The many forms of cannabis use: Prevalence and correlates of routes of administration among nationally representative samples of U.S. adult and adolescent cannabis users.

BACKGROUND: Cannabis legalization has made cannabis accessible via dispensaries which sell a wide variety of cannabis products. Importantly, the various routes of administration are associated with differing consequences. As such, it's crucial to understand the prevalence and correlates of different cannabis products. Unfortunately, research has yet to examine the prevalence of certain forms of cannabis use, and little is known about the prevalence of using multiple forms of cannabis, and whether individual-level factors are associated with using different forms of cannabis. METHODS: The current study uses data from the 2022 National Survey on Drug Use and Health (NSDUH) to examine the prevalence and correlates of eight different types of cannabis use (smoking, vaping, eating/drinking, dabbing, drops/lozenges, topical, pills, and other), as well as a cannabis variety scale, on samples of adult and adolescent cannabis users. RESULTS: The results suggest that certain routes of administration are more prevalent than others and that these patterns are fairly consistent between adults and adolescents. Similarly, for both adults and adolescents, the majority of users used more than one cannabis product. Lastly, several individual-level factors are associated with the various forms of cannabis use and many of these associations vary by the route of administration examined. CONCLUSIONS: The results of the current study demonstrate that there are differences among cannabis users. If we can develop an understanding of who uses the various forms of cannabis, we could identify the users of the more dangerous forms and provide these individuals with more resources.

Comparison of Routes of Administration, Frequency, and Duration of Favipiravir Treatment in Mouse and Guinea Pig Models of Ebola Virus Disease.

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013-2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.

Safely Doing Less Antibiotics: Evidence to Guide Duration and Route of Administration in Common Pediatric Infections.

The growing evidence detailing the harmful effects of exposure to antibiotics has driven an urgency to evaluate recommendations in common pediatric infections regarding antibiotic course duration and route of administration. The past decade has produced strong evidence in support of many patients with uncomplicated common pediatric infections receiving shortened antibiotic durations and early conversion from intravenous to oral antibiotics. In this review, we offer guidance to providers in selection of duration and route of administration in a subset of common pediatric infections, including community-acquired pneumonia, osteomyelitis, and infections of the head and neck. [Pediatr Ann. 2024;53(6):e229-e233.].

An Assessment of Administration Route on MSC-sEV Therapeutic Efficacy.

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.

Cannabidiol and its application in the treatment of oral diseases: therapeutic potentials, routes of administration and prospects.

Cannabidiol (CBD), one of the most important active ingredients in cannabis, has been reported to have some pharmacological effects such as antibacterial and analgesic effects, and to have therapeutic potential in the treatment of oral diseases such as oral cancer, gingivitis and periodontal diseases. However, there is a lack of relevant systematic research and reviews. Therefore, based on the etiology and clinical symptoms of several common oral diseases, this paper focuses on the therapeutic potential of CBD in periodontal diseases, pulp diseases, oral mucosal diseases, oral cancer and temporomandibular joint diseases. The pharmacological effects of CBD and the distribution and function of its receptors in the oral cavity are also summarized. In order to provide reference for future research and further clinical application of CBD, we also summarize several possible routes of administration and corresponding characteristics. Finally, the challenges faced while applying CBD clinically and possible solutions are discussed, and we also look to the future.

[ROUTES OF MEDICAL CANNABIS ADMINISTRATION- IS SMOKING THE PREFERRED ROUTE?]

INTRODUCTION: The number of medical cannabis licenses in Israel is increasing persistently (over 120,000 approved licenses in October 2022), reaching about 1.5% of adult population. Medical cannabis products are available in two main forms: inflorescence (administered by smoking or evaporation) and cannabis oil (administered sub-lingually). Data from the Israel ministry of health, regarding the split between these forms, show a major preference for inflorescence products over cannabis oils. This preference is increasing over time. This article reviews the main differences between the administration of these forms and their effects on the quality of treatment. It's conclusion is that for the most common cases of cannabis treatment, sublingual oils should be preferred and that the medical community has an important role in driving this change.

Cardiovascular and Respiratory Effects of Cannabis Use by Route of Administration: A Systematic Review.

