A comprehensive review on glucocorticoids induced osteoporosis: A medication caused disease.

Glucocorticoids (GCs) are steroid hormones that are extensively used in the treatment of autoimmune diseases, inflammation, and cancer. The major ill effect of administering GCs is that it has a deleterious effect on bone, which leads to GC-induced osteoporosis. GC therapy induces bone loss and is associated with the risk of nonvertebral and vertebral fractures, as it works in combination by increasing bone reabsorption and suppressing bone formation during the initial phase of therapy. It is seen and established that GC in excess or in low dose for 3 months or more can be a risk factor for fracture, and the risk increases with an increase in dose and duration of usage. The most common cause of secondary osteoporosis is the administration of GC inside the body to treat various diseases. The degree of bone loss is directly proportional to the GC dose and the exposure duration. The first step is to evaluate the patients' risk factors for the development of glucocorticoids that induce osteoporosis, which include the dose, duration of use, patient age, sex, previous fractures, and other medical conditions.

Exploring Nanocarriers as Treatment Modalities for Skin Cancer.

Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication.

Transethosomes: A Promising Challenge for Topical Delivery Short Title: Transethosomes for Topical Delivery.

Skin provides an excellent barrier to molecular transport, as the stratum corneum is the most formidable barrier to the passage of most pharmaceuticals. Various attempts have been made to improve drug administration into the body through intact skin. Though very few routes are as attractive as the topical route, drug transport through the skin is challenging. To overcome the challenges, researchers have found a system in which the drug is encapsulated into the vesicle, penetrating deeper into the skin to hit the target site. Vesicular systems like transethosome, an ultra- deformable vesicle (UDV), tend to accumulate in the skin layers. Since transethosomes have small particle size and can easily alter the shape of vesicles compared to other vesicular systems, they can penetrate through the layers of skin. Hence, the drug encapsulated into transethosomes can easily reach the target site. Transethosomes consist of ethanol and phospholipids along with an edge activator. Ethanol and edge activator help to enhance the skin permeation of transethosomes. Various methods of preparation of transethosomes, comparison of transethosomes with other lipid vesicles, characterization of transethosomes, and application of transethosomes have been covered in this review. Transethosomes can deliver a different variety of drugs, such as anticancer, corticosteroids, proteins and peptides, analgesics.

Exploring Liposomes for Lung Cancer Therapy.

Cancer is referred to as a pleiotropic disease-causing approximately 9.6 million deaths in 2018. Among all cancers, lung cancer was the leading cause of death in 2017, and 12% of fatalities were alone due to lung cancer. The associated risk factors in lung cancer include smoking (80-85%), chronic inflammation in the lungs, COPD, pulmonary fibrosis, environmental and occupational exposure to nickel, arsenic, chromates, etc. Early diagnosed patients' treatment plan includes chemotherapy, immunotherapy, radiotherapy, surgery, and tumor ablation. Many sorts of drug delivery carriers have been used in the past, usually in targeted chemotherapy. Liposomes are spherical shape vesicles containing a lipid bilayer and aqueous core, with potency to encapsulate both hydrophobic and hydrophilic drugs with minimal toxicity. These vesicles have a particle size of 0.02-1000 µm allowing selective passive targeting to the tumor's deeper tissues. Current publications on liposomes highlight their acceptance and best choice among all systems to deliver synthetic and herbal drugs to the lungs. This review focuses on many aspects, which include an in-depth analysis of potential anticancer drugs that have utilized the advantages of liposomes for effective lung carcinomatherapy and devices used to deliver the active agents to the pulmonary tissues. Investigations on ongoing, approved, and failed clinical trials and patents on products related to lung cancer have been highlighted to provide a critical review on the subject.

Neuroinflammation: A Potential Risk for Dementia.

Dementia is a neurodegenerative condition that is considered a major factor contributing to cognitive decline that reduces independent function. Pathophysiological pathways are not well defined for neurodegenerative diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in the brain contributing toward their pathology. Microglia of the central nervous system (CNS) are the principal components of the brain's immune defence system and can detect harmful or external pathogens. When stimulated, the cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, and nitrogen species in order to preserve the cell's microenvironment. These proinflammatory markers include cytokines such as IL-1, IL-6, and TNFα chemokines such as CCR3 and CCL2 and CCR5. Microglial cells may produce a prolonged inflammatory response that, in some circumstances, is indicated in the promotion of neurodegenerative diseases. The present review is focused on the involvement of microglial cell activation throughout neurodegenerative conditions and the link between neuroinflammatory processes and dementia.

Exploring Nanoemulsions for Prostate Cancer Therapy.

