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Journal of Nanobiotechnology Jul 2023It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best... (Review)
Review
It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use.
Topics: Humans; Pulmonary Fibrosis; Gold; Administration, Inhalation; COVID-19; Metal Nanoparticles; Drug Delivery Systems; Lung; Pharmaceutical Preparations; Nanoparticles
PubMed: 37422665
DOI: 10.1186/s12951-023-01971-7 -
Journal of Controlled Release :... Nov 2023The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of... (Review)
Review
The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of nanomedicine formulations. In contrast, while the oral route is the most favorable administration method for pharmaceuticals, little is known about the formation and composition of the corona formed by biomolecules on particles within the gastrointestinal tract. This work reviews the current literature understanding of (1) the formation of drug particles after oral administration, (2) the formation of a biomolecular corona within the gastrointestinal tract ("the gastrointestinal corona"), and (3) the possible implications of the formation of a gastrointestinal corona on the interactions of drug particles with their biological environment. In doing so, this work aims to establish the significance of the formation of a gastrointestinal corona in oral drug delivery to ultimately arrive at new avenues to control the behavior of orally administered pharmaceuticals.
Topics: Tissue Distribution; Nanoparticles; Gastrointestinal Tract; Administration, Oral; Pharmaceutical Preparations
PubMed: 37776905
DOI: 10.1016/j.jconrel.2023.09.049 -
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 -
Expert Opinion on Drug Delivery 2024Intravesical drug delivery (IDD) has gained recognition as a viable approach for treating bladder-related diseases over the years. However, it comes with its set of... (Review)
Review
INTRODUCTION
Intravesical drug delivery (IDD) has gained recognition as a viable approach for treating bladder-related diseases over the years. However, it comes with its set of challenges, including voiding difficulties and limitations in mucosal and epithelial penetration. These challenges lead to drug dilution and clearance, resulting in poor efficacy. Various strategies for drug delivery have been devised to overcome these issues, all aimed at optimizing drug delivery. Nevertheless, there has been minimal translation to clinical settings.
AREAS COVERED
This review provides a detailed description of IDD, including its history, advantages, and challenges. It also explores the physical barriers encountered in IDD, such as voiding, mucosal penetration, and epithelial penetration, and discusses current strategies for overcoming these challenges. Additionally, it offers a comprehensive roadmap for advancing IDD into clinical trials.
EXPERT OPINION
Physical bladder barriers and limitations of conventional treatments result in unsatisfactory efficacy against bladder diseases. Nevertheless, substantial recent efforts in this field have led to significant progress in overcoming these challenges and have raised important attributes for an optimal IDD system. However, there is still a lack of well-defined steps in the workflow to optimize the IDD system for clinical settings, and further research is required to establish more comprehensive in vitro and in vivo models to expedite clinical translation.
Topics: Administration, Intravesical; Drug Delivery Systems; Urinary Bladder; Pharmaceutical Preparations
PubMed: 38235592
DOI: 10.1080/17425247.2024.2307481 -
Drug Discovery Today Jun 2024Scientists around the globe have done cutting-edge research to facilitate the delivery of poorly absorbed drugs via various routes of administration and different... (Review)
Review
Scientists around the globe have done cutting-edge research to facilitate the delivery of poorly absorbed drugs via various routes of administration and different delivery systems. The vaginal route of administration has emerged as a promising mode of drug delivery, attributed to its anatomy and physiology. Novel drug delivery systems overcome the demerits of conventional systems via nanobiotechnology. This review will focus on the disorders associated with women that are currently targeted by vaginal drug delivery systems. In addition, it will provide insights into innovations in drug formulations for the general benefit of women.
Topics: Humans; Administration, Intravaginal; Drug Delivery Systems; Female; Animals; Vagina; Pharmaceutical Preparations
PubMed: 38705512
DOI: 10.1016/j.drudis.2024.104012 -
PeerJ 2024This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse... (Meta-Analysis)
Meta-Analysis
The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis.
BACKGROUND
This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse events when administering medications to premature infants with patent ductus arteriosus (PDA).
METHOD
The protocol for this review has been registered with PROSPERO (CRD 42022324598). We searched relevant studies in PubMed, Embase, Cochrane, and the Web of Science databases from March 26, 1996, to January 31, 2022.
RESULTS
A total of six randomized controlled trials (RCTs) and five observational studies were included for analysis, involving 630 premature neonates in total. Among these infants, 480 were in the ibuprofen group (oral intravenous routes), 78 in the paracetamol group (oral intravenous routes), and 72 in the ibuprofen group (rectal oral routes). Our meta-analysis revealed a significant difference in the rate of PDA closure between the the initial course of oral ibuprofen and intravenous ibuprofen groups (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.13-1.44]; < 0.0001, = 0%). In contrast, the meta-analysis of paracetamol administration via oral versus intravenous routes showed no significant difference in PDA closure rates (RR = 0.86, 95% CI [0.38-1.91]; = 0.71, = 76%). However, there was no statistically significant difference in the risk of adverse events or the need for surgical intervention among various drug administration methods after the complete course of drug therapy.
CONCLUSION
This meta-analysis evaluated the safety and effectiveness of different medication routes for treating PDA in premature infants. Our analysis results revealed that compared with intravenous administration, oral ibuprofen may offer certain advantages in closing PDA without increasing the risk of adverse events. Conversely, the use of paracetamol demonstrated no significant difference in PDA closure and the risk of adverse events between oral and intravenous administration.
