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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 -
Frontiers in Immunology 2023is the etiological agent of zoonotic visceral leishmaniasis (ZVL). The disease is endemic in Central and South America, Central and South East Asia, and the...
is the etiological agent of zoonotic visceral leishmaniasis (ZVL). The disease is endemic in Central and South America, Central and South East Asia, and the Mediterranean basin. Dogs are the main reservoir, with an estimated prevalence of approximately 2.5 million dogs in Southern Europe. Current treatments cause side effects, disease recurrence, and drug resistance. Therefore, the development of vaccines against canine leishmaniasis is necessary. We have generated a DNA vaccine based on the non-replicative antibiotic resistance marker-free plasmid vector pPAL that contains the encoding gene for the activated protein kinase C receptor analog (LACK). Homologous pPAL-LACK prime-boost intranasal administration confers efficacious protection in Beagle dogs with a reduction of clinical signs and a statistically significant reduction of the parasite burden in the bone marrow of more than 90% of dogs after experimental infection with highly infective promastigotes. This DNA vaccine elicits a robust cellular immune response skewed towards the Th1 profile.
Topics: Animals; Dogs; Vaccines, DNA; Administration, Intranasal; Leishmaniasis, Visceral; Genetic Vectors; Drug Resistance, Microbial
PubMed: 37790927
DOI: 10.3389/fimmu.2023.1213193 -
Drug Delivery Dec 2024Microneedle (MN) delivery devices are more accepted by people than regular traditional needle injections (e.g. vaccination) due to their simplicity and adaptability.... (Review)
Review
Microneedle (MN) delivery devices are more accepted by people than regular traditional needle injections (e.g. vaccination) due to their simplicity and adaptability. Thus, patients of chronic diseases like diabetes look for alternative pain-free treatment regimens circumventing regular subcutaneous injections. Insulin microneedles (INS-MNs) are a thoughtfully researched topic (1) to overcome needle phobia in patients, (2) for controlled delivery of the peptide, (3) decreasing the frequency of drug administration, (4) to ease the drug administration procedure, and (5) thus increasing patient adherence to the treatment dosage regimes. MNs physically disrupt the hard outer skin layer to create minuscule pores for insulin (INS) to pass through the dermal capillaries into the systemic circulation. Biodegradable polymeric MNs are of greater significance for INS and vaccine delivery than silicon, metal, glass, or non-biodegradable polymeric MNs due to their ease of fabrication, mass production, cost-effectiveness, and bioerodability. In recent years, INS-MNs have been researched to deliver INS through the transdermal implants, buccal mucosa, stomach wall, intestinal mucosal layers, and colonic mucosa apart from the usual transdermal delivery. This review focuses on the design characteristics and the applications of biodegradable/dissolvable polymeric INS-MNs in transdermal, intra-oral, gastrointestinal (GI), and implantable delivery. The prospective approaches to formulate safe, controlled-release INS-MNs were highlighted. Biodegradable/dissolvable polymers, their significance, their impact on MN morphology, and INS release characteristics were outlined. The developments in biodegradable polymeric INS-MN technology were briefly discussed. Bio-erodible polymer selection, MN fabrication and evaluation factors, and other design aspects were elaborated.
Topics: Humans; Insulin; Administration, Cutaneous; Drug Delivery Systems; Polymers; Injections, Subcutaneous; Needles; Skin
PubMed: 38147499
DOI: 10.1080/10717544.2023.2296350 -
Journal For Immunotherapy of Cancer Sep 2023Radiation therapy (RT) elicits DNA double-strand breaks, resulting in tumor cytotoxicity and a type I interferon (IFN) response via stimulator of interferon genes...
BACKGROUND
Radiation therapy (RT) elicits DNA double-strand breaks, resulting in tumor cytotoxicity and a type I interferon (IFN) response via stimulator of interferon genes (STING) activation. We investigated whether combining RT with an ataxia-telangiectasia mutated inhibitor promoted these effects and amplified tumor immunity.
