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Topic Review
Mechanistically Coupled PK (MCPK) Model of Dabrafenib Metabolism
Dabrafenib inhibits the cell proliferation of metastatic melanoma with the oncogenic BRAF(V600)-mutation. However, dabrafenib monotherapy is associated with pERK reactivation, drug resistance, and consequential relapse. A clinical drug-dose determination study shows increased pERK levels upon daily administration of more than 300 mg dabrafenib. To clarify whether such elevated drug concentrations could be reached by long-term drug accumulation, the pharmacokinetics (MCPK) of dabrafenib and its metabolites were mechanistically coupled. The MCPK model is qualitatively based on in vitro and quantitatively on clinical data to describe occupancy-dependent CYP3A4 enzyme induction, accumulation, and drug–drug interaction mechanisms. The prediction suggests an eight-fold increase in the steady-state concentration of potent desmethyl-dabrafenib and its inactive precursor carboxy-dabrafenib within four weeks upon 150 mg b.d. dabrafenib. While it is generally assumed that a higher dose is not critical, it was found experimentally that a high physiological dabrafenib concentration fails to induce cell death in embedded 451LU melanoma spheroids.
  • 724
  • 29 Jan 2022
Topic Review
Two Non-Tablet Oral Formulations of L-Thyroxine
Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T4) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T4 replacement therapy includes all situations of unintended drug–drug and drug–food interactions as well as fasting conditions that are not necessarily respected by patients. The non-tablet L-T4 soft-gel capsules and solution have proven bioequivalence with the usual L-T4 tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. 
  • 724
  • 22 Jul 2022
Topic Review
Intrathecal Pseudodelivery of Drugs for Neurodegenerative Diseases
Intrathecal pseudodelivery of drugs is a novel route to administer medications to treat neurodegenerative diseases based on the cerebrospinal fluid (CSF)-sink therapeutic strategy by means of implantable devices. 
  • 723
  • 10 Mar 2023
Topic Review
Peripheralization Strategies Applied to Morphinans
Among therapeutically valuable opioids, morphinans are of the utmost clinical importance as analgesic drugs because of their agonistic actions to the mu-opioid receptor. They include powerful pain relieving agents, such as naturally occurring alkaloids (e.g., morphine and codeine), semisynthetic analogues (e.g., hydrocodone, hydromorphone, oxycodone, oxymorphone and buprenorphine), and synthetic derivatives (e.g., levorphanol).
  • 720
  • 29 Jun 2023
Topic Review
Treatment of  Rheumatoid Arthritis
Rheumatoid arthritis refers to joint diseases of unclear etiology whose final stages can lead to unbearable pain and complete immobility of the affected joints. Modern treatment with anti-inflammatory drugs, including janus kinase (JAK) inhibitors, monoclonal antibodies, and botanicals (polyphenols, glycosides, alkaloids, etc.) has achieved some success and hope for improving the course of the disease. 
  • 718
  • 30 Oct 2023
Topic Review
Cannabis for Potential Therapeutic Uses
Cannabis sativa has been utilized as a medicine and for recreational and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the cannabis plant, which is known for its psychotogenic and euphoric effects; the main psychotropic constituent of cannabis is Δ9-tetrahydrocannabinol (Δ9-THC). The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body. Cannabis is used as a therapeutic agent for treating pain and emesis. Some cannabinoids are clinically applied for treating chronic pain, particularly cancer and multiple sclerosis-associated pain, for appetite stimulation and anti-emesis in HIV/AIDS and cancer patients, and for spasticity treatment in multiple sclerosis and epilepsy patients. Medical cannabis varies from recreational cannabis in the chemical content of THC and cannabidiol (CBD), modes of administration, and safety. Despite the therapeutic effects of cannabis, exposure to high concentrations of THC, the main compound that is responsible for most of the intoxicating effects experienced by users, could lead to psychological events and adverse effects that affect almost all body systems, such as neurological (dizziness, drowsiness, seizures, coma, and others), ophthalmological (mydriasis and conjunctival hyperemia), cardiovascular (tachycardia and arterial hypertension), and gastrointestinal (nausea, vomiting, and thirst), mainly associated with recreational use. Cannabis toxicity in children is more concerning and can cause serious adverse effects such as acute neurological symptoms (stupor), lethargy, seizures, and even coma. 