Aim: Knowledge of the cardiovascular and respiratory effects of cannabis use by route of administration is unclear. This evidence is necessary to increase clinical and public health awareness given the recent trend in cannabis legalization, normalization, and surge in the availability and usage of various forms of cannabis products. Methods: Search was conducted in Web of Science, ProQuest, Psych INFO, Scopus, Embase, and Medline databases, and subsequently in the references of retrieved articles. Peer-reviewed articles published between 2009 and 2023, that reported on cardiovascular and respiratory effects of cannabis use by route of administration were included. Studies with no report of the route of administration and combined use of other illicit substances were excluded. The review was guided by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results: Of the 1873 articles retrieved, 42 met inclusion criteria encompassing six case reports, 21 reviews, and 15 empirical studies. Four administration routes were identified: smoking, vaping, oral ingestion, and dabbing. Smoking was the most common route of administration and was associated with both respiratory effects, such as bronchitis, dyspnea, and chronic obstructive lung disease, and cardiovascular effects including tachycardia, ventricular arrhythmias, and myocardial infarction. Cannabis edibles were associated with minimal respiratory effects. Tachycardia was the most common cardiovascular effect and was associated with all routes of administration. Conclusion: Cannabis use does cause cardiovascular and respiratory effects, but the conclusion remains tentative of the cardiovascular and respiratory effects by route of administration due to methodological limitations of the studies.

Exploring racial and secondary substance use differences in route of administration of opioid drugs: Analysis of the 2015-2019 treatment admission data.

INTRODUCTION: The opioid crisis continues to evolve with increasing opioid-related overdose deaths among under-represented minorities. A better understanding of substance use differences in the route of administration for people using heroin and other opioids can lead to targeted strategies and interventions. METHODS: Using the 2015-2019 Treatment Episode Data Set - Admissions (TEDS-A), a multinomial logistic regression model examined the relationship between race/ethnicity and secondary substance use with route of administration in a subset of 591,078 admissions. RESULTS: For individuals reporting heroin as their primary substance, minoritized clients were both more likely to smoke (NH Blacks RR: 2.28, 95 % CI 2.16-2.41; Hispanic RR: 1.80, 95 % CI: 1.74, 1.87; Other RR: 2.09, 95 % CI: 2.00, 2.20) or inhale heroin (Hispanic RR: 1.82, 95 % CI 1.78-1.85; Other RR: 1.30, 95 % CI 1.25, 1.34) compared to non-Hispanic (NH) Whites. NH Black clients were nearly seven and a half times more likely to report inhaling (RR: 7.45, 95 % CI 7.28, 7.62) heroin over injecting it. Clients were more likely to smoke heroin compared to injection if they reported secondary drug use of methamphetamines (RR: 2.28, 95 % CI 2.21, 2.35) and other opioids (RR: 1.21, 95 % CI 1.15, 1.28). For clients reporting other opioids as their primary substance, Hispanic (RR: 1.33, 95 % CI 1.19, 1.47) and other racial/ethnic minority clients (RR: 2.50, 95 % CI 2.23, 2.79) were more likely to smoke opioids vs take it orally compared to their NH White counterparts. Individuals who reported methamphetamine use as a secondary substance were significantly more than three times as likely to smoke (RR: 3.07, 95 % CI 2.74, 3.45) or inject (RR: 3.36, 95 % CI 3.17, 3.57) compared to orally ingesting opioids, while those who reported cocaine or crack cocaine use were more than twice as likely to inject (RR: 2.22, 95 % CI 2.09-2.36) opioids than taking them orally. CONCLUSION: Findings demonstrate significant racial and ethnic differences in the route of administration. This work expands on the understanding of the complex nature of polysubstance use in the evolving opioid crisis and the secondary substance use of clients on routes of administration of opioids and heroin, highlighting the need for tailored interventions to address the treatment needs of under-represented minorities.

Long-Acting Strategies for Antibody Drugs: Structural Modification, Controlling Release, and Changing the Administration Route.