METHODS
Mice-bearing syngeneic flank tumors (MOC2 head and neck squamous cell carcinoma or B78 melanoma) were treated with tumor-directed RT and oral administration of AZD0156. Specific immune cell depletion, type 1 interferon receptor 1 knock-out mice (IFNAR1-KO), and STING-deficient tumor cells were used to investigate tumor-immune crosstalk following RT and AZD0156 treatment.
RESULTS
Combining RT and AZD0156 reduced tumor growth compared with RT or AZD0156 alone in mice bearing MOC2 or B78 tumors. Low-dose AZD0156 (1-100 nM) alone did not affect tumor cell proliferation but suppressed tumor cell clonogenicity in combination with RT. Low-dose AZD0156 with RT synergistically increased IFN-β, major histocompatibility complex (MHC)-I, and programmed death-ligand 1 (PD-L1) expression in tumor cells. In contrast to wild-type mice, IFNAR1-KO mice showed reduced CD8+T cell tumor infiltration and poor survival following RT+AZD0156 treatment. CD8+T cell depletion reduced antitumor response during RT+AZD0156 treatment. STING-deficient MOC2 (MOC2-STING+/-) or B78 (B78-STING-/-) tumors eliminated the effects of RT+AZD0156 on the expression of IFN-β, MHC-I, and PD-L1, and reduced CD8+T cell infiltration and migration. Additional anti-PD-L1 therapy promoted antitumor response by elevation of tumor-MHC-I and lymphocyte activation.
CONCLUSIONS
Combined radiation and AZD0156 increase STING-dependent antitumor response. Tumor-derived cell-autonomous IFN-β amplification drives both MHC-I and PD-L1 induction at the tumor cell surface, which is required by anti-PD-L1 therapy to promote antitumor immune response following RT and AZD0156 combination therapy.
Topics: Animals; Mice; CD8-Positive T-Lymphocytes; Melanoma; Combined Modality Therapy; Administration, Oral; Cell Membrane
PubMed: 37730275
DOI: 10.1136/jitc-2023-007474 -
Clinical and Translational Science Dec 2023Immediate-release (IR) solid oral drug products constitute a significant portion of approved drug products and products under development. Bioequivalence (BE) assessment... (Review)
Review
Immediate-release (IR) solid oral drug products constitute a significant portion of approved drug products and products under development. Bioequivalence (BE) assessment for these oral products is important for establishing therapeutic equivalence for generic products to their respective comparator products. In December 2022, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published the first new draft guideline on BE for IR solid oral dosage forms (M13A). To support the development of ICH M13A, we comprehensively reviewed the landscape of oral IR products approved by the U.S. Food and Drug Administration (FDA) and compared BE recommendations for these products in the current U.S. FDA and European Medicines Agency (EMA) BE guidances. We utilized databases including Drugs@FDA, Orange Book, and product-specific guidances (PSGs) published on the U.S. FDA and EMA websites to collect information. Oral IR products account for 46% of all FDA-approved new drug applications currently listed in Orange Book with 82.5% solids, 0.9% semi-solids, and 16.6% liquids. For all published U.S. FDA PSGs for solid oral IR products, in vivo BE studies with pharmacokinetic (PK) endpoints account for 88% of BE approaches recommended. Of these PK BE studies, 86.5% recommended fasting and fed BE studies, while only 15.9% EMA PSGs recommended both fasting and fed BE studies. This review helps clarify the scope of U.S. solid oral IR products impacted by the new ICH M13A draft guideline and demonstrates how recommendations in draft ICH M13A could significantly harmonize BE recommendations for IR oral products to facilitate global drug development.
