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Current Drug Delivery 2017In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore... (Review)
Review
BACKGROUND
In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore aims at summarizing various methods of nano-emulsion formulation and their use as a topical and transdermal delivery vehicle for a number of active pharmaceutical ingredients from different pharmacological classes.
METHODS
This article represents a systematic review of nano-emulsions for topical and transdermal drug delivery. A vast literature was searched and critically analysed.
RESULTS
Nano-emulsions are thermokinetically stable dispersion systems, which have been used in topical and transdermal delivery of a number of pharmaceutically active compounds. Nano-emulsions have a narrow droplet size range with tuneable surface properties, which make them an ideal delivery vehicle. Nanoemulsions have a number of advantages over conventional emulsions, including easy preparation using various low and high energy methods, optical transparency, high solubilisation capacity, high stability to droplet aggregation and the ability to penetrate the skin; thus allowing the transdermal delivery of drugs.
CONCLUSION
This review indicated that nano-emulsions are promising vehicle for entrapping various drugs and are suitable for traversing the skin barrier for systemic effects.
Topics: Administration, Cutaneous; Chemistry, Pharmaceutical; Emulsions; Humans; Nanoparticles; Skin; Skin Absorption
PubMed: 27557672
DOI: 10.2174/1567201813666160824125444 -
Expert Opinion on Drug Safety Aug 2014Transdermal patches provide an attractive route of drug delivery with considerable advantages over other routes of administration, for example maintenance of constant... (Review)
Review
INTRODUCTION
Transdermal patches provide an attractive route of drug delivery with considerable advantages over other routes of administration, for example maintenance of constant plasma drug levels and convenient usage. However, medication administration errors abound with this dosage form and frequently result in harm or treatment failure.
AREAS COVERED
A systematic literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using appropriate keywords to identify articles reporting faulty transdermal patch administration. Common pitfalls and errors that were identified through the systematic literature search were discussed alongside individual steps of the transdermal patch administration process.
EXPERT OPINION
The systematic investigation of published errors illustrated that every step in the transdermal patch administration process is prone to errors. Thereby, the lack of knowledge and awareness of the importance of a correct administration practice were a major source of risk. Based on the identified errors and causes of errors prevention strategies were developed as a first step in avoiding transdermal patch administration errors.
Topics: Administration, Cutaneous; Drug Delivery Systems; Drug-Related Side Effects and Adverse Reactions; Humans; Medication Errors; Pharmaceutical Preparations; Transdermal Patch
PubMed: 24921682
DOI: 10.1517/14740338.2014.926888 -
Medicine Sep 2023A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage. (Meta-Analysis)
Meta-Analysis
BACKGROUND
A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage.
METHODS
Electronic databases (Pubmed, Embase, Web of Science and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different administration route of nimodipine (intravenous and enteral) versus placebo for treatment subarachnoid hemorrhage. Outcomes included case fatality at 3 months, poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), incidence of delayed cerebral ischemia (DCI), delayed ischemic neurological deficit. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
Nine randomized controlled trials met criteria for inclusion and finally included in this NMA. There was no statistically significant between intravenous and enteral in terms of case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P > .05). Both intravenous and enteral could reduce case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P < .05). The SUCRA shows that enteral ranked first, intravenous ranked second and placebo ranked the last for case fatality, the occurrence of DCI and poor outcomes. The SUCRA shows that intravenous ranked first, enteral ranked second and placebo ranked the last for delayed ischemic neurologic deficit.
CONCLUSIONS
It is possible that both enteral and intravenous nimodipine have comparable effectiveness in preventing poor outcomes, DCI, and delayed ischemic neurological deficits. However, further investigation may be necessary to determine the exact role of intravenous nimodipine in current clinical practice.
Topics: Humans; Nimodipine; Subarachnoid Hemorrhage; Network Meta-Analysis; Bayes Theorem; Administration, Intravenous; Brain Ischemia; Cerebral Infarction
PubMed: 37773855
DOI: 10.1097/MD.0000000000034789 -
British Medical Bulletin Sep 2023It is unclear whether hydrodilatation is beneficial in the management of frozen shoulder compared with other common conservative management modalities. This systematic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
It is unclear whether hydrodilatation is beneficial in the management of frozen shoulder compared with other common conservative management modalities. This systematic review evaluates the efficacy of hydrodilatation for the management of frozen shoulder.