Because of their high specificity, high affinity, and targeting, antibody drugs have been widely used in the treatment of many diseases and have become the most favored new drugs for research in the world. However, some antibody drugs (such as small-molecule antibody fragments) have a short half-life and need to be administered frequently, and are often associated with injection-site reactions and local toxicities during use. Increasing attention has been paid to the development of antibody drugs that are long-acting and have fewer side effects. This paper reviews existing strategies to achieve long-acting antibody drugs, including modification of the drug structure, the application of drug delivery systems, and changing their administration route. Among these, microspheres have been studied extensively regarding their excellent tolerance at the injection site, controllable loading and release of drugs, and good material safety. Subcutaneous injection is favored by most patients because it can be quickly self-administered. Subcutaneous injection of microspheres is expected to become the focus of developing long-lasting antibody drug strategies in the near future.

Efficacy of different routes of acetaminophen administration for postoperative pain in children: a systematic review and network meta-analysis.

PURPOSE: Acetaminophen is the most common drug used to treat acute pain in the pediatric population, given its wide safety margin, low cost, and multiple routes for administration. We sought to determine the most efficacious route of acetaminophen administration for postoperative acute pain relief in the pediatric surgical population. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) that included children aged between 30 days and 17 yr who underwent any type of surgical procedure and that evaluated the analgesic efficacy of different routes of administration of acetaminophen for the treatment of postoperative pain. We searched MEDLINE, CENTRAL, Embase, CINAHL, LILACs, and Google Scholar databases for trials published from inception to 16 April 2023. We assessed the risk of bias in the included studies using the Cochrane Risk of Bias 1.0 tool. We performed a frequentist network meta-analysis using a random-effects model. Our primary outcome was postoperative pain using validated pain scales. RESULTS: We screened 2,344 studies and included 14 trials with 829 participants in the analysis. We conducted a network meta-analysis for the period from zero to two hours, including six trials with 496 participants. There was no evidence of differences between intravenous vs rectal routes of administration of acetaminophen (difference in means, -0.28; 95% confidence interval [CI], -0.62 to 0.06; very low certainty of the evidence) and intravenous vs oral acetaminophen (difference in means, -0.60; 95% CI, -1.20 to 0.01; low certainty of the evidence). For the comparison of oral vs rectal routes, we found evidence favouring the oral route (difference in means, -0.88; 95% CI, -1.44 to -0.31; low certainty of the evidence). Few trials reported secondary outcomes of interest; when comparing the oral and rectal routes in the incidence of nausea and vomiting, there was no evidence of differences (relative risk, 1.20; 95% CI, 0.81 to 1.78). CONCLUSION: The available evidence on the effect of the administration route of acetaminophen on postoperative pain in children is very uncertain. The outcomes of postoperative pain control and postoperative vomiting may differ very little between the oral and rectal route. Better designed and executed RCTs are required to address this important clinical question. STUDY REGISTRATION: PROSPERO (CRD42021286495); first submitted 19 November 2021.

RéSUMé: OBJECTIF: Compte tenu de sa large marge de sécurité, de son faible coût et de ses multiples voies d'administration, l'acétaminophène est le médicament le plus couramment utilisé pour traiter la douleur aiguë dans la population pédiatrique. Nous avons cherché à déterminer la voie d'administration d'acétaminophène la plus efficace pour le soulagement de la douleur aiguë postopératoire dans la population chirurgicale pédiatrique. MéTHODE: Nous avons réalisé une revue systématique d'études randomisées contrôlées (ERC) qui ont inclus des enfants âgé·es de 30 jours à 17 ans ayant bénéficié de n'importe quel type d'intervention chirurgicale et qui ont évalué l'efficacité analgésique de différentes voies d'administration d'acétaminophène pour le traitement de la douleur postopératoire. Nous avons mené des recherches dans les bases de données MEDLINE, CENTRAL, Embase, CINAHL, LILAC et Google Scholar pour en tirer les études publiées depuis leur création jusqu'au 16 avril 2023. Le risque de biais dans les études incluses a été évalué à l'aide de l'outil de Risque de biais 1.0 de Cochrane. Nous avons réalisé une méta-analyse de réseau fréquentiste à l'aide d'un modèle à effets aléatoires. Notre critère d'évaluation principal était la douleur postopératoire mesurée à l'aide d'échelles de douleur validées. RéSULTATS: Nous avons passé en revue 2344 études et inclus 14 études incluant un total de 829 enfants dans l'analyse. Nous avons mené une méta-analyse en réseau pour une période allant de zéro à deux heures, comprenant six études avec 496 participant·es. Il n'y avait aucune preuve de différences entre les voies d'administraion intraveineuse vs rectale de l'acétaminophène (différence de moyennes, −0,28; intervalle de confiance [IC] à 95 %, −0,62 à 0,06; très faible certitude des données probantes) et entre les voies intraveineuse vs orale (différence de moyennes, −0,60; IC 95 %, −1,20 à 0,01; faible certitude des données probantes). Pour la comparaison des voies orale vs rectale, nous avons trouvé des données probantes en faveur de la voie orale (différence de moyennes, −0,88; IC 95 %, −1,44 à −0,31; faible degré de certitude des données probantes). Peu d'études ont rapporté des résultats secondaires d'intérêt; en comparant les voies orale et rectale dans l'incidence des nausées et des vomissements, il n'y avait aucune preuve de différences (risque relatif, 1,20; IC 95 %, 0,81 à 1,78). CONCLUSION: Les données probantes disponibles sur l'effet de la voie d'administration de l'acétaminophène sur la douleur postopératoire chez les enfants sont très incertaines. Les résultats de contrôle de la douleur postopératoire et de vomissements postopératoires peuvent différer très peu entre la voie orale et la voie rectale. Des ERC mieux conçues et mieux exécutées sont nécessaires pour répondre à cette importante question clinique. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021286495); première soumission le 19 novembre 2021.

