentic scientific databases to identify studies published in the last decade that investigated potential treatment strategies for FRDA. The search terms used included "Friedreich's ataxia," "treatment," "drug candidates," and "mechanisms of action." RESULTS: To date, only one drug got approval from US-FDA in the year 2023; however, significant developments were achieved in FRDA-related research focusing on diverse therapeutic interventions that could potentially alleviate the symptoms of this disease. Several promising drug candidates have been identified for the treatment of FRDA, which target various aspects of frataxin deficiency and aim to restore frataxin levels, reduce oxidative stress, and improve mitochondrial function. Clinical trials have shown varying degrees of success, with some drugs demonstrating significant improvements in neurological function and quality of life in FRDA patients. CONCLUSION: While there has been significant progress in the development of treatment strategies for FRDA, further research is needed to optimize these approaches and identify the most effective and safe treatment options for patients. The integration of multiple therapeutic strategies may be necessary to achieve the best outcomes in FRDA management.

Development of erlotinib-loaded nanotransferosomal gel for the topical treatment of ductal carcinoma in situ.

Aims: This study was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma in situ. Materials & methods: The optimized process involved a thin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generate ERL@TG. The optimized formulation was characterized in vitro followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed in vivo. Results: In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC50 values with an enhanced safety profile. Conclusion: Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma in situ breast cancer.

Despite progress, breast cancer remains a significant cause of death. This study aimed to revolutionize the treatment of noninvasive ductal carcinoma in situ, a type of breast cancer, by developing a special gel that can be applied directly to the breast. The developed gel was in the nanoform, a 'nanotransfersomal' gel that contained erlotinib, a potent drug for breast cancer. To ensure its effectiveness, we evaluated the erlotinib-loaded transfersomal gel through various tests. The results confirmed that the gel was nano-sized and loaded with a high amount of erlotinib. Animal studies were conducted to check if the prepared gel caused any skin irritation and interestingly, there was no irritation observed on the animals' skin. Furthermore, we treated breast cancer cells with the developed gel using a method called MTT assay and the results showed improved cell-killing activity in comparison to plain drug. In conclusion, this special gel represents a breakthrough in breast cancer treatment. It offers hope for better outcomes in the fight against this disease. This innovative approach involves directly applying the gel on the affected area topically to increase patient compliance and decreasing side effects of drugs. This could potentially transform ductal carcinoma in situ breast cancer treatment, bringing us closer to improved treatments and outcomes.

Multivariate Statistical 2D QSAR Analysis of Indenoisoquinoline-based Topoisomerase- I Inhibitors as Anti-lung Cancer Agents.

BACKGROUND: Indenoisoquinoline-based compounds have shown promise as topoisomerase-I inhibitors, presenting an attractive avenue for rational anticancer drug design. However, a detailed QSAR study on these derivatives has not been performed till date. OBJECTIVE: This study aimed to identify crucial molecular features and structural requirements for potent topoisomerase- 1 inhibition. METHODS: A comprehensive two-dimensional (2D) QSAR analysis was performed on a series of 49 indenoisoquinoline derivatives using TSAR3.3 software. A robust QSAR model based on a training set of 33 compounds was developed achieving favorable statistical values: r2 = 0.790, r2CV = 0.722, f = 36.461, and s = 0.461. Validation was conducted using a test set of nine compounds, confirming the predictive capability of the model (r2 = 0.624). Additionally, artificial neural network (ANN) analysis was employed to further validate the significance of the derived descriptors. RESULTS: The optimized QSAR model revealed the importance of specific descriptors, including molecular volume, Verloop B2, and Weiner topological index, providing essential insights into effective topoisomerase-1 inhibition. We also obtained a robust partial least-square (PLS) analysis model with high predictive ability (r2 = 0.788, r2CV = 0.743). The ANN results further reinforced the significance of the derived descriptors, with strong r2 values for both the training set (r2 = 0.798) and the test set (r2 = 0.669). CONCLUSION: The present 2D QSAR analysis offered valuable molecular insights into indenoisoquinoline-based topoisomerase- I inhibitors, supporting their potential as anti-lung cancer agents. These findings contribute to the rational design of more effective derivatives, advancing the development of targeted therapies for lung cancer treatment.

Amelioration of the therapeutic potential of gefitinib against breast cancer using nanostructured lipid carriers.