Prostate carcinoma is typical cancer. It is the second most common cancer globally. The estimated new cases in 2020 was 191 930 and estimated deaths was 33 330. Age, family history, & genetic factors are major factors that drive prostate cancer. Although, for treating metastatic disease, the major therapies available are radiation,bisphosphonate, and palliative chemotherapy. But the major drawback is therapy is disease-driven and later becomes metastatic and requires treatment. The ability to revolutionize cancer treatment by major targeting vehicles via the exploration of nanoemulsion suggests a potential for cancer treatment. The unique property of a biphasic liquid dosage form called nanoemulsion to reach leaky tumor vasculature is due to its nano-meter oil-droplet size of 20-200 nm. Recent reporting on nanoemulsions disclose their embracing and lay alternative for re-purposing herbal and synthetic drugs and their combination especially for targeting prostate cancer formulating an obtainable nanomedicine. So, this article emphasizes the use of nanoemulsions incorporating therapeutic agents for successful and targeted delivery for prostate cancer.

Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson's Disease Model.

PURPOSE: The present study is an attempt to develop a vitamin E loaded naringenin (NRG) Nanoemulsion (NE) for direct nose-to-brain delivery for better management of Parkinson's disease (PD). METHODS: The optimized NE was evaluated for efficacy in PD using multiple behavioral studies (including narrow beam test, muscular coordination test, grip strength test, forced swimming test, and akinesia test) in a rat model. Optimized formulation was evaluated for droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential, and viscosity. RESULTS: Optimized NE had a droplet size of 38.70 ± 3.11nm, PDI of 0.14 ± 0.0024, refractive index of 1.43 ± 0.01, transmittance of 98.12 ± 0.07 %, zeta potential of - 27.4 ± 0.14 mV, and viscosity of 19.67 ± 0.25 Pa s. Behavioral studies showed that 6-OHDA induced PD in rats were successfully reversed when administered with NRG NE intranasally along with the levodopa. While the levels of GSH and SOD were significantly higher, levels of MDA were significantly lower in the group treated with NRG NE via intranasal route along with levodopa. CONCLUSION: Encouraging results from current study provide evidence for possible efficacy of a novel noninvasive intranasal delivery system of NRG for management of PD related symptoms.

Adaptation of Quality by Design-Based Development of Isradipine Nanostructured-Lipid Carrier and Its Evaluation for In Vitro Gut Permeation and In Vivo Solubilization Fate.

The present study demonstrated the systematic adaptation of quality by design-integrated approach for the development of novel nanostructured lipid carrier (NLC) of an anti-hypertensive drug isradipine (ISD) to address the inherent challenges such as low solubility and low oral bioavailability. Plackett-Burman design was used for preliminary screening of significant process and formulation variables (p <0.05), which were further processed using Box-Behnken design for the attainment of optimization goal that is, mean particle size (85.7 ± 7.3 nm), drug entrapment efficiency (87.4 ± 3.29%), and in vitro drug release characteristics (92.89 ± 5.47%). The optimized ISD-NLC formulation also demonstrated well-dispersed uniform-shaped particles (polydispersity index 0.207 ± 0.029), high gastrointestinal fluid stability (zeta potential -10.17 ± 0.59 mV), and higher in vitro gut permeation (21.69 ± 2.38 µg/cm2 of ISD-NLC as compared to 11.23 ± 1.74 µg/cm2 in ISD suspension). Furthermore, lipolysis studies were performed for the purpose of in vivo fate, and significantly higher drug content of ISD from ISD-NLC in aqueous phase was found (72.34 ± 4.62%) as compared to drug suspension (3.01 ± 0.91%). Relative bioavailability of ISD-NLC and ISD suspension was increased by 4.2-fold and 1.78-fold in the absence and presence of cycloheximide which is a lymphatic uptake inhibitor revealing lymphatic uptake of ISD-NLC in bioavailability improvement. Hence, systematic adaptation of quality by design integrated approach improved gut permeation and potential solubilizaton fate (dynamic lipolysis) of ISD-NLC, which further improved the lymphatic uptake and biodistribution of drug thereby promisingits in vivo prospect and clinical efficacy.

Nanocarriers as treatment modalities for hypertension.

Hypertension, a worldwide epidemic at present, is not a disease in itself rather it is an important risk factor for serious cardiovascular disorders including myocardial infarction, stroke, heart failure, and peripheral artery disease. Though numerous drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of hypertension but they face substantial challenges regarding their bioavailability, dosing and associated adverse effects which greatly limit their therapeutic efficacies. Various studies have demonstrated that nanocarriers can significantly increase the drug bioavailability thereby reducing the frequency of dosing in addition to minimizing toxicity associated with high dose of the drug. The present review provides an insight into the challenges associated with the conventional antihypertensive formulations and need for oral nanoparticulate systems in order to overcome problems associated with conventional formulations. Hypertension has circadian pattern of blood pressure, therefore chronotherapeutics can play a decisive role for the treatment, and however, nanoparticulate system can play major role in hypertension management. Future prospective for particulate nanocarriers in drug delivery for hypertension includes chronotherapeutics and emerging technique like gene therapy which is also covered in the review.