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Biomedicines Feb 2024In light of the unsuccessful traditional therapies for Parkinson's disease (PD) overmany years, there is an unmet need for the development of novel therapies to... (Review)
Review
In light of the unsuccessful traditional therapies for Parkinson's disease (PD) overmany years, there is an unmet need for the development of novel therapies to alleviate the symptoms of PD retardation or halt the progression of the disease itself. This systematic review aims to critically update some of the most promising novel treatments including gene therapy, cell-based therapies, targeted drug delivery, and neuroprotective agents, focusing on their challenges, limitations and future directions in PD research. Gene therapy in PD is encouraging, with AAV-based approaches targeting neurotrophic factors, dopamine production, and neuronal circuits in animal and clinical trials. A promising approach to targeted drug delivery for PD involves the use of nanotechnology to create drug delivery vehicles that can traverse the blood-brain barrier and deliver medications specifically to the regions of the brain affected by PD. Neuroprotective agents are compounds that have the ability to protect neurons from degeneration and death, and they hold great promise for the evolution of disease-modifying treatments for PD. Magnetic field therapy is a promising non-invasive method that promotes neural plasticity in PD. The establishment of standardized protocols for animal and human studies, safety, ethical considerations, and cost-effectiveness are the major challenges for the future research of novel PD therapies. The development of novel therapies for PD represents a promising path toward to effective personalized disease-modifying treatments for PD.
PubMed: 38540162
DOI: 10.3390/biomedicines12030549 -
Nanotheranostics 2023Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy....
Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) were developed in response to the need for materials with high thermal, chemical, and mechanical properties. The synthesis, ease of surface functionalization, tunable pore size, large surface area, and biocompatibility of MSNs make them useful in a variety of biomedical applications such as drug delivery, theranostics, and stem cell research. In addition, MSNs have a high capability of delivering actives ranging from small molecules such as drugs and amino acids to larger peptides, vaccines, and antibodies in general. Moreover, MSN-based transdermal delivery has sparked a lot of interest because of the increase in drug stability, permeation, and ease of functionalization. The functionalization of MSNs plays an important role in the efficient delivery of therapeutic agents in a highly controlled manner. This review introduced dermal and transdermal drug delivery systems, explained the anatomy of the skin, and summarized different barriers that affect the transdermal delivery of many therapeutic agents. In addition, the fundamentals of MSNs together with their physicochemical properties, synthesis approaches, raw materials used in their fabrication, and factors affecting their physicochemical properties will be covered. Moreover, the applications of MSNs in dermal and transdermal delivery, the biocompatibility of MSNs in terms of toxicity and safety, and biodistribution will be explained with the help of a detailed literature review. The review is covering the current and future perspectives of MSNs in the pharmaceutical field with therapeutic applications.
Topics: Drug Carriers; Drug Delivery Systems; Nanoparticles; Porosity; Silicon Dioxide; Tissue Distribution
PubMed: 36593800
DOI: 10.7150/ntno.77395 -
Pharmacological Reports : PR Oct 2022Drugs prescribed for psychiatric disorders in adolescence should be studied very extensively since they can affect developing and thus highly plastic brain differently... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Drugs prescribed for psychiatric disorders in adolescence should be studied very extensively since they can affect developing and thus highly plastic brain differently than they affect the adult brain. Therefore, we aimed to summarize animal studies reporting the behavioral consequences of chronic exposure to the most widely prescribed antidepressant drug among adolescents i.e., fluoxetine.
METHODS
Electronic databases (Medline via Pubmed, Web of Science Core Collection, ScienceDirect) were systematically searched until April 12, 2022, for published, peer-reviewed, controlled trials concerning the effects of chronic fluoxetine administration vs. vehicle on anxiety and depression measures in naïve and stress-exposed adolescent rodents. All of the relevant studies were selected and critically appraised, and a meta-analysis of eligible studies was performed.
RESULTS
A total of 18 studies were included in the meta-analysis. In naïve animals, chronic adolescent fluoxetine administration showed dose-related anxiogenic-like effects, measured as a reduction in time spent in the open arms of the elevated plus maze. No significant effects of chronic adolescent fluoxetine on depression-like behavior were reported in naïve animals, while in stress-exposed rodents chronic adolescent fluoxetine significantly decreased immobility time in the forced swim test compared to vehicle.
CONCLUSIONS
These results suggest that although chronic fluoxetine treatment proves positive effects in animal models of depression, it may simultaneously increase anxiety in adolescent animals in a dose-related manner. Although the clinical implications of the data should be interpreted with extreme caution, adolescent patients under fluoxetine treatment should be closely monitored.
Topics: Animals; Fluoxetine; Rodentia; Depression; Anxiety; Antidepressive Agents; Plastics; Behavior, Animal
PubMed: 36151445
DOI: 10.1007/s43440-022-00420-w -
Contact Lens & Anterior Eye : the... Feb 2024To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED). (Review)
Review
PURPOSE
To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED).
METHODS
A systematic review that included full-length randomized controlled studies (RCTs), as well as post hoc analyses of RCTs reporting new findings on OC-01 VNS treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included studies published between December 2021 and September 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected.