Aim: This study aimed to improve the delivery and therapeutic potential of gefitinib (GTB) against breast cancer by preparing GTB-loaded, nanostructured lipid carriers (GTB-NLCs). Materials & methods: Box-Behnken design was used for optimization and GTB was loaded into NLCs using ultrasonication. The GTB-NLCs were characterized using in vitro, ex vivo and in vivo studies. The anticancer efficacy of GTB-NLCs was evaluated using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity and flow cytometry on MCF-7 breast cancer cell lines. Results: Optimized GTB-NLCs were successfully characterized and demonstrated improved internalization and enhanced cytotoxicity compared with plain GTB. Gut permeation studies showed enhanced intestinal permeability, and pharmacokinetic analysis revealed 2.6-fold improvement in GTB oral bioavailability. Conclusion: GTB-NLCs effectively enhanced the therapeutic potential of GTB against breast cancer.

Gefitinib is an important drug approved for the treatment of cancer. However, there are issues with gefitinib, including its low water solubility and toxicity. Being poorly water soluble, the absorption of gefitinib in blood is low and therefore high doses are required to achieve the therapeutic level. Also, gefitinib is nonselective for cancer as well as noncancer cells, leading to toxicity on other organs. This study aimed to incorporate gefitinib into a lipid-based carrier, which improved its properties such as solubility, stability and bioavailability. The prepared formulation was tested for its drug release, stability and efficacy on breast cancer cell lines as well as toxicity using various methods. It was observed that the prepared formulation not only improved bioavailability but also improved the targeting as more gefitinib entered the cancer cells when present in the formulation, decreasing the toxicity of gefitinib on other organs. In conclusion, the prepared formulation can be regarded as an effective approach to improving the therapeutic potential of gefitinib.

Bromelain: a review of its mechanisms, pharmacological effects and potential applications.

The utilization of plant-derived supplements for disease prevention and treatment has long been recognized because of their remarkable potential. Ananas comosus, commonly known as pineapple, produces a group of enzymes called bromelain, which contains sulfhydryl moieties. Recent studies have shown that bromelain exhibits a wide range of activities, including anti-inflammatory, anti-diabetic, anti-cancer, and anti-rheumatic properties. These properties make bromelain a promising drug candidate for the treatment of various diseases. The anti-inflammatory activity of bromelain has been shown to be useful in treating inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and asthma, whereas the anti-cancer activity of bromelain is via induction of apoptosis, inhibition of angiogenesis, and enhancement of the body's immune response. The anti-diabetic property of bromelain is owing to the improvement in glucose metabolism and reduction in insulin resistance. The therapeutic potential of bromelain has been investigated in numerous preclinical and clinical studies and a number of patents have been granted to date. Various formulations and delivery systems are being developed in order to improve the efficacy and safety of this molecule, including the microencapsulated form to treat oral inflammatory conditions and liposomal formulations to treat cancer. The development of novel drug delivery systems and formulations has further ameliorated the therapeutic potential of bromelain by improving its bioavailability and stability, while reducing the side effects. This review intends to discuss various properties and therapeutic applications of bromelain, along with its possible mechanism of action in treating various diseases. Recent patents and clinical trials concerning bromelain have also been covered.

A review of nanomaterials from synthetic and natural molecules for prospective breast cancer nanotherapy.

Breast cancer being one of the most frequent cancers in women accounts for almost a quarter of all cancer cases. Early and late-stage breast cancer outcomes have improved dramatically, with considerable gains in overall survival rate and disease-free state. However, the current therapy of breast cancer suffers from drug resistance leading to relapse and recurrence of the disease. Also, the currently used synthetic and natural agents have bioavailability issues which limit their use. Recently, nanocarriers-assisted delivery of synthetic and natural anticancer drugs has been introduced to the breast cancer therapy which alienates the limitations associated with the current therapy to a great extent. Significant progress has lately been made in the realm of nanotechnology, which proved to be vital in the fight against drug resistance. Nanotechnology has been successfully applied in the effective and improved therapy of different forms of breast cancer including invasive, non-invasive as well as triple negative breast cancer (TNBC), etc. This review presents a comprehensive overview of various nanoformulations prepared for the improved delivery of synthetic and natural anticancer drugs alone or in combination showing better efficacy and pharmacokinetics. In addition to this, various ongoing and completed clinical studies and patents granted on nanotechnology-based breast cancer drug delivery are also reviewed.

