ABSTRACT
Localized or topical administration of drugs may be considered as a potential approach for overcoming the problems caused by the various biological barriers encountered in drug delivery. The combination of using localized administration routes and delivering drugs in nanoparticulate formulations, such as liposomes, may have additional advantages. Such advantages include prolonged retention of high drug loads at the site of action and controlled release of the drug, ensuring prolonged therapeutic effect; decreased potential for side-effects and toxicity (due to the high topical concentrations of drugs); and increased protection of drugs from possible harsh environments at the site of action. The use of targeted liposomal formulations may further potentiate any acquired therapeutic advantages. In this review we present the most advanced cases of localized delivery of liposomal formulations of drugs, which have been investigated pre-clinically and clinically in the last ten years, together with the reported therapeutic advantages, in each case.
Subject(s)
Drug Carriers/administration & dosage , Drug Delivery Systems/methods , Liposomes/administration & dosage , Nanoparticles/administration & dosage , Administration, Intranasal/methods , Administration, Intranasal/trends , Administration, Intravaginal , Administration, Topical , Animals , Drug Carriers/metabolism , Drug Delivery Systems/trends , Humans , Injections, Intraocular/methods , Injections, Intraocular/trends , Liposomes/metabolism , Nanoparticles/metabolismSubject(s)
Dopamine Agonists/administration & dosage , Migraine Disorders/drug therapy , Serotonin 5-HT1 Receptor Agonists/administration & dosage , Administration, Inhalation , Administration, Intranasal/instrumentation , Administration, Intranasal/trends , Blood-Brain Barrier/metabolism , Dihydroergotamine/administration & dosage , Dopamine Agonists/pharmacokinetics , Humans , Metered Dose Inhalers , Oxazolidinones/administration & dosage , Serotonin 5-HT1 Receptor Agonists/pharmacokinetics , Tryptamines/administration & dosageABSTRACT
BACKGROUND: High flow nasal therapy (HFNT) is a technique in which humidified and heated gas is delivered to the airways through the nose via small nasal prongs at flows that are higher than the rates generally applied during conventional oxygen therapy. The delivered high flow rates combine mixtures of air and oxygen and enable different inspired oxygen fractions ranging from 0.21 to 1. HFNT is increasingly used in critically ill adult patients, especially hypoxemic patients in different clinical settings. MAIN BODY: Noninvasive ventilation delivers positive pressure (end-expiratory and inspiratory pressures or continuous positive airway pressure) via different external interfaces. In contrast, HFNT produces different physiological effects that are only partially linked to the generation of expiratory positive airway pressure. HFNT and noninvasive ventilation (NIV) are interesting non-invasive supports in perioperative medicine. HFNT exhibits some advantages compared to NIV because HFNT is easier to apply and requires a lower nursing workload. Tolerance of HFNT remains a matter of intense debate, and it may be related to selected parameters. Patients receiving HFNT and their respiratory patterns should be closely monitored to avoid delays in intubation despite correct oxygenation parameters. CONCLUSION: HFNT seems to be an interesting noninvasive support in perioperative medicine. The present review provides anesthesiologists with an overview of current evidence and practical advice on the application of HFNT in perioperative medicine in adult patients.
Subject(s)
Administration, Intranasal/methods , Noninvasive Ventilation/methods , Operating Rooms/methods , Oxygen Inhalation Therapy/methods , Patients' Rooms , Perioperative Care/methods , Administration, Intranasal/instrumentation , Administration, Intranasal/trends , Humans , Humidity , Intubation, Intratracheal/instrumentation , Intubation, Intratracheal/methods , Intubation, Intratracheal/trends , Nasal Cavity/drug effects , Nasal Cavity/physiology , Noninvasive Ventilation/instrumentation , Noninvasive Ventilation/trends , Operating Rooms/trends , Oxygen Inhalation Therapy/instrumentation , Oxygen Inhalation Therapy/trends , Patients' Rooms/trends , Perioperative Care/instrumentation , Perioperative Care/trendsABSTRACT
The neuropeptide oxytocin plays an evolutionarily conserved role in mammalian social behavior. Despite striking effects on animal social behavior after intracerebroventricular drug delivery, this delivery mode is impractical in humans. Intranasal oxytocin delivery provides a noninvasive alternative to increase central oxytocin activity, and has shown promise as a treatment for psychiatric illnesses. Intranasal oxytocin delivery is purported to increase central oxytocin concentrations via channels surrounding trigeminal and olfactory nerve fibers, which may facilitate increased activity at central oxytocin receptors. This report outlines the evidence for intranasal oxytocin delivery increasing central concentrations or activity, identifies current knowledge gaps and highlights future research opportunities. Recent efforts to enhance intranasal oxytocin delivery via improved intranasal delivery technology and dose-ranging studies are discussed.