Topics: Humans; Therapeutic Equivalency; Drugs, Generic; Pharmaceutical Preparations; Drug Development; Administration, Oral
PubMed: 37904315
DOI: 10.1111/cts.13670 -
International Journal of Molecular... Apr 2024The past five decades have witnessed remarkable advancements in the field of inhaled medicines targeting the lungs for respiratory disease treatment. As a non-invasive... (Review)
Review
The past five decades have witnessed remarkable advancements in the field of inhaled medicines targeting the lungs for respiratory disease treatment. As a non-invasive drug delivery route, inhalation therapy offers numerous benefits to respiratory patients, including rapid and targeted exposure at specific sites, quick onset of action, bypassing first-pass metabolism, and beyond. Understanding the characteristics of pulmonary drug transporters and metabolizing enzymes is crucial for comprehending efficient drug exposure and clearance processes within the lungs. These processes are intricately linked to both local and systemic pharmacokinetics and pharmacodynamics of drugs. This review aims to provide a comprehensive overview of the literature on lung transporters and metabolizing enzymes while exploring their roles in exogenous and endogenous substance disposition. Additionally, we identify and discuss the principal challenges in this area of research, providing a foundation for future investigations aimed at optimizing inhaled drug administration. Moving forward, it is imperative that future research endeavors to focus on refining and validating in vitro and ex vivo models to more accurately mimic the human respiratory system. Such advancements will enhance our understanding of drug processing in different pathological states and facilitate the discovery of novel approaches for investigating lung-specific drug transporters and metabolizing enzymes. This deeper insight will be crucial in developing more effective and targeted therapies for respiratory diseases, ultimately leading to improved patient outcomes.
Topics: Humans; Administration, Inhalation; Lung; Membrane Transport Proteins; Animals; Pharmaceutical Preparations; Biological Transport
PubMed: 38731891
DOI: 10.3390/ijms25094671 -
International Journal of Biological... Dec 2023The critical role of oral colon-specific delivery systems (OCDDS) is important for delivering active agents to the colon and rectum specifically via the oral route. The... (Review)
Review
The critical role of oral colon-specific delivery systems (OCDDS) is important for delivering active agents to the colon and rectum specifically via the oral route. The use of micro/nanostructured OCDDS further improves drug stability, bioavailability, and retention time, leading to enhanced therapeutic effects. However, designing micro/nanoscale OCDDSs is challenging due to pH changes, enzymatic degradation, and systemic absorption and metabolism. Biodegradable natural polysaccharides are a promising solution to these problems, and β-glucan is one of the most promising natural polysaccharides due to its unique structural features, conformational flexibility, and specific processing properties. This review covers the diverse chemical structures of β-glucan, its benefits (biocompatibility, easy modification, and colon-specific degradation), and various β-glucan-based micro/nanosized OCDDSs, as well as their drawbacks. The potential of β-glucan offers exciting new opportunities for colon-specific drug delivery.
Topics: beta-Glucans; Colon; Drug Delivery Systems; Administration, Oral; Polysaccharides
PubMed: 37827417
DOI: 10.1016/j.ijbiomac.2023.127360 -
Behavioural Neurology 2023It has recently been shown that the administration of probiotics can modulate the microbiota-gut-brain axis and may have favorable effects in models of Parkinson's...
It has recently been shown that the administration of probiotics can modulate the microbiota-gut-brain axis and may have favorable effects in models of Parkinson's disease. In this study, we used a hemiparkinsonism model induced by the neurotoxin 6-OHDA to evaluate the efficacy of the administration of a four-week administration of a mixture containing the microorganisms LH01, LH03, and LH05. The hemiparkinsonism model induced an increase in rotations in the apomorphine test, along with a decrease in the latency time to fall in the rotarod test on days 14 and 21 after surgery, respectively. The administration of probiotics was sufficient to improve this condition. The model also showed a decrease in tyrosine hydroxylase immunoreactivity in the striatum and the number of labeled cells in the substantia nigra, both of which were counteracted by the administration of probiotics. The permeability of the blood-brain barrier was increased in the model, but this effect was reversed by the probiotics for both brain regions. The gut barrier was permeated with the model, and this effect was reversed and dropped to lower levels than the control group after the administration of probiotics. Finally, lipid peroxidation showed a pattern of differences similar to that of permeabilities. The inhibition of the permeability of the blood-brain and gut barriers mediated by the administration of probiotics will likely provide protection by downregulating oxidative stress, thus affecting the rotarod test performance.