SOURCES OF DATA
A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An extensive search of PubMed, Embase, Scopus, Cochrane Central, Web of Science and CINAHL databases using multiple keyword combinations of 'shoulder', 'rotator', 'adhesive capsulitis', 'hydrodilatat*', 'distension' since inception of the databases to June 2023 was implemented.
AREAS OF AGREEMENT
Hydrodilatation leads to at least transient more marked improvements in shoulder disability and passive external rotation compared with intra-articular corticosteroid injections.
AREAS OF CONTROVERSY
Hydrodilatation improves passive external rotation in the longer term. Moreover, hydrodilatation may be a preferable option over manipulation under anaesthesia, given its lower cost and better patient convenience.
GROWING POINTS
Intensive mobilization after hydrodilatation is a promising adjuvant treatment option for patients suffering from a frozen shoulder.
AREAS TIMELY FOR DEVELOPING RESEARCH
Although current evidence suggests that hydrodilatation provides a transient improvement in disability in patients with frozen shoulder, its clinical relevance remains unclear. Further research is necessary to establish its role in the management of the condition.
Topics: Humans; Shoulder Joint; Bursitis; Adrenal Cortex Hormones; Injections, Intra-Articular; Anesthesia; Range of Motion, Articular
PubMed: 37496207
DOI: 10.1093/bmb/ldad018 -
Cannabis and Cannabinoid Research Aug 2023This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for... (Review)
Review
This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for interventional human trials using cutaneously administered CBD or reported plasma CBD concentrations (any species). Eight of 544 articles fitted the selection criteria: 3 placebo-controlled randomized and 5 single-arm trials. Eleven more studies were found in clinical trial databases but not accessible. Symptoms targeted were dermatopathologies or safety (two studies), pain (two), and behavior (one). Doses were 50-250 mg or 0.075-1.0% CBD, but coformulated with other ingredients. Risk of bias was high and reporting deficiencies further compromised data reliability. Diverse methodologies and formulations hampered syntheses for CBD dose, efficacy, and safety. Plasma CBD levels in dogs and rodents were 0.01-5 μM translating to <100 nM free, unbound CBD in humans. Adverse events were uncommon and mild, but meaningless without CBD's contribution to efficacy data. Achievable CBD plasma concentrations ∼100 nM can interact predominantly with high-affinity CBD targets, for example, TRPA1 and TRPM8 membrane channels that are abundantly expressed in pathological conditions. Even if reached, higher CBD concentrations on less susceptible targets risk complex and unsafe CBD therapy. A conceptual framework is proposed where dermal capillary loops create sinking for topical CBD demonstrating parallels between topical and transdermal CBD administration. Users risk generalizing inadequately designed trials to all CBD preparations. New clinical trials are urgently needed: they must demonstrate that outcomes are solely from CBD pharmacology, are reliable, unbiased, safe, and comparable. Measurements of sustained plasma CBD levels are mandatory, irrespective of administration route for successful translation from systems that express human molecular targets. Placebos must be appropriate. Transcutaneous and topical formulations need preliminary studies to optimize CBD skin penetration. Then, users can rationally balance efficacy against potential harms and cost-effectiveness of CBD formulations.
Topics: Humans; Animals; Dogs; Cannabidiol; Reproducibility of Results; Pain; Administration, Cutaneous; Seizures
PubMed: 35605018
DOI: 10.1089/can.2021.0154 -
Retina (Philadelphia, Pa.) Sep 2014To review the ocular pharmacology and antitumor activity of topotecan for the treatment of retinoblastoma by an evaluation of different routes of administration. (Review)
Review
PURPOSE
To review the ocular pharmacology and antitumor activity of topotecan for the treatment of retinoblastoma by an evaluation of different routes of administration.
METHODS
Systematic review of studies available at PubMed using the keywords retinoblastoma, topotecan, and camptothecins, including preclinical data such as cell lines and animal models, as well as clinical studies in patients with retinoblastoma.
