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British Journal of Hospital Medicine... Oct 2023Sinonasal inflammatory disease is very common and all clinicians who care for these patients should understand the topical treatment options available. This article... (Review)
Review
Sinonasal inflammatory disease is very common and all clinicians who care for these patients should understand the topical treatment options available. This article reviews the utility and application of steroidal, saline, decongestant, antihistamine and anticholinergic preparations for the treatment of sinonasal disease, with a particular focus on evidence-based guidelines for use in both specialist and non-specialist healthcare settings.
Topics: Humans; Nasal Sprays; Administration, Intranasal; Administration, Topical
PubMed: 37906068
DOI: 10.12968/hmed.2023.0212 -
Frontiers in Chemistry 2024Hydrogels are hydrophilic, three-dimensional, cross-linked polymers that absorb significant amounts of biological fluids or water. Hydrogels possess several favorable... (Review)
Review
Hydrogels are hydrophilic, three-dimensional, cross-linked polymers that absorb significant amounts of biological fluids or water. Hydrogels possess several favorable properties, including flexibility, stimulus-responsiveness, versatility, and structural composition. They can be categorized according to their sources, synthesis route, response to stimulus, and application. Controlling the cross-link density matrix and the hydrogels' attraction to water while they're swelling makes it easy to change their porous structure, which makes them ideal for drug delivery. Hydrogel in drug delivery can be achieved by various routes involving injectable, oral, buccal, vaginal, ocular, and transdermal administration routes. The hydrogel market is expected to grow from its 2019 valuation of USD 22.1 billion to USD 31.4 billion by 2027. Commercial hydrogels are helpful for various drug delivery applications, such as transdermal patches with controlled release characteristics, stimuli-responsive hydrogels for oral administration, and localized delivery via parenteral means. Here, we are mainly focused on the commercial hydrogel products used for drug delivery based on the described route of administration.
PubMed: 38476651
DOI: 10.3389/fchem.2024.1336717 -
Pharmaceuticals (Basel, Switzerland) Feb 2024The poor physicochemical properties of cannabidiol (CBD) hamper its clinical development. The aim of this review was to examine the literature to identify novel oral... (Review)
Review
The poor physicochemical properties of cannabidiol (CBD) hamper its clinical development. The aim of this review was to examine the literature to identify novel oral products and delivery strategies for CBD, while assessing their clinical implications and translatability. Evaluation of the published literature revealed that oral CBD strategies are primarily focused on lipid-based and emulsion solutions or encapsulations, which improve the overall pharmacokinetics (PK) of CBD. Some emulsion formulations demonstrate more rapid systemic delivery. Variability in the PK effects of different oral CBD products is apparent across species. Several novel administration routes exist for CBD delivery that may offer promise for specific indications. For example, intranasal administration and inhalation allow quick delivery of CBD to the plasma and the brain, whereas transdermal and transmucosal administration routes deliver CBD systemically more slowly. There are limited but promising data on novel delivery routes such as intramuscular and subcutaneous. Very limited data show that CBD is generally well distributed across tissues and that some CBD products enable increased delivery of CBD to different brain regions. However, evidence is limited regarding whether changes in CBD PK profiles and tissue distribution equate to superior therapeutic efficacy across indications and whether specific CBD products might be suited to particular indications.
PubMed: 38399459
DOI: 10.3390/ph17020244 -
Drug and Alcohol Dependence Reports Dec 2023Route of administration is an important pharmacokinetic variable in development of translationally relevant preclinical models. Humans primarily administer cannabis...
BACKGROUND
Route of administration is an important pharmacokinetic variable in development of translationally relevant preclinical models. Humans primarily administer cannabis through smoking, vaping, and edibles. In contrast, preclinical research has historically utilized injected Δ-tetrahydrocannabinol (THC). The present study sought to examine how route of administration affected the potency and time course of THC's discriminative stimulus properties.
METHODS
Adult female and male C57BL/6 mice were trained to discriminate intraperitoneal (i.p.) THC from vehicle in a drug discrimination procedure. After discrimination was acquired, a dose-effect curve was determined for i.p., oral (p.o.), subcutaneous (s.c.), and aerosolized THC. Subsequently, the time course of effects of each route of administration was determined.
RESULTS
THC administered i.p., p.o., s.c., or via aerosolization fully substituted for i.p. THC. The potency of THC's psychoactive effects was similar for i.p., p.o., and s.c., except that THC was more potent when administered s.c. vs p.o. in females. All routes of administration had a similar potency in both sexes. The duration of THC's psychoactive effects was similar across i.p., s.c., and p.o. routes of administration, whereas aerosolized THC produced a faster onset and shorter duration of effects compared to the other routes.