Superparamagnetic Iron-Oxide Nanoparticles Synthesized via Green Chemistry for the Potential Treatment of Breast Cancer.

In the emerging field of nanomedicine, nanoparticles have been widely considered as drug carriers and are now used in various clinically approved products. Therefore, in this study, we synthesized superparamagnetic iron-oxide nanoparticles (SPIONs) via green chemistry, and the SPIONs were further coated with tamoxifen-conjugated bovine serum albumin (BSA-SPIONs-TMX). The BSA-SPIONs-TMX were within the nanometric hydrodynamic size (117 ± 4 nm), with a small poly dispersity index (0.28 ± 0.02) and zeta potential of -30.2 ± 0.09 mV. FTIR, DSC, X-RD, and elemental analysis confirmed that BSA-SPIONs-TMX were successfully prepared. The saturation magnetization (Ms) of BSA-SPIONs-TMX was found to be ~8.31 emu/g, indicating that BSA-SPIONs-TMX possess superparamagnetic properties for theragnostic applications. In addition, BSA-SPIONs-TMX were efficiently internalized into breast cancer cell lines (MCF-7 and T47D) and were effective in reducing cell proliferation of breast cancer cells, with IC50 values of 4.97 ± 0.42 µM and 6.29 ± 0.21 µM in MCF-7 and T47D cells, respectively. Furthermore, an acute toxicity study on rats confirmed that these BSA-SPIONs-TMX are safe for use in drug delivery systems. In conclusion, green synthesized superparamagnetic iron-oxide nanoparticles have the potential to be used as drug delivery carriers and may also have diagnostic applications.

Gefitinib: An Updated Review of its Role in the Cancer Management, its Nanotechnological Interventions, Recent Patents and Clinical Trials.

BACKGROUND: Gefitinib, a tyrosine kinase inhibitor, is effectively used in the targeted treatment of malignant conditions. It suppresses the signal transduction cascades leading to cell proliferation in the tumors and is now currently approved in several countries globally as secondline and third-line treatment for non-small cell lung cancer (NSCLC). OBJECTIVE: This review is aimed to summarize the journey of gefitinib as an established anticancer drug for the management of various cancers. Moreover, this review will focus on the mechanism of action, established anticancer activities, combination therapy, nanoformulations, as well as recent clinical trials and patents on gefitinib. METHODS: The data for this review was collected from scientific databases such as PubMed, Science Direct, Google Scholar, etc. Recent patents on gefitinib granted in the last two years were collected from databases Patentscope, USPTO, Espacenet, InPASS and Google Patents. Data for the recent clinical trials were obtained from the U.S. National Library of Medicine database. RESULTS: Recent pre-clinical and clinical studies during the period 2015-2021 demonstrating the efficacy of gefitinib were selected and summarized. Total 31 patents were granted in the year 2020-2021 concerning gefitinib. The efficacy of gefitinib against lung cancer, as well as other cancer types, including breast, prostate, colon, cervix etc., was reviewed. CONCLUSION: Gefitinib showed significant advantages in being more effective, safer and more stable, and the associated biopharmaceutical problems are addressed by the application of nanotechnology. The combination therapy using gefitinib and various anticancer molecules of natural and synthetic origin has shown an improved anticancer profile.

Design-of-Experiments (DoE)-Assisted Fabrication of Quercetin-Loaded Nanoemulgel and Its Evaluation against Human Skin Cancer Cell Lines.

