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Journal of Thrombosis and Haemostasis :... May 2023Oral anticoagulation therapy has evolved beyond vitamin K antagonists to include oral direct thrombin inhibitors and factor Xa inhibitors. Collectively known as "direct...
Recommendation on the nomenclature for anticoagulants: updated communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Commitee on the Control of Anticoagulation.
Oral anticoagulation therapy has evolved beyond vitamin K antagonists to include oral direct thrombin inhibitors and factor Xa inhibitors. Collectively known as "direct oral anticoagulants," this class of medications represents the current standard of care for the prevention and treatment of common thrombotic disorders, including atrial fibrillation and venous thromboembolism. Medications that target factors XI/XIa and XII/XIIa are currently under investigation for several thrombotic and nonthrombotic conditions. Given that these emerging medications will likely have distinct risk-benefit profiles to the current direct oral anticoagulants, may have different routes of administration, and could be used for unique clinical conditions (e.g., hereditary angioedema), the International Society on Thrombosis and Haemostasis Subcommittee on Control of Anticoagulation assembled a writing group to make recommendations on the nomenclature of anticoagulant medications. With input from the broader thrombosis community, the writing group recommends that anticoagulant medications be described by the route of administration and specific targets (e.g., oral factor XIa inhibitor).
Topics: Humans; Anticoagulants; Antithrombins; Blood Coagulation; Thrombosis; Factor Xa Inhibitors; Hemostasis; Atrial Fibrillation; Administration, Oral
PubMed: 36796485
DOI: 10.1016/j.jtha.2023.02.008 -
Molecules (Basel, Switzerland) Apr 2020Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily... (Review)
Review
Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.
Topics: Administration, Intranasal; Animals; Blood-Brain Barrier; Central Nervous System Diseases; Drug Administration Routes; Drug Carriers; Drug Compounding; Drug Delivery Systems; Humans; Nanoparticles; Permeability; Theranostic Nanomedicine
PubMed: 32326318
DOI: 10.3390/molecules25081929 -
The Western Journal of Emergency... Mar 2021The intraosseous (IO) route is one of the primary means of vascular access in critically ill and injured patients. The most common sites used are the proximal humerus,... (Review)
Review
INTRODUCTION
The intraosseous (IO) route is one of the primary means of vascular access in critically ill and injured patients. The most common sites used are the proximal humerus, proximal tibia, and sternum. Sternal IO placement remains an often-overlooked option in emergency and prehospital medicine. Due to the conflicts in Afghanistan and Iraq the use of sternal IOs have increased.
METHODS
The authors conducted a limited review, searching PubMed and Google Scholar databases for "sternal IO," "sternal intraosseous," and "intraosseous" without specific date limitations. A total of 47 articles were included in this review.
RESULTS
Sternal IOs are currently FDA approved for ages 12 and older. Sternal IO access offers several anatomical, pharmacokinetic, hemodynamic, and logistical advantages over peripheral intravenous and other IO points of access. Sternal IO use carries many of the same risks and limitations as the humeral and tibial sites. Sternal IO gravity flow rates are sufficient for transfusing blood and resuscitation. In addition, studies demonstrated they are safe during active CPR.
CONCLUSION
The sternal IO route remains underutilized in civilian settings. When considering IO vascular access in adults or older children, medical providers should consider the sternum as the recommended IO access, particularly if the user is a novice with IO devices, increased flow rates are required, the patient has extremity trauma, or administration of a lipid soluble drug is anticipated.
Topics: Critical Illness; Emergency Medical Services; Humans; Infusions, Intraosseous; Risk Assessment; Sternum
PubMed: 34125048
DOI: 10.5811/westjem.2020.12.48939 -
Journal of Controlled Release :... Feb 2023Diseases affecting the anterior segment of the eye are the primary causes of vision impairment and blindness globally. Drug administration through the topical ocular... (Review)
Review
Diseases affecting the anterior segment of the eye are the primary causes of vision impairment and blindness globally. Drug administration through the topical ocular route is widely accepted because of its user/patient friendliness - ease of administration and convenience. However, it remains a significant challenge to efficiently deliver drugs to the eye through this route because of various structural and physiological constraints that restrict the distribution of therapeutic molecules into the ocular tissues. The bioavailability of topically applied ocular medications such as eye drops is typically less than 5%. Developing novel delivery systems to increase the retention time on the ocular surfaces and permeation through the cornea is one of the approaches adopted to boost the bioavailability of topically administered medications. Drug delivery systems based on nanotechnology such as micelles, nanosuspensions, nanoparticles, nanoemulsions, liposomes, dendrimers, niosomes, cubosomes and nanowafers have been investigated as effective alternatives to conventional ocular delivery systems in treating diseases of the anterior segment of the eye. This review discussed different nanotechnology-based delivery systems that are currently investigated for treating and managing diseases affecting the anterior ocular tissues. We also looked at the challenges in translating these systems into clinical use and the prospects of nanocarriers as a vehicle for the delivery of phytoactive compounds to the anterior segment of the eye.