  • 717
  • 29 Feb 2024
Topic Review
Hemorphins
Hemorphins are endogenous peptides that are also known as “non-classical” or “atypical” opioid peptides. They are produced under physiologicalor pathological(inflammation) states by hemoglobin proteolysis. They can be released from almost any of the hemoglobin chains (beta-, kappa-, delta-, or epsilon-chain) except the alpha chain.
  • 716
  • 09 Jul 2021
Topic Review
Mucosal DNA Vaccines Inoculated via the Airway
The highly vascularized URT is the primary route of ingress of inhaled pathogens. A dense network of mucosal-associated lymphoid tissues (MALTs) is in the mucosal tissues to help induce pathogen-specific immune responses, reducing occurrences of infections. 
  • 716
  • 29 Mar 2022
Topic Review
Cannabis and Multiple Sclerosis-Related Symptoms
Multiple sclerosis (MS) is known as an autoimmune disease that damages the neurons in the central nervous system. MS is characterized by its most common symptoms of spasticity, muscle spasms, neuropathic pain, tremors, bladder dysfunction, dysarthria, and some intellectual problems, including memory disturbances. Several clinical studies have been conducted to investigate the effects of cannabis on the relief of these symptoms in MS patients.
  • 715
  • 12 May 2022
Topic Review
Diet, Obesity, and Depression
Obesity and depression co-occur in a significant proportion of the population. Mechanisms linking the two disorders include the immune and the endocrine system, psychological and social mechanisms. 
  • 710
  • 12 May 2021
Topic Review
Phase II Drug-Metabolizing Enzyme and Drug Transporter Expression
Sparse and conflicting evidence exists regarding the localization, expression, and regulation of phase II drug-metabolizing enzymes and drug transporters across gestational stages. To resolve the uncertainties and assumptions in current knowledge, additional pharmacokinetic (PK) data and clinical pharmacology research are required to understand drug metabolism and transport in the pregnant woman and in the placenta.
  • 710
  • 29 Dec 2023
Topic Review
Phytomedicines Targeting Cancer Stem Cells
Phytomedicines exist either in isolated or purified form or as a mixture of different secondary metabolites, and are used to prevent and cure different diseases. Phytomedicines may also have vitamins and minerals which are believed to synergize preventive and therapeutic effects, and additionally be useful in treatment of drug-resistant cancers.
  • 709
  • 25 Oct 2021
Topic Review
Herbal Treatments for Breast Cancer
Breast cancer is a complex disease for which pharmacological treatment does not guarantee success or cure. Plants possess phytochemical components with antioxidant and anti-inflammatory properties, mainly coumarins, flavonoids, alkaloids, and terpenoids. Several studies have demonstrated that bioactive compounds from plants can exert anti-tumor activity through various signaling pathways, such as apoptosis, autophagy, modification of the tumor microenvironment, cell arrest, and the suppression of angiogenesis.
  • 708
  • 13 Oct 2023
Topic Review
Applications of Alginates
Alginates (ALG) have been used in biomedical and pharmaceutical technologies for a long time. ALG are natural polymers occurring in brown algae and feature multiple advantages, including biocompatibility, low toxicity and mucoadhesiveness. Moreover, ALG demonstrate biological activities per se, including anti-hyperlipidemic, antimicrobial, anti-reflux, immunomodulatory or anti-inflammatory activities. ALG are characterized by gelling ability, one of the most frequently utilized properties in the drug form design. ALG have numerous applications in pharmaceutical technology that include micro- and nanoparticles, tablets, mucoadhesive dosage forms, wound dressings and films. However, there are some shortcomings, which impede the development of modified-release dosage forms or formulations with adequate mechanical strength based on pure ALG. Other natural polymers combined with ALG create great potential as drug carriers, improving limitations of ALG matrices. 