RESULTS
A total of 8 studies were included in this systematic review. OC-01 VNS treatment achieved higher improvement than vehicle in all reported variables. The mean differences between both groups were in favor of OC-01 VNS treatment and were as follow: eye dryness score base on a visual analogue scale (EDS-VAS) of -7.5 ± 2.2 points [-11.6 to -5.6], Schirmer test (ST) with anesthesia of 6.6 ± 2.3 mm [4.9 to 11.8] and total corneal fluorescein staining (tCFS) of -1.2 ± 0.01 points [-1.2 to -1.1]. Similar improvements were reported with OC-01 VNS 0.03 mg and 0.06 mg. Adverse events (AEs) were 15.5 ± 19.4 % [-13 to 80.5] higher in the OC-01 VNS group with an overall adherence > 93 %.
CONCLUSIONS
OC-01 VNS improves dry eye symptoms and signs with a satisfactory tolerability. Therefore, OC-01 VNS seems to be a safe and effective treatment that could be recommended in patients with DED. This new treatment could be particularly useful in those patients who have difficulties with the administration of traditional topical therapies.
Topics: Humans; Dry Eye Syndromes; Fluorescein; Nasal Sprays; Tears; Varenicline
PubMed: 38065797
DOI: 10.1016/j.clae.2023.102097 -
Nanomaterials (Basel, Switzerland) Sep 2021Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone... (Review)
Review
Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal to no toxicity or inflammatory response. This systematic review aims to provide an appraisal of the effectiveness of nHA as a delivery system for bone regeneration and whether the conjugation of proteins, antibiotics, or other bioactive molecules to the nHA further enhances osteogenesis in vivo. Out of 282 articles obtained from the literature search, only 14 articles met the inclusion criteria for this review. These studies showed that nHA was able to induce bone regeneration in various animal models with large or critical-sized bone defects, open fracture, or methicillin-resistant (MRSA)-induced osteomyelitis. The conjugations of drugs or bioactive molecules such as bone-morphogenetic protein-2 (BMP-2), vancomycin, calcitriol, dexamethasone, and cisplatin were able to enhance the osteogenic property of nHA. Thus, nHA is a promising delivery system for a variety of compounds in promoting bone regeneration in vivo.
PubMed: 34685010
DOI: 10.3390/nano11102569 -
Neuropsychopharmacology : Official... Mar 2022We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published...
We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published between 1960 and 2018, yielded a total of 146 papers reporting results from 901 studies. Relevant articles were those with any extractable data on phase resetting in wildtype (non-trait selected) rodents administered a drug, alongside a vehicle/control group, near or at the time of exposure. Most circadian pharmacology experiments were done using drugs thought to act directly on either the brain's central pacemaker, the suprachiasmatic nucleus (SCN), the SCN's primary relay, the retinohypothalamic tract, secondary pathways originating from the medial/dorsal raphe nuclei and intergeniculate leaflet, or the brain's sleep-arousal centers. While the neurotransmitter systems underlying these circuits were of particular interest, including those involving glutamate, gamma-aminobutyric acid, serotonin, and acetylcholine, other signaling modalities have also been assessed, including agonists and antagonists of receptors linked to dopamine, histamine, endocannabinoids, adenosine, opioids, and second-messenger pathways downstream of glutamate receptor activation. In an effort to identify drugs that unduly influence circadian responses to light, we quantified the net effects of each drug class by ratioing the size of the phase-shift observed after administration to that observed with vehicle in a given experiment. This allowed us to organize data across the literature, compare the relative efficacy of one mechanism versus another, and clarify which drugs might best suppress or potentiate phase resetting. Aggregation of the available data in this manner suggested that several candidates might be clinically relevant as auxiliary treatments to suppress ectopic light responses during shiftwork or amplify the circadian effects of timed bright light therapy. Future empirical research will be necessary to validate these possibilities.
Topics: Circadian Rhythm; Pharmaceutical Preparations; S Phase; Serotonin; Suprachiasmatic Nucleus
PubMed: 34961774
DOI: 10.1038/s41386-021-01251-8 -
Dermatology (Basel, Switzerland) 2022Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives.
OBJECTIVES
To assess the efficacy and safety of JAK inhibitors for AD treatment.
METHODS
We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator's Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI.
RESULTS
We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25-3.56, p < 0.001) and EASI score (WMD -28.82, 95% CI -34.48 to -23.16, p < 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66-4.84, p < 0.001) and EASI score (WMD -42.00, 95% CI -48.64 to -35.36, p < 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD -53.92, 95% CI -69.26 to -38.58, p < 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74-10.93, p < 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10-1.42, p = 0.001).
CONCLUSION
Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.
Topics: Dermatitis, Atopic; Eczema; Humans; Immunoglobulin A; Janus Kinase Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34455413
DOI: 10.1159/000518541 -
BioMed Research International 2021Animal models are well established for studying the effects of alkaloids in preventing myocardial ischemia-reperfusion injury. However, few studies have investigated the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Animal models are well established for studying the effects of alkaloids in preventing myocardial ischemia-reperfusion injury. However, few studies have investigated the therapeutic effects of alkaloids in humans. This meta-analysis and systematic review assessed the efficacy of alkaloids in attenuating infarct size in rats with myocardial ischemia-reperfusion injury.