Topics: Humans; Drug Delivery Systems; Eye Diseases; Eye; Nanotechnology; Liposomes; Cornea; Administration, Ophthalmic
PubMed: 36642250
DOI: 10.1016/j.jconrel.2023.01.018 -
Journal of Pharmaceutical Sciences Jan 2020The intradermal (ID) and subcutaneous (SC) routes are commonly used for therapeutic proteins (TPs) and vaccines; however, the bioavailability of TPs is typically less... (Review)
Review
The intradermal (ID) and subcutaneous (SC) routes are commonly used for therapeutic proteins (TPs) and vaccines; however, the bioavailability of TPs is typically less than small molecule drugs given via the same routes. Proteolytic enzymes in the dermal, SC, and lymphatic tissues may be responsible for the loss of TPs. In addition, the TPs may be exposed to reactive oxygen species generated in the SC tissue and the lymphatic system in response to injection-related trauma and impurities within the formulation. The reactive oxygen species can oxidize TPs to alter their efficacy and immunogenicity potential. Mechanistic understandings of the dominant proteolysis and oxidative routes are useful in the drug discovery process, formulation development, and to assess the potential for immunogenicity and altered pharmacokinetics (PK). Furthermore, in vitro tools representing the ID or SC and lymphatic system can be used to evaluate the extent of proteolysis of the TPs after the injection and before systemic entry. The in vitro clearance data may be included in physiologically based pharmacokinetic models for improved PK predictions. In this review, we have summarized various physiological factors responsible for proteolysis and oxidation of TPs after ID and SC administration.
Topics: Animals; Antibodies, Monoclonal; Glycoproteins; Humans; Injections, Intradermal; Injections, Subcutaneous; Lymphatic System; Oxidation-Reduction; Proteolysis; Reactive Oxygen Species
PubMed: 31408633
DOI: 10.1016/j.xphs.2019.08.005 -
Biomolecules May 2024Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration...
Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration route of MSC-sEVs affects their therapeutic efficacy in a mouse model of bleomycin (BLM)-induced skin scleroderma (SSc). We evaluated the impact of topical (TOP), subcutaneous (SC), and intraperitoneal (IP) administration of MSC-sEVs on dermal fibrosis, collagen density, and thickness. All three routes of administration significantly reduced BLM-induced fibrosis in the skin, as determined by Masson's Trichrome staining. However, only TOP administration reduced BLM-induced dermal collagen density, with no effect on dermal thickness observed for all administration routes. Moreover, SC, but not TOP or IP administration, increased anti-inflammatory profibrotic CD163 M2 macrophages. These findings indicate that the administration route influences the therapeutic efficacy of MSC-sEVs in alleviating dermal fibrosis, with TOP administration being the most effective, and this efficacy is not mediated by M2 macrophages. Since both TOP and SC administration target the skin, the difference in their efficacy likely stems from variations in MSC-sEV delivery in the skin. Fluorescence-labelled TOP, but not SC MSC-sEVs when applied to skin explant cultures, localized in the stratum corneum. Hence, the superior efficacy of TOP over SC MSC-sEVs could be attributed to this localization. A comparison of the proteomes of stratum corneum and MSC-sEVs revealed the presence of >100 common proteins. Most of these proteins, such as filaggrin, were known to be crucial for maintaining skin barrier function against irritants and toxins, thereby mitigating inflammation-induced fibrosis. Therefore, the superior efficacy of TOP MSC-sEVs over SC and IP MSC-sEVs against SSc is mediated by the delivery of proteins to the stratum corneum to reinforce the skin barrier.
Topics: Animals; Mesenchymal Stem Cells; Mice; Bleomycin; Extracellular Vesicles; Skin; Disease Models, Animal; Fibrosis; Female; Filaggrin Proteins; Macrophages; Drug Administration Routes; Humans
PubMed: 38927026
DOI: 10.3390/biom14060622 -
BioMed Research International 2022Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the... (Review)
Review
Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.