Challenges and Therapeutic Approaches for the Protein Delivery System: A Review.

The protein delivery system is one of the innovative or novel drug delivery systems in the present era. Proteins play an indispensable role in our body and are mainly found in every part, like tissue and cells of our body. It also controls various functions, such as maintaining our tissue, transportation, muscle recovery, enzyme production and acting as an energy source for our body. Protein therapeutics have big future perspectives, and their use in the treatment of a wide range of serious diseases has transformed the delivery system in the pharmaceutical and biotechnology industries. The chief advantage of protein delivery is that it can be delivered directly to the systemic circulation. So far, parenteral routes, such as intravenous, intramuscular, and subcutaneous, are the most often used method of administering protein drugs. Alternative routes like buccal, oral, pulmonary, transdermal, nasal, and ocular routes have also shown a remarkable success rate. However, as with all other types of delivery, here, several challenges are posed due to the presence of various barriers, such as the enzymatic barrier, intestinal epithelial barrier, capillary endothelial barrier, and blood-brain barrier. There are several approaches that have been explored to overcome these barriers, such as chemical modification, enzymatic inhibitors, penetration enhancers, and mucoadhesive polymers. This review article discusses the protein, its functions, routes of administration, challenges, and strategies to achieve ultimate formulation goals. Recent advancements like the protein Pegylation method and Depofoam technology are another highlight of the article.

Cannabidiol for the Treatment of Brain Disorders: Therapeutic Potential and Routes of Administration.

The use of cannabidiol (CBD) for treating brain disorders has gained increasing interest. While the mechanism of action of CBD in these conditions is still under investigation, CBD has been shown to affect numerous different drug targets in the brain that are involved in brain disorders. Here we review the preclinical and clinical evidence on the potential therapeutic use of CBD in treating various brain disorders. Moreover, we also examine various drug delivery approaches that have been applied to CBD. Due to the slow absorption and low bioavailability with the current oral CBD therapy, more efficient routes of administration to bypass hepatic metabolism, particularly pulmonary delivery, should be considered. Comparison of pharmacokinetic studies of different delivery routes highlight the advantages of intranasal and inhalation drug delivery over other routes of administration (oral, injection, sublingual, buccal, and transdermal) for treating brain disorders. These two routes of delivery, being non-invasive and able to achieve fast absorption and increase bioavailability, are attracting increasing interest for CBD applications, with more research and development expected in the near future.

Patient Preferences for Benefits, Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes.