Background: Quercetin (QCT) is a natural polyphenolic flavonoid showing great potential in the treatment of skin cancer. However, its use is limited owing to its poor water solubility, poor absorption, quick metabolism and excretion, as well as low stability. Preparation of nanoemulgel has been proven to be an effective approach to deliver the drugs topically due to various advantages associated with it. Objectives: This study aimed to prepare stable nanoemulgel of QCT using a Design-of-Experiments (DoE) tool for optimization, to characterize and to assess its in vivo toxicity and efficacy against human cancer cell lines in vitro. Methods: An ultrasonication emulsification method was used for the preparation of QCT-loaded nanoemulsion (QCT@NE). Box-Behnken design was used for the optimization of developed nanoemulgel. Then, in vitro characterization of prepared nanoemulsion was performed using Fourier Transform-Infra Red (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM), particle size analysis, determination of zeta potential and entrapment efficiency (%EE). Further, the developed QCT-loaded nanoemulgel (QCT@NG) was characterized in vitro using texture profile analysis, viscosity and pH determination. Eventually, the cell cytotoxicity studies of the prepared nanoemulgel were performed on the skin cancer cell lines A431 followed by an acute toxicity and skin irritation study on male wistar rats in vivo. Results: The developed QCT@NE was found to be nanometric in size (173.1 ± 1.2 nm) with low polydispersity index (0.353 ± 0.13), zeta potential (-36.1 ± 5.9 mV), and showed good %EE (90.26%). The QCT@NG was found to be substantially more effective against the human skin carcinoma (A431) cell lines as compared to plain QCT with IC50 values of 108.5 and 579.0 µM, respectively. Skin irritation study showed no sign of toxicity and ensured safety for topical application. Hematological analysis revealed no significant differences between the treatment and control group in any biochemical parameter. In the nanoemulgel treatment group, there were no discernible differences in the liver enzymes, bilirubin, hemoglobin, total leukocyte and platelet counts as compared to the control group. Conclusions: The optimized QCT@NG was found to be an ideal and promising formulation for the treatment of skin cancer without showing skin irritation and organ toxicity.

From propolis to nanopropolis: An exemplary journey and a paradigm shift of a resinous substance produced by bees.

Propolis, a natural resinous mixture produced by honey bees is poised with diverse biological activities. Owing to the presence of flavonoids, phenolic acids, terpenes, and sesquiterpenes, propolis has garnered versatile applications in pharmaceutical industry. The biopharmaceutical issues associated with propolis often beset its use as being too hydrophobic in nature; it is not absorbed in the body well. To combat the problem, various nanotechnological approaches for the development of novel drug delivery systems are generally applied to improve its bioavailability. This paradigm shift and transition of conventional propolis to nanopropolis are evident from the literature wherein a multitude of studies are available on nanopropolis with improved bioavailability profile. These approaches include preparation of gold nanoparticles, silver nanoparticles, magnetic nanoparticles, liposomes, liquid crystalline formulations, solid lipid nanoparticles, mesoporous silica nanoparticles, etc. Nanopropolis has further been explored to assess the potential benefits of propolis for the development of futuristic useful products such as sunscreens, creams, mouthwashes, toothpastes, and nutritional supplements with improved solubility, bioavailability, and penetration profiles. However, more high-quality clinical studies assessing the effects of propolis either alone or in combination with synthetic drugs as well as natural products are warranted and its safety needs to be firmly established.

Quercetin loaded silver nanoparticles in hydrogel matrices for diabetic wound healing.

Quercetin (QCT) is an effective antioxidant, antifibrotic and wound healing agent. Silver nanoparticles (AgNPs) are an effective antimicrobial, antifungal and wound healing agent and considered as gold standard for wound treatment especially diabetic and burn wounds. The present study aimed to investigate QCT loaded AgNPs in hydrogel matrices (QCT-AgNPs hydrogel) as synergistic treatment paradigms for diabetic wound. Quality by Design approach was employed for the optimization of hydrogel preparation using carbopol-934 andaloevera.The developed QCT-AgNPs hydrogel was characterized for hydrodynamic diameter, %entrapment efficiency (%EE), surface morphology, texture analysis,in-vitrodrug release, skin irritation study,ex-vivopermeation study (confocal study), and antimicrobial efficacy. The optimized formulation showed hydrodynamic diameter of ∼44.1 nm with smooth spherical surface morphology and ∼92.09% of QCT was entrapped in QCT-AgNPs hydrogel matrices. The antimicrobial study revealed superior therapeutic efficacy of QCT-AgNPs hydrogel in comparison to marketed (MRKT) gel onS. aureusandE. coli. Moreover,in-vivoresults demonstrated that QCT-AgNPs hydrogel significantly (p < 0.001) reduced the wound gap and increased % re-epithelialization compared with diabetic control after 18 d of post treatment in excisional diabetic wound model. In conclusion, this study opens up an avenue for the treatment of diabetic wound.

Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials.