CONCLUSION
THC administered via multiple routes of administration, including those commonly used in preclinical research (i.p. and s.c.) and more translationally relevant routes (aerosol and p.o.), produced THC-like discriminative stimulus effects in mice trained to discriminate i.p. THC. More precise predictions of THC's effects in humans may result from use of these translationally relevant routes of administration.
PubMed: 38045495
DOI: 10.1016/j.dadr.2023.100205 -
Pharmaceutics Dec 2023Milnacipran is a dual serotonin and norepinephrine reuptake inhibitor, clinically used for the treatment of major depression or fibromyalgia. Currently, there are no...
Milnacipran is a dual serotonin and norepinephrine reuptake inhibitor, clinically used for the treatment of major depression or fibromyalgia. Currently, there are no studies reporting the pharmacokinetics (PK) of milnacipran after intraperitoneal (IP) injection, despite this being the primary administration route in numerous experimental studies using the drug. Therefore, the present study was designed to investigate the PK profile of IP-administered milnacipran in mice and compare it to the intravenous (IV) route. First a liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated to accurately quantify milnacipran in biological samples. The method was used to quantify milnacipran in blood and brain samples collected at various time-points post-administration. Non-compartmental and PK analyses were employed to determine key PK parameters. The maximum concentration (C) of the drug in plasma was at 5 min after IP administration, whereas in the brain, it was at 60 min for both routes of administration. Curiously, the majority of PK parameters were similar irrespective of the administration route, and the bioavailability was 92.5% after the IP injection. These findings provide insight into milnacipran's absorption, distribution, and elimination characteristics in mice after IP administration for the first time and should be valuable for future pharmacological studies.
PubMed: 38258064
DOI: 10.3390/pharmaceutics16010053 -
Journal of Nanobiotechnology Aug 2023Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a... (Review)
Review
Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a wide range of medications. However, oral drug delivery is limited by the poor oral bioavailability of many drugs, caused by extreme conditions and absorption challenges in the gastrointestinal tract. This review thoroughly discusses the targeted drug vehicles to the intestinal lymphatic system (ILS). It explores the structure and physiological barriers of the ILS, highlighting its significance in dietary lipid and medication absorption and transport. The review presents various approaches to targeting the ILS using spatially precise vehicles, aiming to enhance bioavailability, achieve targeted delivery, and reduce first-pass metabolism with serve in clinic. Furthermore, the review outlines several methods for leveraging these vehicles to open the ILS window, paving the way for potential clinical applications in cancer treatment and oral vaccine delivery. By focusing on targeted drug vehicles to the ILS, this article emphasizes the critical role of these strategies in improving therapeutic efficacy and patient outcomes. Overall, this article emphasizes the critical role of targeted drug vehicles to the ILS and the potential impact of these strategies on improving therapeutic efficacy and patient outcomes.
Topics: Humans; Pharmaceutical Preparations; Lymphatic System; Gastrointestinal Tract; Drug Delivery Systems; Biological Availability; Administration, Oral
PubMed: 37559085
DOI: 10.1186/s12951-023-01991-3 -
Advanced Drug Delivery Reviews Jul 2024Transdermal administration remains an active research and development area as an alternative route for long-acting drug delivery. It avoids major drawbacks of... (Review)
Review
Transdermal administration remains an active research and development area as an alternative route for long-acting drug delivery. It avoids major drawbacks of conventional oral (gastrointestinal side effects, low drug bioavailability, and need for multiple dosing) or parenteral routes (invasiveness, pain, and psychological stress and bio-hazardous waste generated from needles), thereby increasing patient appeal and compliance. This review focuses on the current state of long-acting transdermal drug delivery, including adhesive patches, microneedles, and molecularly imprinted polymeric systems. Each subsection describes an approach including key considerations in formulation development, design, and process parameters with schematics. An overview of commercially available conventional (adhesive) patches for long-acting drug delivery (longer than 24 h), the reservoir- and matrix-type systems under preclinical evaluation, as well as the advanced transdermal formulations, such as the core-shell, nanoformulations-incorporated and stimuli-responsive microneedles, and 3D-printed and molecularly imprinted polymers that are in development, is also provided. Finally, we elaborated on translational aspects, challenges in patch formulation development, and future directions for the clinical advancement of new long-acting transdermal products.