RESULTS
Forty-two available studies were reviewed. Evidence of antitumor activity against retinoblastoma as a single agent is based on data on cell lines and a limited number of affected patients with intraocular and extraocular disease when given in a protracted schedule. Evidence of additive or synergistic activity in combination with other agents such as carboplatin, melphalan, and vincristine was reported in preclinical and clinical models. In animal models, pharmacokinetic evaluation of topotecan administered by the periocular route shows that most of the drug reaches the vitreous through the systemic circulation. Topotecan administered by intravitreal injection shows high and sustained vitreal concentrations with limited systemic exposure and lack of retinal toxicity at a dose of up to 5 μg. Topotecan administered intraophthalmic artery shows higher passage to the vitreous compared with periocular administration in a swine model.
CONCLUSION
Topotecan alone or in combination is active against retinoblastoma. It shows a favorable passage to the vitreous when given intravenously and intraarterially, and ocular toxicity is minimal by all routes of administration. However, its clinical role, optimal dose, and route of administration for the treatment of retinoblastoma are to be determined.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Routes; Humans; Intravitreal Injections; Retinal Neoplasms; Retinoblastoma; Tissue Distribution; Topoisomerase I Inhibitors; Topotecan; Tumor Cells, Cultured; Vitreous Body
PubMed: 25099219
DOI: 10.1097/IAE.0000000000000253 -
European Journal of Clinical... May 2021Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from...
PURPOSE
Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from reality) and increases in systolic and diastolic blood pressure. The objective of this structured review was to examine the effect of ketamine formulation and route of administration on its pharmacokinetics, safety and tolerability, to identify formulation characteristics and routes of administration that might minimise side effects.
METHODS
This was a structured review of published ketamine pharmacokinetics, safety and tolerability data for any ketamine formulation. The ratio of ketamine:norketamine was calculated from reported C values, as a measure of first pass metabolism. The effect of formulation and route of administration on safety was evaluated by measuring mean changes in systolic blood pressure and tolerability by changes in dissociation ratings. Data were correlated using Spearman's method.
RESULTS
A total of 41 treatment arms were identified from 21 publications, and included formulation development studies in healthy volunteers, and studies in clinical populations (patients undergoing anaesthesia, or being treated for pain or depression). Ketamine:norketamine ratios were strongly positively correlated with change in dissociation ratings (r = 0.89) and change in blood pressure (r = 0.96), and strongly negatively correlated with ketamine T (r = - 0.87; p < 0.00001 for all). Ketamine T strongly positively correlated with a change in dissociation ratings (r = - 0.96) and change in blood pressure (r = - 0.99; p < 0.00001 for all).
CONCLUSION
Ketamine formulations that maximize first pass metabolism and delay T will be better tolerated and safer than formulations which lack those characteristics.
Topics: Antidepressive Agents; Dissociative Disorders; Drug Administration Routes; Drug Delivery Systems; Humans; Hypertension; Ketamine; Metabolic Clearance Rate
PubMed: 33210159
DOI: 10.1007/s00228-020-03047-z -
Current Drug Discovery Technologies 2022Turmeric (Curcuma longa L.) is a popular spice containing curcumin that is responsible for its therapeutic effects. Curcumin with anti-inflammatory, antioxidant,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Turmeric (Curcuma longa L.) is a popular spice containing curcumin that is responsible for its therapeutic effects. Curcumin with anti-inflammatory, antioxidant, anti-cancer, and antimicrobial activities has led to a lot of research focusing on it over the years. This systematic review aimed to evaluate research on the anti-Plasmodium berghei activity of curcumin and its derivatives.
METHODS
Our study was performed according to PRISMA guidelines and was recorded in the database of a systematic review and preclinical meta-analysis of CAMARADESNC3Rs (SyRF). The search was performed in five databases, namely Scopus, PubMed, Web of Science, EMBASE, and Google Scholar, from 2010 to 2020. The following keywords were searched: "Plasmodium berghei", "Medicinal Plants", "Curcumin", "Concentration", Animals kind", "Treatment Durations", "Routes of Administration" and "in vivo".
RESULTS
Of the 3,500 papers initially obtained, 14 articles were reliable and were thus scrutinized. Animal models were included in all studies. The most commonly used animal strain was Albino (43%), followed by C57BL/6 (22%). The other studies used various murine strains, including BALB/c (14%) and ICR (7%). Two (14%) studies did not mention the strain of animal model used. Curcumin alone or in combination with other compounds depending on the dose used, route of administration, and animal model showed a moderate to strong anti-Plasmodium berghei effect.