Traditionally, herbal supplements have shown an exceptional potential of desirability for the prevention of diseases and their treatment. Sulforaphane (SFN), an organosulfur compound belongs to the isothiocyanate (ITC) group and is mainly found naturally in cruciferous vegetables. Several studies have now revealed that SFN possesses broad spectrum of activities and has shown extraordinary potential as antioxidant, antitumor, anti-angiogenic, and anti-inflammatory agent. In addition, SFN is proven to be less toxic, non-oxidizable, and its administration to individuals is well tolerated, making it an effective natural dietary supplement for clinical trials. SFN has shown its ability to be a promising future drug molecule for the management of various diseases mainly due to its potent antioxidant properties. In recent times, several newer drug delivery systems were designed and developed for this potential molecule in order to enhance its bioavailability, stability, and to reduce its side effects. This review focuses to cover numerous data supporting the wide range of pharmacological activities of SFN, its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials on SFN are also summarized.

Nanocarriers-Assisted Needle-Free Vaccine Delivery Through Oral and Intranasal Transmucosal Routes: A Novel Therapeutic Conduit.

Drug delivery using oral route is the most popular, convenient, safest and least expensive approach. It includes oral transmucosal delivery of bioactive compounds as the mucosal cavity offers an intriguing approach for systemic drug distribution. Owing to the dense vascular architecture and high blood flow, oral mucosal layers are easily permeable and can be an ideal site for drug administration. Recently, the transmucosal route is being investigated for other therapeutic candidates such as vaccines for their efficient delivery. Vaccines have the potential to trigger immune reactions and can act as both prophylactic and therapeutic conduit to a variety of diseases. Administration of vaccines using transmucosal route offers multiple advantages, the most important one being the needle-free (non-invasive) delivery. Development of needle-free devices are the most recent and pioneering breakthrough in the delivery of drugs and vaccines, enabling patients to avoid needles, reducing anxiety, pain and fear as well as improving compliance. Oral, nasal and aerosol vaccination is a novel immunization approach that utilizes a nanocarrier to administer the vaccine. Nanocarriers improve the bioavailability and serve as adjuvants to elicit a stronger immune response, resulting in increased effectiveness of vaccination. Drugs and vaccines with lower penetration abilities can also be delivered transmucosally while maintaining their biological function. The development of micro/nanocarriers for transmucosal delivery of macromolecules, vaccines and other substances is currently drawing much attention and a number of studies were performed recently. This comprehensive review is aimed to summarize the most recent investigations on needle-free and non-invasive approaches for the delivery of vaccines using oral transmucosal route, their strengths and associated challenges. The oral transmucosal vaccine delivery by nanocarriers is the most upcoming advancement in efficient vaccine delivery and this review would help further research and trials in this field.

Lipid-nanopotentiated combinatorial delivery of tamoxifen and sulforaphane: ex vivo, in vivo and toxicity studies.

Aim: This study aims to load tamoxifen (TAM) and sulforaphane (SFN) into nanostructured lipid carriers (NLCs) to enhance their oral delivery. Materials & methods: TAM-SFN-NLCs were prepared using Precirol® ATO5 and Transcutol® HP, characterized and evaluated in vitro and ex vivo to assess the drug release profile and intestinal permeability, respectively. In vivo pharmacokinetic and acute toxicity assessment was performed in Wistar rats. Results: Optimized TAM-SFN-NLCs exhibited a particle size of 121.9 ± 6.42 nm and zeta potential of -21.2 ± 2.91 mV. The NLCs enhanced intestinal permeability of TAM and SFN and augmented oral bioavailability of TAM and SFN 5.2-fold and 4.8-fold, respectively. SFN significantly reduced TAM-associated toxicity in vivo. Conclusion: This coencapsulation of a chemotherapeutic agent with a herbal bioactive in NLCs could pave a novel treatment approach against cancer.

Reassessment of Therapeutic Applications of Carbon Nanotubes: A Majestic and Futuristic Drug Carrier.