METHODS
An integrated literature search including the PubMed, Embase, and Cochrane Library databases was performed to identify studies that evaluated the therapeutic effects of alkaloids on myocardial ischemia-reperfusion injury in rats. The main outcome was infarct size, and SYRCLE's risk of bias tool was used to assess the quality of the studies.
RESULTS
22 studies were brought into the meta-analysis. Compared with the effects of vehicle, alkaloids significantly reduced infarct size (standardized mean difference (SMD) = -0.45; 95% confidence interval (CI) = -0.64 to - 0.26). In subgroup analyses, isoquinoline alkaloids (SMD = -0.43; 95%CI = -0.70 to - 0.16) significantly reduced infarct size versus the control.
CONCLUSION
Isoquinoline alkaloids can potentially alleviate myocardial ischemia-reperfusion injury. This meta-analysis and systematic review supply a reference for research programs aiming to develop alkaloid-based clinical drugs. This trial is registered with CRD42019135489.
Topics: Alkaloids; Animals; Disease Models, Animal; Myocardial Reperfusion Injury; Rats
PubMed: 33791371
DOI: 10.1155/2021/6661526 -
Italian Journal of Dermatology and... Feb 2023Actinic keratosis (AK) is an intraepithelial tumor that, in most cases, arises in chronically sun-exposed areas. The combination of cryotherapy and photodynamic... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of the combination of cryotherapy and photodynamic modalities with imiquimod in patients with actinic keratosis: a systematic review and meta-analysis.
INTRODUCTION
Actinic keratosis (AK) is an intraepithelial tumor that, in most cases, arises in chronically sun-exposed areas. The combination of cryotherapy and photodynamic modalities with imiquimod has been proven to be a potential therapeutic option for AKs. However, there is no comprehensive systematic study that discussed this concept in literature taking into consideration both efficacy and safety.
EVIDENCE ACQUISITION
We performed a comprehensive search of the literature for studies assessing the efficacy and toxicity of the combinatorial tripartite regimen, consisting of cryotherapy and photodynamic modalities with imiquimod in AK. Metanalysis was performed using comprehensive meta-analysis version 3.0.
EVIDENCE SYNTHESIS
After the screening of 1031 studies, five studies were included. Two trials compared the effect of imiquimod/cryotherapy versus cryotherapy alone or versus cryotherapy/vehicle. Our meta-analysis indicated that imiquimod/cryotherapy effectively induces complete clinical clearance in patients with AKs (OR: 6.26; 95%CI: 1.56-24.1; P=0.01). Moreover, another two studies, which were not meta-analyzed, indicated a substantial clinical clearance in the number of AK lesions in the imiquimod plus photodynamic therapy arm as compared to 5% imiquimod or PDT alone. No serious systemic adverse events were reported in all the treatment arms.
CONCLUSIONS
Combined PDT or cryotherapy with imiquimod is more effective in the complete recovery of AK than treatment with imiquimod alone.
Topics: Humans; Imiquimod; Keratosis, Actinic; Aminoquinolines; Treatment Outcome; Cryotherapy
PubMed: 36799007
DOI: 10.23736/S2784-8671.22.07461-8 -
Clinical Parkinsonism & Related... 2022Parkinson's Disease (PD) is a progressive neurodegenerative condition associated with significant morbidity. Currently, there are limited pharmacological options and...
BACKGROUND
Parkinson's Disease (PD) is a progressive neurodegenerative condition associated with significant morbidity. Currently, there are limited pharmacological options and none of the therapies available are disease-modifying. This systematic review and -analysis considers a novel drug class through the research question - in pre-clinical rodent models of PD, is GLP-1 receptor agonist therapy neuroprotective when compared to vehicle controls?
METHODS
A literature search was conducted to locate relevant pre-clinical studies. Two separate outcomes were considered. The primary outcome was indicators of dopaminergic neurotransmission. The secondary outcome was indicators of motor symptoms. Untreated PD models were compared to PD-models treated with GLP-1 receptor agonists. The final -analysis was conducted using the Cochrane RevMan software and represented continuous data using the inverse variance statistical method and random effects analysis model. The final study statistic was represented as an SMD value with a p-value < 0.05 considered statistically significant. Study heterogeneity and publication bias was assessed using I values and funnel plots respectively.
RESULTS
Eleven studies fit the inclusion criteria and were included in the final analysis. For the primary outcome (n = 128), there was a statistically significant relative improvement of dopaminergic neurotransmission (SMD 1.71, 95% CI = 0.74-2.68, p = 0.0005, I = 76%). For the secondary outcome (n = 280), there was a statistically significant improvement in motor outcomes (SMD 2.11, 95% CI = 1.14-3.09, p < 0.0001, I = 89%).
CONCLUSIONS
GLP-1 receptor agonist therapy is neuroprotective in pre-clinical models of PD. This study provides the clinical foundation and research support for the design of rigorous clinical trials to further investigate these results in human PD populations.
PubMed: 35128376
DOI: 10.1016/j.prdoa.2022.100133