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Clinical Microbiology and Infection :... Sep 2023The timing of the switch from intravenous (i.v.) to oral antibiotic therapy for orthopaedic bone and joint infections (BJIs) is debated. In this narrative article, we... (Review)
Review
OBJECTIVES
The timing of the switch from intravenous (i.v.) to oral antibiotic therapy for orthopaedic bone and joint infections (BJIs) is debated. In this narrative article, we discuss the evidence for and against an early switch in BJIs.
DATA SOURCES
We performed a PubMed and internet search investigating the association between the duration of i.v. treatment for BJI and remission of infection among adult orthopaedic patients.
CONTENT
Among eight randomized controlled trials and multiple retrospective studies, we failed to find any minimal duration of postsurgical i.v. therapy associated with clinical outcomes. We did not find scientific data to support the prolonged use of i.v. therapy or to inform a minimal duration of i.v.
THERAPY
Growing evidence supports the safety of an early switch to oral medications once the patient is clinically stable.
IMPLICATIONS
After surgery for BJI, a switch to oral antibiotics within a few days is reasonable in most cases. We recommend making the decision on the time point based on clinical criteria and in an interdisciplinary team at the bedside.
Topics: Adult; Humans; Administration, Intravenous; Administration, Oral; Anti-Bacterial Agents; Retrospective Studies; Randomized Controlled Trials as Topic
PubMed: 37182643
DOI: 10.1016/j.cmi.2023.05.008 -
Advanced Materials (Deerfield Beach,... Feb 2024Compared to injection administration, oral administration is free of discomfort, wound infection, and complications and has a higher compliance rate for patients with... (Review)
Review
Compared to injection administration, oral administration is free of discomfort, wound infection, and complications and has a higher compliance rate for patients with diverse diseases. However, oral administration reduces the bioavailability of medicines, especially biologics (e.g., peptides, proteins, and antibodies), due to harsh gastrointestinal biological barriers. In this context, the development and prosperity of nanotechnology have helped improve the bioactivity and oral availability of oral medicines. On this basis, first, the biological barriers to oral administration are discussed, and then oral nanomedicine based on organic and inorganic nanomaterials and their biomedical applications in diverse diseases are reviewed. Finally, the challenges and potential opportunities in the future development of oral nanomedicine, which may provide a vital reference for the eventual clinical transformation and standardized production of oral nanomedicine, are put forward.
Topics: Humans; Nanomedicine; Nanotechnology; Nanostructures; Pharmaceutical Preparations; Administration, Oral; Drug Delivery Systems
PubMed: 37724825
DOI: 10.1002/adma.202306081 -
Genes Dec 2023Globally, oral diseases are common, pose an economic burden, and significantly decline the quality of life of affected individuals. Recently, researchers have...
BACKGROUND
Globally, oral diseases are common, pose an economic burden, and significantly decline the quality of life of affected individuals. Recently, researchers have substantially highlighted the effect of depression on oral disease incidence and development. In this study, we elucidated the correlation between depression and oral diseases.
METHODS
Using two-sample Mendelian randomization (MR), the association between depression and the risk of 17 oral diseases was evaluated. Three methods were used to perform MR analysis: the inverse variance-weighted, weighted median, and MR-Egger methods. Furthermore, Cochran's Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test, and leave-one-out analysis were performed to analyze sensitivity.
RESULTS
After implementing multiple test corrections, we observed that genetic susceptibility to depression was associated with an increased risk of mouth ulcers, toothache, loose teeth, bleeding gums, painful gums, chronic periodontitis, chronic tonsil and adenoid diseases, peritonsillar abscess, and excessive tooth attrition. However, a causal relationship between depression and other oral diseases was not observed. Sensitivity analysis confirmed the robustness of the results.
CONCLUSIONS
We confirmed the causal relationship between depression and several oral diseases, thereby providing a novel viewpoint on the prevention and treatment of oral diseases. Our findings suggest the integration of depression control into routine clinical care to enhance the effectiveness of oral disease treatment.
Topics: Humans; Depression; Mendelian Randomization Analysis; Quality of Life; Administration, Oral; Causality
PubMed: 38137013
DOI: 10.3390/genes14122191 -
Veterinary Microbiology Aug 2023FIP is a fatal feline disease caused by FIPV. Two drugs (GS441524 and GC376) target FIPV and have good therapeutic effect when administered by subcutaneous injection....
FIP is a fatal feline disease caused by FIPV. Two drugs (GS441524 and GC376) target FIPV and have good therapeutic effect when administered by subcutaneous injection. However, subcutaneous injection has limitations compared with oral administration. Additionally, the oral efficacy of the two drugs has not been determined. Here, GS441524 and GC376 were shown to efficiently inhibit FIPV-rQS79 (recombination virus with a full-length field type I FIPV and the spike gene replaced with type II FIPV) and FIPV II (commercially available type II FIPV 79-1146) at a noncytotoxic concentration in CRFK cells. Moreover, the effective oral dose was determined via the in vivo pharmacokinetics of GS441524 and GC376. We conducted animal trials in three dosing groups and found that while GS441524 can effectively reducing the mortality of FIP subjects at a range of doses, GC376 only reducing the mortality rate at high doses. Additionally, compared with GC376, oral GS441524 has better absorption, slower clearance and a slower rate of metabolism. Furthermore, there was no significant difference between the oral and subcutaneous pharmacokinetic parameters. Collectively, our study is the first to evaluate the efficacy of oral GS441524 and GC376 using a relevant animal model. We also verified the reliability of oral GS441524 and the potential of oral GC376 as a reference for rational clinical drug use. Furthermore, the pharmacokinetic data provide insights into and potential directions for the optimization of these drugs.