Carbon nanotubes (CNTs) have been identified as one of the most advanced and versatile nanovectors, theranostics, and futuristic drug delivery tools for highly effective delivery of genes, drugs, and biomolecules, as well as for use in bioimaging and as biosensors. CNTs have drawn tremendous attention and interest from researchers worldwide in the past two decades owing to a number of unique characteristics including well defined physicochemical properties, large surface area, in addition to exclusive electrical and optical properties. Numerous recent literature related to the design and applications of CNTs were studied and summarized accordingly. Special emphasis was given for the applications of CNTs in drug targeting. Specific targeting of anticancer drugs such as cisplatin, doxorubicin, taxol, gemcitabine, and methotrexate, and delivery of small interfering RNA, micro-RNA, as well as plasmid DNA have been successfully assisted using CNTs. All the major applications of CNTs were summarized in detail with possible toxicity concerns associated with them. As far as their toxicity is concerned, it was noticed that the functionalized CNTs pose little toxicity and do not have immunogenic effects. In conclusion, CNTs showed great potential in developing a new generation of carriers for various drugs and related biomolecules. The application of CNTs ranges from physics to chemistry and now they are expanding their roles in the therapeutic drug delivery in the modern healthcare system. With applications in every imaginable route of administration, CNTs bring therapeutic benefits to society. The pharmaceutical, biopharmaceutical, pharmacokinetic, pharmacodynamic, and clinical efficacy of CNTs is explored in detail in this review.

Nanostructured lipid carrier potentiated oral delivery of raloxifene for breast cancer treatment.

Nanotherapeutics in cancer treatment are dominating global science and research, and have been recognized as the pioneering medical care regimen. Raloxifene (RLN) has been used for its anti-proliferative action on mammary tissue, however, it suffers from poor oral bioavailability. This investigation gives an account of the design and development of RLN-loaded nanostructured lipid carriers (RLN-NLCs) using a simple and scalable ultrasonication method for improved oral efficacy and limited offsite toxicity using Compritol® 888 ATO as a solid lipid and Transcutol® HP as a liquid lipid. In addition, the optimized RLN-NLCs were in the nanometric range (121 nm) with high % entrapment efficiency (%EE) (81%) for RLN, and were further freeze-dried in the presence of mannitol to enhance the stability of RLN-NLCs in the dry state for long-term use. Morphological observation under a transmission electron microscope and scanning electron microscope revealed the spherical smooth surface nanometric size of RLN-NLCs. Powder x-ray diffraction confirmed the encapsulation of RLN into the RLN-NLC's matrix with reduced crystallinity of the drug. The in vitro release study showed a burst release for an initial 4 h, and sustained release for up to 24 h. Furthermore, the RLN-NLCs showed higher cytotoxicity towards MCF-7 cells in vitro in comparison to RLN suspension, and an ex vivo intestinal permeation study demonstrated improved intestinal permeability of RLN-NLCs. Moreover, the in vivo pharmacokinetic study in female Wistar rats showed a 4.79-fold increment in oral bioavailability of RLN from RLN-NLCs compared to RLN suspension. Taken together, our results pave the way for a new nanotherapeutic approach towards breast cancer treatment.

Recent Advancements in the Diagnosis, Prevention, and Prospective Drug Therapy of COVID-19.

Severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2), previously called 2019 novel CoV, emerged from China in late December 2019. This virus causes CoV disease-19 (COVID-19), which has been proven a global pandemic leading to a major outbreak. As of June 19, 2020, the data from the World Health Organization (WHO) showed more than 8.7 million confirmed cases in over 200 countries/regions. The WHO has declared COVID-19 as the sixth public health emergency of international concern on January 30, 2020. CoVs cause illnesses that range in severity from the common cold to severe respiratory illnesses and death. Nevertheless, with technological advances and imperative lessons gained from prior outbreaks, humankind is better outfitted to deal with the latest emerging group of CoVs. Studies on the development of in vitro diagnostic tests, vaccines, and drug re-purposing are being carried out in this field. Currently, no approved treatment is available for SARS-CoV-2 given the lack of evidence. The results from preliminary clinical trials have been mixed as far as improvement in the clinical condition and reduction in the duration of treatment are concerned. A number of new clinical trials are currently in progress to test the efficacy and safety of various approved drugs. This review focuses on recent advancements in the field of development of diagnostic tests, vaccines, and treatment approaches for COVID-19.

PEGylated Nanoliposomes Potentiated Oral Combination Therapy for Effective Cancer Treatment.