Topics: Infant, Newborn; Humans; Ductus Arteriosus, Patent; Ibuprofen; Indomethacin; Cyclooxygenase Inhibitors; Infant, Low Birth Weight; Acetaminophen; Infant, Premature
PubMed: 38304184
DOI: 10.7717/peerj.16591 -
PloS One 2023Riluzole is the only treatment known to improve survival in patients with Amyotrophic Lateral Sclerosis (ALS). However, oral riluzole efficacy is modest at best, further...
Riluzole is the only treatment known to improve survival in patients with Amyotrophic Lateral Sclerosis (ALS). However, oral riluzole efficacy is modest at best, further it is known to have large inter-individual variability of serum concentration and clearance, is formulated as an oral drug in a patient population plagued with dysphagia, and has known systemic side-effects like asthenia (limiting patient compliance) and elevated liver enzymes. In this context, we postulated that continuous intrathecal (IT) infusion of low doses of riluzole could provide consistent elevations of the drug spinal cord (SC) concentrations at or above those achieved with oral dosing, without increasing the risk for adverse events associated with systemic drug exposure or off-target side effects in the brain. We developed a formulation of riluzole for IT delivery and conducted our studies in purpose-bred hound dogs. Our non-GLP studies revealed that IT infusion alone was able to increase SC concentrations above those provided by oral administration, without increasing plasma concentrations. We then conducted two GLP studies that combined IT infusion with oral administration at human equivalent dose, to evaluate SC and brain concentrations of riluzole along with assessments of safety and tolerability. In the 6-week study, the highest IT dose (0.2 mg/hr) was well tolerated by the animals and increased SC concentrations above those achieved with oral riluzole alone, without increasing brain concentrations. In the 6-month study, the highest dose tested (0.4 mg/hr) was not tolerated and yielded SC significantly above those achieved in all previous studies. Our data show the feasibility and safety profile of continuous IT riluzole delivery to the spinal cord, without concurrent elevated liver enzymes, and minimal brain concentrations creating another potential therapeutic route of delivery to be used in isolation or in combination with other therapeutics."
Topics: Humans; Animals; Dogs; Amyotrophic Lateral Sclerosis; Riluzole; Brain; Administration, Oral; Drug-Related Side Effects and Adverse Reactions
PubMed: 37607205
DOI: 10.1371/journal.pone.0277718 -
American Journal of Infection Control Dec 2023The aim of this study was to evaluate the impact of switch therapy of antimicrobials on cost reduction (pharmacoeconomic analysis) and hospital waste generation by... (Observational Study)
Observational Study
BACKGROUND
The aim of this study was to evaluate the impact of switch therapy of antimicrobials on cost reduction (pharmacoeconomic analysis) and hospital waste generation by switching from intravenous to oral therapy. This is a cross-sectional, observational, and retrospective study.
METHODS
Data from 2019, 2020, and 2021, provided by the clinical pharmacy service of a teaching hospital in the interior of Rio Grande do Sul, were analyzed. The variables analyzed were intravenous and oral antimicrobials, frequency, duration of use, and total treatment time according to the institutional protocols. An estimate of the amount of waste not generated from the change of administration route was calculated by weighing the kits using a precision balance in grams.
RESULTS
During the analyzed period, 275 switch therapy of antimicrobials were performed, resulting in US$ 55,256.00 of savings. The main antimicrobial classes that underwent changes were cephalosporins (25.1%), penicillins (22.55%), and quinolones (17.45%). Changing from intravenous to oral therapy avoided the generation of 170,631 g of waste, including needles, syringes, infusion bags, equipment, reconstituted solution bottles, and medication.
CONCLUSIONS
The change from intravenous to the oral route of antimicrobials is safe for the patient, economically effective, and significantly reduces waste generation.
Topics: Humans; Antimicrobial Stewardship; Economics, Pharmaceutical; Retrospective Studies; Cross-Sectional Studies; Anti-Infective Agents; Administration, Intravenous; Hospitals, Teaching
PubMed: 37295674
DOI: 10.1016/j.ajic.2023.06.003 -
BioDrugs : Clinical Immunotherapeutics,... Sep 2023Janus kinase inhibitor (JAKi) medications are small-molecule drugs that affect intracellular signal transduction. They are highly effective oral medications that have... (Review)
Review
Janus kinase inhibitor (JAKi) medications are small-molecule drugs that affect intracellular signal transduction. They are highly effective oral medications that have been approved for the treatment of various rheumatic diseases, with rheumatoid arthritis being a key example of an autoimmune rheumatic disease. JAKi are oral-route medications that are alternatives to injectable biologic therapies, launched in the late 1990s. While most safety concerns with JAKi are similar to the biologics, there are many differences. New data on comparative safety of JAKi versus tumor necrosis factor inhibitors (TNFi) were recently published that led to new black box warnings by the US Food and Drug Administration (FDA) about cardiovascular and cancer risks and a label change for JAKi. This review summarizes the current published data with regards to the safety of JAKi, focused on rheumatic diseases. Specifically, any risk differences between agents or across different indications are discussed, as well as the risk factors for these adverse outcomes.
Topics: Humans; Janus Kinase Inhibitors; Rheumatic Diseases; Arthritis, Rheumatoid; Biological Products; Administration, Oral; Antirheumatic Agents
PubMed: 37351790
DOI: 10.1007/s40259-023-00612-7 -
Clinical Microbiology and Infection :... Sep 2023
Topics: Humans; Administration, Intravenous; Anti-Bacterial Agents; Communicable Diseases; Administration, Oral; Infusions, Intravenous
PubMed: 37353077
DOI: 10.1016/j.cmi.2023.06.021