Topics: Humans; Lactobacillus; Blood-Brain Barrier; Parkinsonian Disorders; Administration, Oral; Permeability
PubMed: 38025189
DOI: 10.1155/2023/6686037 -
International Journal of Nanomedicine 2024Given the unique physiological and pathological characteristics of the lung, the direct, inhalable route is more conducive to pulmonary drug delivery and disease control... (Review)
Review
Given the unique physiological and pathological characteristics of the lung, the direct, inhalable route is more conducive to pulmonary drug delivery and disease control than traditional systemic drug delivery, significantly circumventing drug loss, off-target effects, systemic and organ toxicity, etc., and is widely regarded as the preferred regimen for pulmonary drug delivery. However, very few lung diseases are currently treated with the preferred inhaled formulations, such as asthma, chronic obstructive pulmonary disease and pulmonary hypertension. And there is a lack of appropriate inhaled formulations for other critical lung diseases, such as lung cancer and pulmonary fibrosis, due to the fact that the physicochemical properties of the drugs and their pharmacokinetic profiles do not match the physiology of the lung, and conventional inhalation devices are unable to deliver them to the specific parts of the lung. Phytochemicals of natural origin, due to their wide availability and clear safety profile, hold great promise for the preparation of inhalable formulations to improve the current dilemma in the treatment of lung diseases. In particular, the preparation of inhalable formulations based on nano- and microparticulate carriers for drug delivery to deep lung tissues, which overcome the shortcomings of conventional inhalation therapies while targeting the drug activity directly to a specific part of the lung, may be the best approach to change the current dilemma of lung disease treatment. In this review, we discuss recent advances in nano- and micron-carrier-based inhalation formulations for the delivery of natural products for the treatment of pulmonary diseases, which may represent an opportunity for practical clinical translation of natural products.
Topics: Humans; Biological Products; Lung Diseases; Drug Delivery Systems; Lung; Administration, Inhalation; Pharmaceutical Preparations
PubMed: 38414528
DOI: 10.2147/IJN.S451206 -
Medicine Jun 2024Magnesium Sulfate (MgSO4) is a widely used adjuvant in anesthesia. Often administered with local anesthetics, it is known to reduce analgesic and opioid consumption... (Review)
Review
Magnesium Sulfate (MgSO4) is a widely used adjuvant in anesthesia. Often administered with local anesthetics, it is known to reduce analgesic and opioid consumption while extending the duration of analgesia. MgSO4 applications extend to orthopedic surgeries, cardiovascular and urogenital procedures, offering extended postoperative pain relief. While commonly administered through various routes, there is a research gap concerning the comparative efficacy of intrathecal (IT) and intravenous (IV) MgSO4 administration. This narrative review aims to provide a comparison between IT and IV administration of MgSO4 particularly following orthopedic procedures, where pain management is paramount. A comprehensive literature search was conducted across several electronic databases, trial registries, and gray literature from inception to 2023. Inclusion criteria encompassed studies investigating the effects of perioperative IT administration of magnesium compared to perioperative IV administration of MgSO4 in patients undergoing surgery, with no language restrictions. Our search identified 4326 articles, of which 9 randomized controlled trials met our inclusion criteria. We summarized these selected articles. Four studies discussed IT magnesium sulfate (MgSO4) administration, 2 focused on IT administration in orthopedic surgeries, and 3 explored both IV and IT administration of MgSO4 in orthopedic surgery. IT MgSO4 shows promise in postoperative pain management, delaying block onset and extending duration. Personalized administration choice, considering patient factors and surgery type, is crucial. Further research is needed to refine strategies for better patient outcomes, particularly following orthopedic surgeries.
Topics: Magnesium Sulfate; Humans; Pain, Postoperative; Orthopedic Procedures; Injections, Spinal; Administration, Intravenous; Pain Management; Analgesics
PubMed: 38875416
DOI: 10.1097/MD.0000000000038522