The conventional treatment regimen for cancer with a single chemotherapeutic agent is far behind the clinical expectations due to the complexity of cancer biology and is also associated with poor Quality of Life (QOL) due to off-site toxicity and multidrug resistance. In recent years, nanopotentiated combination therapy has shown significant improvement in cancer treatment via a synergistic approach. However, being synthetic in nature, nanocarriers have been associated with the activation of the Complement (C) activation system resulting in serious hypersensitivity reactions known as CActivation Related Pseudoallergy (CARPA) effect once given via intravenous injection. On the other hand, nanopotentiated oral drug delivery offers several advantages for the effective and safe delivery of the drug to the target site. This hypothesis aims to put forward wherein Exemestane (chemotherapeutic agent) and lycopene (herbal bioactive) co-laden into PEGylated liposomes and delivered to the breast cancer via the oral route. PEGylation of the liposomes would prevent both molecules from the harsh microenvironment of the Gastrointestinal Tract (GIT) and would eventually promote their intestinal absorption via the lymphatic pathway to the systemic circulation. Lycopene being a potent antioxidant and anti-cancer herbal bioactive would promote the therapeutic efficacy of the Exemestane via a synergistic approach. This nanopotentiated oral combination therapy would pave the path for the safe and effective treatment of cancer.

Development and validation of a high throughput bioanalytical UPLC-MS/MS method for simultaneous determination of tamoxifen and sulphoraphane in rat plasma: Application to an oral pharmacokinetic study.

Tamoxifen (TAM) is the choice of a drug approved by the Food and Drug Administration (FDA) for the treatment of estrogen-positive receptor (ER+) breast cancer. Sulphoraphane (SFN), a natural plant antioxidant compound, also acts on estrogen-positive breast cancer receptor. Thus, a combination of TAM with SFN is preferred as it helps to minimize the drug-related toxicity and increases the therapeutic efficacy by providing synergistic anticancer effects of both drugs. In the present study, a new simple, sensitive, precise, and selective UPLC-MS/MS method was developed for the simultaneous quantification of tamoxifen and sulphoraphane using propranolol as an internal standard (IS) in rat plasma. Chromatographic separation was achieved on reverse phase Acquity UPLC BEH C18 column (50 mm × 2.1 mm, i.d., 1.7 µm) with an isocratic mobile phase composed of solvent A (0.1% formic acid in acetonitrile) and B (0.1% formic acid in water) (80:20, v/v) at a flow-rate of 0.4 mL/min. The detection and quantification of analytes was performed on Waters ZsprayTM Xevo TQD using selected-ion monitoring operated under a positive electrospray ionization mode. The transitions were m/z = 372.0 [M+H]+ → 71.92 for tamoxifen, m/z = 177.9 [M+H]+ → 113.9 for sulphoraphane and m/z = 260.3 [M+H]+ → 116.1 for propranolol. The method was linear over the concentration range of 8-500 ng/mL (r2 = 0.9996) for tamoxifen, 30-2000 ng/mL (r2 = 0.9998) for sulphoraphane with insignificant matrix effect and high extraction recovery on spiked quality control (QC) samples. The intra- and inter-batch precisions and accuracy were within the acceptable limits, and both the analytes were found to be stable throughout the short term, long term and freeze thaw stability studies. The validated method was successfully applied for the simultaneous estimation of TAM and SFN in an oral pharmacokinetic study in female Wistar rats. This developed UPLC-MS/MS method could be a valuable tool for future pharmacokinetic interaction, therapeutic drug monitoring and pharmacokinetic characterization of novel formulations.

Tamoxifen and Sulphoraphane for the breast cancer management: A synergistic nanomedicine approach.

Breast cancer is second most leading cause of death in all over the world and not only limited to the females. Tamoxifen has been considered as the gold line therapy for estrogen receptor positive breast cancer. However, this chemopreventive approach has been focused at individuals in high risk group and limits its clinical applications to moderate and/or lower risk groups. Moreover, Tamoxifen treatment is associated with a dose related hepatotoxicity and nephrotoxicity and eventually results in poor quality of life of patients. Sulphoraphane, a naturally occurring isothiocyanate derivative has been investigated for its numerous potential biological activities including anticancer effects. The present hypothesis aims to put forward in which Tamoxifen is combined with a natural bioactive Sulphoraphane, both incorporated into a novel lipid based nanocarrier at a reduced dose, which would eventually shuttle the cargo to the target site. At the breast cancer, Sulphoraphane sensitizes the estrogen receptors and ameliorates the binding affinity of Tamoxifen to these receptors, thereby potentiating the anticancer efficacy and reducing the offsite toxicity of Tamoxifen. This dual loaded zero-dimension lipid carrier would be a value addition to the current treatment regimen for breast cancer management.