Topics: Humans; Administration, Cutaneous; Drug Delivery Systems; Delayed-Action Preparations; Animals; Transdermal Patch; Needles; Pharmaceutical Preparations
PubMed: 38692457
DOI: 10.1016/j.addr.2024.115326 -
MBio Oct 2023Many of the current pandemic threats are caused by viruses that infect the respiratory tract. Remarkably though, the majority of vaccines and antiviral drugs are...
Many of the current pandemic threats are caused by viruses that infect the respiratory tract. Remarkably though, the majority of vaccines and antiviral drugs are administered via alternative routes. In this perspective, we argue that the pulmonary route of administration deserves more attention in the search for novel therapeutic strategies against respiratory virus infections. Firstly, vaccines administered at the viral portal of entry can induce a broader immune response, employing the mucosal arm of the immune system; secondly, direct administration of antiviral drugs at the target site leads to superior bioavailability, enabling lower dosing and reducing the chance of side effects. We further elaborate on why the pulmonary route may induce a superior effect compared to the intranasal route of administration and provide reasons why dry powder formulations for inhalation have significant advantages over standard liquid formulations.
Topics: Humans; Antiviral Agents; Administration, Inhalation; Vaccines; Aerosols; Virus Diseases
PubMed: 37768057
DOI: 10.1128/mbio.01295-23 -
Water Research May 2024Monitoring cannabis consumption holds great interest due to the increasing trend towards its legalization for both medicinal and recreational purposes, despite the...
Monitoring cannabis consumption holds great interest due to the increasing trend towards its legalization for both medicinal and recreational purposes, despite the potential risks and harms involved. Wastewater-based surveillance (WBS) offers a valuable tool for assessing shifts and patterns in drug consumption and to evaluate law enforcement strategies and harm reduction programs. However, WBS-derived cannabis use estimates have been linked to greater uncertainties compared to other drugs, in part due to the many different routes of administration and a substantial excretion of metabolites in faecal matter. Therefore, the usual approach for estimating consumed amounts and scaling consumption compared to other problem drugs requires a rethink. This viewpoint highlights the progress made in this area and describes the current existing barriers related to in-sewer and in-sample behaviour (e.g., adsorption/desorption mechanisms), analytical procedures used (e.g., sample preparation), and pharmacokinetic aspects (e.g., administration route) linked to cannabis biomarkers in influent wastewater. These need to be addressed to improve the estimation of cannabis use and reflect spatial and temporal trends in the same way as for other drugs. Until then, we recommend being cautious when interpreting wastewater-based cannabis consumption estimates.
PubMed: 38552484
DOI: 10.1016/j.watres.2024.121522 -
Cell Death & Disease Sep 2023Hearing loss impacts the quality of life and affects communication resulting in social isolation and reduced well-being. Despite its impact on society and economy, no...
Hearing loss impacts the quality of life and affects communication resulting in social isolation and reduced well-being. Despite its impact on society and economy, no therapies for age-related hearing loss are available so far. Loss of mechanosensory hair cells of the cochlea is a common event of hearing loss in humans. Studies performed in birds demonstrating that they can be replaced following the proliferation and transdifferentiation of supporting cells, strongly pointed out on HCs regeneration as the main focus of research aimed at hearing regeneration. Neurotrophins are growth factors involved in neuronal survival, development, differentiation, and plasticity. NGF has been involved in the interplay between auditory receptors and efferent innervation in the cochlea during development. During embryo development, both NGF and its receptors are highly expressed in the inner ears. It has been reported that NGF is implicated in the differentiation of auditory gangliar and hair cells. Thus, it has been proposed that NGF administration can decrease neuronal damage and prevent hearing loss. The main obstacle to the development of hearing impairment therapy is that efficient means of delivery for selected drugs to the cochlea are missing. Herein, in this study NGF was administered by the intranasal route. The first part of the study was focused on a biodistribution study, which showed the effective delivery in the cochlea; while the second part was focused on analyzing the potential therapeutic effect of NGF in senescence-accelerated prone strain 8 mice. Interestingly, intranasal administration of NGF resulted protective in counteracting hearing impairment in SAMP8 mice, ameliorating hearing performances (analyzed by auditory brainstem responses and distortion product otoacoustic emission) and hair cells morphology (analyzed by microscopy analysis). The results obtained were encouraging indicating that the neurotrophin NGF was efficiently delivered to the inner ear and that it was effective in counteracting hearing loss.
Topics: Humans; Animals; Mice; Aged; Administration, Intranasal; Nerve Growth Factor; Quality of Life; Tissue Distribution; Hearing Loss; Deafness
PubMed: 37704645
DOI: 10.1038/s41419-023-06100-8