Subject(s)
Brain/drug effects , Mental Disorders/drug therapy , Nasal Mucosa/metabolism , Oxytocin/administration & dosage , Absorption, Physiological , Administration, Intranasal/methods , Administration, Intranasal/trends , Animals , Behavior, Animal/drug effects , Brain/metabolism , Disease Models, Animal , Excipients/pharmacokinetics , Humans , Oxytocin/pharmacokinetics , Social BehaviorABSTRACT
Per G Djupesland, MD, PhD speaks to Hannah Makin, Commissioning Editor: Dr Djupesland is the inventor of OptiNose®'s patented, bi-directional nasal drug-delivery technology and is a Co-Founder of OptiNose AS. Dr. Djupesland is a lead inventor on all 38 OptiNose patent families/patent applications, and serves as Chief Scientific Officer of OptiNose AS, with primary responsibility for device discovery and early development efforts. These early development efforts include identifying new product opportunities that use bi-directional technology, advancing the design of devices using the bi-directional technology to treat a variety of medical conditions and conducting Phase I and IIa trials with new 'nose-to-brain' applications for the technology. Dr Djupesland is an otolaryngologist (ENT) with a specialization in rhinology and more than 25 years of clinical experience. Among other positions prior to OptiNose, he served as a Clinical Research Fellow at the Hospital for Sick Children and Toronto General in Toronto, Canada, primarily studying the role of nitric oxide in the upper airways. Dr Djupesland has authored more than 60 peer reviewed articles in international medical journals and has lectured at numerous international scientific conferences. He earned medical and doctorate degrees in the field of nasal physiology and aerodynamics from the University of Oslo.
Subject(s)
Administration, Intranasal/methods , Drug Delivery Systems/methods , Administration, Intranasal/trends , Drug Delivery Systems/trends , Exhalation , Humans , Nose/anatomy & histology , Patents as TopicABSTRACT
Objetivos. Analizar la situación actual de las investigaciones relacionadas con las nanopartículas poliméricas como sistemas de liberación de fármacos, así como los estudios que muestran las aplicaciones de fármacos incorporados en dichos sistemas y liberados en el sistema nervioso central mediante la administración intranasal. Métodos. Se utilizó, entre otras, como principal fuente la base de datos de la National Library of Medicine, Washington, DC (MEDLINE: PubMed) para realizar la búsqueda de artículos de investigación más importantes publicados sobre el tema. Resultados. Muchos de los fármacos utilizados para el tratamiento de enfermedades neurodegenerativas no son capaces de atravesar la barrera hematoencefálica (BHE) y llegar al cerebro en concentraciones suficientes para ejercer su efecto terapéutico. Es por ello que surge la idea de desarrollar nanopartículas poliméricas para ser administradas por vía nasal. Gracias a la utilización de dichos sistemas, numerosos estudios han puesto de manifiesto una mejora en la utilidad clínica del fármaco, permitiendo reducir la dosis y la frecuencia de dosificación a la vez que se reducen los efectos secundarios. Conclusiones. Pese a los avances realizados, demostrándose un aumento de la concentración de fármacos incorporados en sistemas nanoparticulados que llegan al cerebro, aún son necesarias investigaciones que solventen los problemas de toxicidad presentados por estos sistemas y su variabilidad de dosis absorbida
Objectives. The main objective of this study is to analyse the current researches related to polymeric nanoparticles as a system of drug delivery, as well as the studies that show the different ways in which the drugs included in this system and delivered into the central nervous system are apply through intranasal delivery. Methods. The elaboration of this study has required the exhaustive analysis of different scientific articles related to polymeric nanoparticles and drug delivery systems. The National Library of Medicine, Washington, DC (MEDLINE: PlubMed) has been the main source of information from which the scientific articles used to carry out this study have been selected. Results. Many of the drugs employed for the treatment of neurodegenerative diseases are not capable of going through the