  • 707
  • 06 Jan 2023
Topic Review
Immunomodulatory Properties of Nigella sativa Seed Extracts
For thousands of years till nowadays, Nigella sativa (NS) has served as a common spice and food preservative. Its seed extracts, seed oil, and essential oil in traditional medicine have been used to remedy many ailments such as headaches, fever, gastric complaints, and even rheumatism. In addition, the antibacterial, virucidal, fungicidal, and antiparasitic properties of NS are well known. However, studies on the possible immunomodulatory effects of black cumin are relatively scarce.
  • 707
  • 06 Jul 2023
Topic Review
Nanovesicles for Enhanced Drug Delivery
Liposomes are the classic and first investigated phospholipid vesicles. These are rigid nanovesicles, and their ability to enhance drug permeability to the deeper skin layers is limited. 
  • 705
  • 22 Feb 2024
Topic Review
Phytochemicals and Parkinson’s Disease
Complementary therapies and phytonutrients derived from plant sources have been proposed as treatments for Parkinson’s disease. Numerous natural phytochemicals have emerged as therapeutically interesting compounds, drug entities, and phytochemicals for the treatment of inflammatory disorders. Additionally, numerous pharmacological studies have shown that phytochemicals are useful in treating neurodegenerative diseases (NDDs), depression, and dementia.
  • 704
  • 10 Jul 2023
Topic Review
Fluorescence Microscopy Techniques and DDS
In the latest years, fluorescence microscopy-related techniques have exhibited continuous developments and progresses, both from technical and applicative perspectives, holding the promise to provide unprecedented tools for drug delivery research.We have revised the major fluorescence microscopy-related experimental techniques available for the characterization of drug delivery systems （DDS）from static and dynamic points of view in different media, with a particular focus on the investigation within biological environments and in vivo. Indeed, the opportunities provided by fluorescence microscopy-related techniques to disentangle scientific issues typical of drug delivery research (spanning from the colloidal characterization of a DDS to its adhesion to biological membranes, its interaction with biomolecules, and its intracellular behavior) are countless and exponentially growing, allowing for the expectation that in the next few years the development of completely new tools and protocols will truly advance drug delivery research.
  • 703
  • 22 Jun 2021
Topic Review
Extracellular Vesicles-Loaded Microneedle Technology
Microneedles (MNs), renowned for their painless and minimally invasive qualities, exhibit significant potential for facilitating effective drug delivery, vaccination, and targeted sample extraction. Extracellular vesicles (EVs), serving as cargo for MNs, are naturally occurring nanovesicles secreted by cells and characterized by novel biomarkers, low immunogenicity, and cell-source-specific traits. MNs prove instrumental in extracting EVs from the sample fluid, thereby facilitating a promising diagnostic and prognostic tool. To harness the therapeutic potential of EVs in tissue repair, MNs with sustained delivery of EVs leverage micron-sized channels to enhance targeted site concentration, demonstrating efficacy in treating various diseases, such as Achillea tendinopathy, hair loss, spinal cord injury, and diabetic ulcers. EV-loaded MNs emerge as a promising platform for repair applications of skin, cardiac, tendon, hair, and spinal cord tissues.
  • 702
  • 18 Mar 2024
Topic Review
Molecules for Glioblastoma Therapy
Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor. The current standard of care for GBM is the Stupp protocol which includes surgical resection, followed by radiotherapy concomitant with the DNA alkylator temozolomide; however, survival under this treatment regimen is an abysmal 12–18 months. New and emerging treatments include the application of a physical device, non-invasive ‘tumor treating fields’ (TTFs), including its concomitant use with standard of care; and varied vaccines and immunotherapeutics being trialed. Some of these approaches have extended life by a few months over standard of care, but in some cases are only available for a minority of GBM patients. Extensive activity is also underway to repurpose and reposition therapeutics for GBM, either alone or in combination with the standard of care. 
  • 701
  • 19 Feb 2021
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