Topics: Administration, Intranasal; Administration, Oral; Drug Delivery Systems; Humans; Migraine Disorders; Serotonin 5-HT1 Receptor Agonists; Sumatriptan; Treatment Outcome
PubMed: 35075426
DOI: 10.1155/2022/3692065 -
Theranostics 2022The past few years has witnessed a booming market of protein and peptide drugs, owing to their superior efficiency and biocompatibility. Parenteral route is the most... (Review)
Review
The past few years has witnessed a booming market of protein and peptide drugs, owing to their superior efficiency and biocompatibility. Parenteral route is the most commonly employed method for protein and peptide drugs administration. However, short plasma half-life protein and peptide drugs requires repetitive injections and results in poor patient compliance. Oral delivery is a promising alternative but hindered by harsh gastrointestinal environment and defensive intestinal epithelial barriers. Therefore, designing suitable oral delivery systems for peptide and protein drugs has been a persistent challenge. This review summarizes the main challenges for oral protein and peptide drugs delivery and highlights the advanced formulation strategies to improve their oral bioavailability. More importantly, major intestinal cell types and available targeting receptors are introduced along with the potential strategies to target these cell types. We also described the multifunctional biomaterials which can be used to prepare oral carrier systems as well as to modulate the mucosal immune response. Understanding the emerging delivery strategies and challenges for protein and peptide drugs will surely inspire the production of promising oral delivery systems that serves therapeutic needs in clinical settings.
Topics: Administration, Oral; Drug Delivery Systems; Humans; Peptides; Pharmaceutical Preparations; Proteins
PubMed: 35154498
DOI: 10.7150/thno.61747 -
Expert Opinion on Drug Delivery Apr 2020: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by remodeling of small pulmonary arteries leading to increased pulmonary arterial... (Review)
Review
: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by remodeling of small pulmonary arteries leading to increased pulmonary arterial pressure. Existing treatments acts to normalize vascular tone via three signaling pathways: the prostacyclin, the endothelin-1, and the nitric oxide. Although over the past 20 years, there has been considerable progress in terms of treatments for PAH, the disease still remains incurable with a disappointing prognosis.: This review summarizes the pathophysiology of PAH, the advantages and disadvantages of the inhalation route, and assess the relative advantages various inhaled therapies for PAH. The recent studies concerning the development of controlled-release drug delivery systems loaded with available anti-PAH drugs have also been summarized.: The main obstacles of current pharmacotherapies of PAH are their short half-life, stability, and formulations, resulting in reducing the efficacy and increasing systemic side effects and unknown pathogenesis of PAH. The pulmonary route has been proposed for delivering anti-PAH drugs to overcome the shortcomings. However, the application of approved inhaled anti-PAH drugs is limited. Inhalational delivery of controlled-release nanoformulations can overcome these restrictions. Extensive studies are required to develop safe and effective drug delivery systems for PAH patients.
Topics: Administration, Inhalation; Animals; Antihypertensive Agents; Drug Delivery Systems; Humans; Pulmonary Arterial Hypertension
PubMed: 32070157
DOI: 10.1080/17425247.2020.1729119 -
Microbiology and Molecular Biology... May 2020The substantial discrepancy between the strong effects of functional foods and various drugs, especially traditional Chinese medicines (TCMs), and the poor... (Review)
Review
The substantial discrepancy between the strong effects of functional foods and various drugs, especially traditional Chinese medicines (TCMs), and the poor bioavailability of these substances remains a perplexing problem. Understanding the gut microbiota, which acts as an effective bioreactor in the human intestinal tract, provides an opportunity for the redefinition of bioavailability. Here, we discuss four different pathways associated with the role of the gut microbiota in the transformation of parent compounds to beneficial or detrimental small molecules, which can enter the body's circulatory system and be available to target cells, tissues, and organs. We further describe and propose effective strategies for improving bioavailability and alleviating side effects with the help of the gut microbiota. This review also broadens our perspectives for the discovery of new medicinal components.
Topics: Animals; Biological Availability; Drug Administration Routes; Gastrointestinal Microbiome; Humans; Medicine, Traditional; Mice; Pharmaceutical Preparations; Pharmacokinetics; Plants, Medicinal
PubMed: 32350027
DOI: 10.1128/MMBR.00072-19