CONCLUSION
According to the studies, curcumin has anti-malarial effects on Plasmodium berghei, and, however, its effect on human Plasmodium is unclear. Due to the side effects and drug resistance of current drugs in the treatment of human malaria, the use of new compounds with few or no side effects, such as curcumin, is recommended as an alternative or complementary treatment.
Topics: Animals; Anti-Inflammatory Agents; Antimalarials; Curcumin; Malaria; Mice; Plasmodium berghei
PubMed: 35293297
DOI: 10.2174/1570163819666220315140736 -
Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis.Journal of Neurology Aug 2017Glucocorticoids are the standard of care for multiple sclerosis (MS) relapses, but the most desirable route of administration is still matter of debate. The aim of the... (Meta-Analysis)
Meta-Analysis Review
Glucocorticoids are the standard of care for multiple sclerosis (MS) relapses, but the most desirable route of administration is still matter of debate. The aim of the study was to compare the efficacy and safety of oral versus intravenous steroids for treatment of acute relapses in patients with MS. Randomized or quasi-randomized, parallel group trials with direct comparison between oral and intravenous steroid treatment in MS patients with acute relapse were identified through a systematic literature search. Six trials were included involving 419 participants, 210 for oral, and 209 for intravenous groups, respectively. The weighted mean differences (WMDs) in the Kurtzke's Expanded Disability Status Scale (EDSS) score reduction between the oral and intravenous groups were 0.32 [(-0.09 to 0.73); p = 0.129] and 0.11 [(-0.12 to 0.33); p = 0.355] at 1 and 4 weeks after treatment, respectively. The risk ratios (RRs) for improvement by at least one EDSS point were 0.79 [(0.37-1.68); p = 0.539] at week 1 and 0.92 (0.76-1.12); p = 0.400] at week 4. There were no differences in the relapse rate and relapse freedom at 6 months between groups. The WMDs in the mean percentage reduction of Gadolinium-enhancing lesions between oral and intravenous arms were 0.14 (-0.02, 0.29); p = 0.083] and 0.04 (-0.19, 0.28); p = 0.705] at 1 and 4 weeks from treatment. Among the adverse events, insomnia was significantly associated with the oral route of steroid administration [RR 1.25 (1.07-1.46); p = 0.005]. In adult patients with acute MS relapse, there were no clear-cut differences in the efficacy and overall tolerability between oral and intravenous steroids.
Topics: Administration, Intravenous; Administration, Oral; Glucocorticoids; Humans; Immunologic Factors; Multiple Sclerosis; Randomized Controlled Trials as Topic; Steroids
PubMed: 28492970
DOI: 10.1007/s00415-017-8505-0 -
Vaccine Feb 2021There are a myriad of vaccine schedules for rabies pre- (PrEP) and post-exposure prophylaxis (PEP) that differ in the number and timedoses, number of visits, length of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are a myriad of vaccine schedules for rabies pre- (PrEP) and post-exposure prophylaxis (PEP) that differ in the number and timedoses, number of visits, length of schedule, and route of administration. The objective of this study was to systematically review the evidence and investigate how thedifferences in schedules influence titres over time.
METHODS
Four databaseswere searched from inception to January 2020 for rabies PrEP and PEP studies. Adose-response meta-analysis was utilised to pool geometric mean titres (GMT) over time. Subgroup analyses by route of administration, age group, and schedule were conducted.
RESULTS
80 studies met the inclusion criteria and contributed with 191 datasets and 12,413 participants. Both intradermal (ID) and intramuscular (IM) PrEP/PEP produce adequate GMTs. Significantly lower GMT levels were achieved in older (>50yrs) compared to younger (<50yrs) participants. Short 1-week schedules were as effective as longer schedules that can take between 3 and 12 weeks to complete.
CONCLUSIONS
Several effective ID and IM schedules were identified, the selection of a schedule should take into account the patient's needs, costs, availability to return for subsequent doses, and the time required to complete the schedule. Older individuals warrant special attention as they develop lower antibody response.
Topics: Aged; Antibodies, Viral; Humans; Injections, Intradermal; Injections, Intramuscular; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Vaccination
PubMed: 33478786
DOI: 10.1016/j.vaccine.2021.01.023