Advancements in targeting tumor suppressor genes (p53 and BRCA 1/2) in breast cancer therapy.

Globally, among numerous cancer subtypes, breast cancer (BC) is one of the most prevalent forms of cancer affecting the female population. A female's family history significantly increases her risk of developing breast cancer. BC is caused by aberrant breast cells that proliferate and develop into tumors. It is estimated that 5-10% of breast carcinomas are inherited and involve genetic mutations that ensure the survival and prognosis of breast cancer cells. The most common genetic variations are responsible for hereditary breast cancer but are not limited to p53, BRCA1, and BRCA2. BRCA1 and BRCA2 are involved in genomic recombination, cell cycle monitoring, programmed cell death, and transcriptional regulation. When BRCA1 and 2 genetic variations are present in breast carcinoma, p53 irregularities become more prevalent. Both BRCA1/2 and p53 genes are involved in cell cycle monitoring. The present article discusses the current status of breast cancer research, spotlighting the tumor suppressor genes (BRCA1/2 and p53) along with structural activity relationship studies, FDA-approved drugs, and several therapy modalities for treating BC. Breast cancer drugs, accessible today in the market, have different side effects including anemia, pneumonitis, nausea, lethargy, and vomiting. Thus, the development of novel p53 and BRCA1/2 inhibitors with minimal possible side effects is crucial. We have covered compounds that have been examined subsequently (2020 onwards) in this overview which may be utilized as lead compounds. Further, we have covered mechanistic pathways to showcase the critical druggable targets and clinical and post-clinical drugs targeting them for their utility in BC.

Progress and Challenges in the Diagnosis and Treatment of Brain Cancer Using Nanotechnology.

Primary brain cancer or brain cancer is the overgrowth of abnormal or malignant cells in the brain or its nearby tissues that form unwanted masses called brain tumors. People with malignant brain tumors suffer a lot, and the expected life span of the patients after diagnosis is often only around 14 months, even with the most vigorous therapies. The blood-brain barrier (BBB) is the main barrier in the body that restricts the entry of potential chemotherapeutic agents into the brain. The chances of treatment failure or low therapeutic effects are some significant drawbacks of conventional treatment methods. However, recent advancements in nanotechnology have generated hope in cancer treatment. Nanotechnology has shown a vital role starting from the early detection, diagnosis, and treatment of cancer. These tiny nanomaterials have great potential to deliver drugs across the BBB. Beyond just drug delivery, nanomaterials can be simulated to generate fluorescence to detect tumors. The current Review discusses in detail the challenges of brain cancer treatment and the application of nanotechnology to overcome those challenges. The success of chemotherapeutic treatment or the surgical removal of tumors requires proper imaging. Nanomaterials can provide imaging and therapeutic benefits for cancer. The application of nanomaterials in the diagnosis and treatment of brain cancer is discussed in detail by reviewing past studies.

Application of PLGA as a Biodegradable and Biocompatible Polymer for Pulmonary Delivery of Drugs.

Pulmonary administration of biodegradable polymeric formulation is beneficial in the treatment of various respiratory diseases. For respiratory delivery, the polymer must be non-toxic, biodegradable, biocompatible, and stable. Poly D, L-lactic-co-glycolic acid (PLGA) is a widely used polymer for inhalable formulations because of its attractive mechanical and processing characteristics which give great opportunities to pharmaceutical industries to formulate novel inhalable products. PLGA has many pharmaceutical applications and its biocompatible nature produces non-toxic degradation products. The degradation of PLGA takes place through the non-enzymatic hydrolytic breakdown of ester bonds to produce free lactic acid and glycolic acid. The biodegradation products of PLGA are eliminated in the form of carbon dioxide (CO2) and water (H2O) by the Krebs cycle. The biocompatible properties of PLGA are investigated in various in vivo and in vitro studies. The high structural integrity of PLGA particles provides better stability, excellent drug loading, and sustained drug release. This review provides detailed information about PLGA as an inhalable grade polymer, its synthesis, advantages, physicochemical properties, biodegradability, and biocompatible characteristics. The important formulation aspects that must be considered during the manufacturing of inhalable PLGA formulations and the toxicity of PLGA in the lungs are also discussed in this paper. Additionally, a thorough overview is given on the application of PLGA as a particulate carrier in the treatment of major respiratory diseases, such as cystic fibrosis, lung cancer, tuberculosis, asthma, and pulmonary hypertension.

Dry powder inhalers of antitubercular drugs.

Despite advancements in the medical and pharmaceutical fields, tuberculosis remains a major health problem globally. Patients do not widely accept the conventional approach to treating tuberculosis (TB) due to prolonged treatment periods with multiple high doses of drugs and associated side effects. A pulmonary route is a non-invasive approach to delivering drugs, hormones, nucleic acid, steroids, proteins, and peptides directly to the lungs, improving the efficacy of the treatment and consequently decreasing the adverse effect of the treatment. This route has been successfully developed for the treatment of various respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), tuberculosis (TB), lung cancer, and other pulmonary infections. The major approaches of inhalation delivery systems include nebulizers, metered-dose inhalers (MDIs), and dry powder inhalers (DPIs). However, dry powder inhalers (DPIs) are more advantageous due to their stability and ability to deliver a high dose of the drug to the lungs. The present review analyzes the modern therapeutic approach of inhaled dry powders, with a special focus on novel drug delivery system (NDDS) based DPIs for the treatment of TB. The article also discussed the challenges of preparing inhalable dry powder formulations for the treatment of TB. The clinical development of inhalable anti-TB drugs is also reviewed.

Recent Advances in Transcranial Focused Ultrasound (FUS) Triggered Brain Delivery.

BACKGROUND: Successful delivery of therapeutic agents in the brain is very challenging, which makes treatment of various brain disorders very difficult. One of the major causes of this difficulty is the presence of physiological barriers in the brain like blood brain barrier (BBB) and blood cerebrospinal fluid (CSF) barrier. These barriers are very specific and restrict the entry of water soluble agents and ionized molecule. OBJECTIVE: The current article focuses on the transcranial route, transcranial focused ultrasound (FUS), and the techniques involved in transcranial focused ultrasound (FUS) delivery and recent updates of this system. RESULTS: The study describes that the FUS in conjunction with various other techniques opens the BBB very effectively. CONCLUSION: The administration of therapeutic agent using various FUS techniques opens a new perspective in treating CNS diseases.