Topics: Cats; Animals; Reproducibility of Results; Feline Infectious Peritonitis; Administration, Oral; Coronavirus, Feline
PubMed: 37269714
DOI: 10.1016/j.vetmic.2023.109781 -
Expert Opinion on Drug Delivery 2023Rapid advances in bioengineering enable the use of complex proteins as therapeutic agents to treat diseases. Compared with conventional small molecule drugs, proteins... (Review)
Review
INTRODUCTION
Rapid advances in bioengineering enable the use of complex proteins as therapeutic agents to treat diseases. Compared with conventional small molecule drugs, proteins have multiple advantages, including high bioactivity and specificity with low toxicity. Developing oral dosage forms with active proteins is a route to improve patient compliance and significantly reduce production costs. However, the gastrointestinal environment remains a challenge to this delivery path due to enzymatic degradation, low permeability, and weak absorption, leading to reduced delivery efficiency and poor clinical outcomes.
AREAS COVERED
This review describes the barriers to oral delivery of peptides and complex proteins, current oral delivery strategies utilized and the opportunities and challenges ahead to try and circumvent these barriers. Oral protein drugs on the market and clinical trials provide insights and approaches for advancing delivery strategies.
EXPERT OPINION
Although most current studies on oral protein delivery rely on and animal data, the safety and limitations of the approach in humans remain uncertain. The shortage of clinical data limits the development of new or alternative strategies. Therefore, designing appropriate oral delivery strategies remains a significant challenge and requires new ideas, innovative design strategies and novel model systems.
Topics: Animals; Humans; Drug Delivery Systems; Administration, Oral; Proteins; Peptides
PubMed: 37450427
DOI: 10.1080/17425247.2023.2237408 -
Biomaterials Nov 2023Biologics are unaffordable to a large majority of the global population because of prohibitively expensive fermentation systems, purification and the requirement for... (Review)
Review
Biologics are unaffordable to a large majority of the global population because of prohibitively expensive fermentation systems, purification and the requirement for cold chain for storage and transportation. Limitations of current production and delivery systems of biologics were evident during the recent pandemic when <2.5% of vaccines produced were available to low-income countries and ∼19 million doses were discarded in Africa due to lack of cold-chain infrastructure. Among FDA-approved biologics since 2015, >90% are delivered using invasive methods. While oral or topical drugs are highly preferred by patients because of their affordability and convenience, only two oral drugs have been approved by FDA since 2015. A newly launched oral biologic costs only ∼3% of the average cost of injectable biologics because of the simplified regulatory approval process by elimination of prohibitively expensive fermentation, purification, cold storage/transportation. In addition, the cost of developing a new biologic injectable product (∼$2.5 billion) has been dramatically reduced through oral or topical delivery. Topical delivery has the unique advantage of targeted delivery of high concentration protein drugs, without getting diluted in circulating blood. However, only very few topical drugs have been approved by the FDA. Therefore, this review highlights recent advances in oral or topical delivery of proteins at early or advanced stages of human clinical trials using chewing gums, patches or sprays, or nucleic acid drugs directly, or in combination with, nanoparticles and offers future directions.
Topics: Humans; Pharmaceutical Preparations; Administration, Topical; Proteins; Biological Products; Administration, Oral
PubMed: 37690380
DOI: 10.1016/j.biomaterials.2023.122312 -
Journal of Controlled Release :... Aug 2023Oral administration of pharmaceuticals is the most preferred route of administration for patients, but it is challenging to effectively deliver active ingredients (APIs)... (Review)
Review
Oral administration of pharmaceuticals is the most preferred route of administration for patients, but it is challenging to effectively deliver active ingredients (APIs) that i) have extremely high or low solubility in intestinal fluids, ii) are large in size, iii) are subject to digestive and/or metabolic enzymes present in the gastrointestinal tract (GIT), brush border, and liver, and iv) are P-glycoprotein substrates. Over the past decades, efforts to increase the oral bioavailability of APIs have led to the development of nanoparticles (NPs) with non-specific uptake pathways (M cells, mucosal, and tight junctions) and target-specific uptake pathways (FcRn, vitamin B12, and bile acids). However, voluminous findings from preclinical models of different species rarely meet practical standards when translated to humans, and API concentrations in NPs are not within the adequate therapeutic window. Various NP oral delivery approaches studied so far show varying bioavailability impacted by a range of factors, such as species, GIT physiology, age, and disease state. This may cause difficulty in obtaining similar oral delivery efficacy when research results in animal models are translated into humans. This review describes the selection of parameters to be considered for translational potential when designing and developing oral NPs.
Topics: Animals; Humans; Pharmaceutical Preparations; Nanoparticles; Administration, Oral; Biological Availability; Biological Transport; Intestinal Absorption; Drug Carriers
PubMed: 37348679
DOI: 10.1016/j.jconrel.2023.06.024 -
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 -
The Journal of Allergy and Clinical... Jul 2023
Topics: Humans; Food; Allergens; Food Hypersensitivity; Administration, Oral; Desensitization, Immunologic
PubMed: 37207800
DOI: 10.1016/j.jaci.2023.05.005 -
Therapeutic Delivery Aug 2023
Topics: Drug Delivery Systems; Liposomes; Brain; Administration, Oral
PubMed: 37535334
DOI: 10.4155/tde-2023-0049