blood-brain-barrier (BBB) and reach the brain with enough concentration, being unable to apply their therapeutic effect. That is why the idea of developing polymeric nanoparticles to be delivered through nasal delivery come out. Thanks to the use of this system, many researches have shown an improvement in the clinical utility of the drug, reducing the dose and the frequency of dosing as well as the side effects. Conclusions. Despite the improvements in this field that demonstrate an increase in the concentration of drugs, included in the nanoparticles systems, that reaches the brain, it is still necessary to carry out researches in order to solve issues related to the toxicity and the variability in the absorbed dose that these systems present
Subject(s)
Humans , Male , Female , Nanoparticles/administration & dosage , Nanoparticles , Administration, Intranasal/instrumentation , Administration, Intranasal/methods , Administration, Intranasal , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Drug Delivery Systems/standards , Polymers/therapeutic use , Administration, Intranasal/standards , Administration, Intranasal/trends , Central Nervous System , Alzheimer Disease/drug therapy , Parkinson Disease/drug therapy , Depression/drug therapy , Schizophrenia/drug therapy , Headache/drug therapySubject(s)
Humans , Male , Female , Premedication/instrumentation , Premedication/methods , Premedication , Fentanyl/therapeutic use , Midazolam/therapeutic use , Administration, Intranasal/instrumentation , Administration, Intranasal/methods , Administration, Intranasal , Premedication/standards , Premedication/trends , Fentanyl/metabolism , Fentanyl/pharmacokinetics , Midazolam/metabolism , Midazolam/pharmacokinetics , Midazolam/standards , Administration, Intranasal/statistics & numerical data , Administration, Intranasal/standards , Administration, Intranasal/trendsABSTRACT
OBJETIVO: Conocer la efectividad y eficiencia del fentanilo intranasal en pectina comparado con otros tratamientos empleados en el dolor irruptivo oncológico a través de un análisis farmacoeconómico. RESULTADOS Y CONCLUSIONES: En la evaluación farmacoeconómica realizada, todas las opciones analizadas fueron coste-efectivas para una disposición a pagar (invertir) de 30.000 € por AVAC ganado (ratio coste/efectividad < 30.000 €). La opción más eficiente (mayor efectividad y menor coste) en todos los casos analizados es el espray intranasal de fentanilo en pectina (FPNS). En el análisis incremental, FPNS fue la opción dominante sobre todas las demás evaluadas: FST, OTFC, FBT e INFS. Del análisis de los datos de nuestro estudio de modelización de coste/efectividad del espray intranasal de fentanilo en pectina FPNS se concluye: - INFS sin proporcionar más eficacia ha demostrado ser significativamente más caro (+15 %). - FST, OTFC, FBT han demostrado una efectividad un 18 % menor que FPNS y además ser significativamente más caros (+9 %; +15 %; +10 %, respectivamente). Abreviaturas: AVAC: años ganados con buena calidad de vida. FPNS: PecFent®. FST: Abstral®. OTFC: Actiq®. FBT: Effentora®. INFS: Instanyl®
OBJECTIVE: Determine, with a pharmacoeconomic evaluation, the effectiveness and efficiency of fentanyl pectin intranasal spray for BTPc versus other indicated treatments. RESULTS AND CONCLUSIONS: All the treatments analyzed in the pharmacoeconomic evaluation were cost-effective in terms of a willingness to pay (invest) of € 30,000 per AVAC gained (cost / effectiveness ratio < € 30,000). The most efficient option (greater effectiveness and lower cost) of all the treatments analyzed was the fentanyl pectin nasal spray (FPNS). In the incremental analysis FPNS was the dominant treatment option over all the others evaluated: FST, OTFC, FBT and INFS. From the analysis of the data of our cost/effectiveness modeling study of the fentanyl pectin nasal spray, FPNS, we can conclude: - INFS without providing greater effectiveness has been shown to be significantly more expensive (+15 %). - FST, OTFC, FBT have demonstrated -18 % less effectiveness and also been shown to be significantly more expensive than FPNS (+9 %; +15 %; +10 %, respectively). Abbreviations: AVAC: Years gained with good quality of life. FPNS: PecFent®. FST: Abstral®. OTFC: Actiq®. FBT: Effentora®. INFS: Instanyl®