INTRODUCTION/BACKGROUND: Therapy with infused or injected hypomethylating agents (HMAs) may lead to higher treatment administration burden (ie, local reaction, visit frequency and duration) vs. oral HMAs.   OBJECTIVES: To reveal preferences of US and Canadian patients with myelodysplastic syndromes (MDS) for HMAs' benefits, risks, and administration burden through an online discrete-choice experiment (DCE). MATERIALS AND METHODS: Choice of DCE attributes and survey development were informed by literature review and interviews with clinicians, MDS patients, and caregivers serving as patient proxies, and patient advocacy groups (PAGs) representatives, including from AAMAC, AAMDS, and MDSF. DCE choice tasks were analyzed using random parameter logit models. Survey patients were recruited by the PAGs via their networks. To understand key preference drivers and how much patients were willing to trade between attributes, we calculated each attribute's relative attribute importance (RAI) and marginal rates of substitution. RESULTS: One hundred eighty-four respondents (including 158 patients; mean age, 67.2 years; male, 50.5%; White, 50.5%; US residents, 88%) completed the survey. MDS risk was low (34.8%), high (30.9%), or unknown (34.2%). RAI (in decreasing order) was as follows: risk of AML (40%), fatigue level (33%), number of visits (12%), mode of administration (6%), visit duration (5%), and administration frequency (4%). Assuming the same risk of AML transformation or level of fatigue, most respondents (76.6%) were predicted to switch to an oral pill if it were available to them. CONCLUSION: Given equivalent effectiveness across HMAs, patients' preferences for HMA administration method should be considered in treatment decision-making to minimize burden and facilitate adherence.

Women's preferences and acceptance for different drug delivery routes and products.

To use or not to use, that is the first decision to take regarding a drug product. This mandatory step for adherence dictates product efficacy. The determinants for such decision do not only rely on the priority of the therapeutic or preventive strategy, but are related to a complex network of perceptions, preferences, personal and cultural backgrounds, and results from previous experiences. Women's preferences for dosage forms and even for drug delivery routes have been mainly studied in the fields of contraception and HIV prevention (and their related multipurpose approaches). Much less attention has been devoted to other therapeutic or preventive strategies. In a time when patient-centred approaches and shared decisions are increasingly valued, considering women's preferences and their main determinants is essential for product development and selection. Such products will be more likely to be chosen and used as intended, increasing efficacy, and reducing the overall costs related with these treatments. This knowledge shall be integrated in early stages of product development. This article reviews the state of the art related with women's preferences and acceptance for different dosage forms and drug delivery routes involved in women's health. The methodologies used for collecting these data and their major drawbacks are discussed. Results obtained from acceptability studies and the main determinants for selection of preventive and treatment drug products are discussed as tools for new developments in the field.

Ovarian response to intraovarian platelet-rich plasma (PRP) administration: hypotheses and potential mechanisms of action.

PURPOSE: Platelet-rich plasma (PRP) therapy has been used as an adjunct to fertility treatments in women with very low ovarian reserve and premature ovarian insufficiency. Recent literature in both humans and animals suggest that intraovarian PRP administration in the setting of poor ovarian reserve may help ovarian function and increase the chances of pregnancy. METHODS: A comprehensive literature search through PubMed, MEDLINE databases, and recent abstracts published at relevant society meetings was performed and resulted in 25 articles and 2 abstracts published that studied effect of PRP on the ovaries for the purpose of reproduction. RESULTS: This review article presents all the data published to date pertaining to intraovarian PRP injection and pregnancy, both naturally and after in vitro fertilization. It also presents the most recent data on the use of ovarian PRP in in vitro and animal model studies highlighting the possible mechanisms by which PRP could impact ovarian function. CONCLUSIONS: Even though recent commentaries questioned the use of PRP as an "add-on" therapy in fertility treatment because it has not been thoroughly studied, the recent basic science studies presented here could increase awareness for considering more serious research into the efficacy of PRP as an adjunct for women with poor ovarian reserve, premature ovarian insufficiency, and even early menopause who are trying to conceive using their own oocytes. Given its low-risk profile, the hypothetical benefit of PRP treatment needs to be studied with larger randomized controlled trials.

Alternative Routes of Administration of Clozapine.

Clozapine is the only antipsychotic with proven effectiveness in treatment-resistant schizophrenia. It is usually administered using commercially available oral tablets, but not all patients are willing or able to take medicines in this way. Orodispersible clozapine tablets are available from several manufacturers and may be useful where swallowing solid dosage forms is difficult, or as an aid to observe compliance. Liquid formulations of clozapine can be prepared extemporaneously or purchased commercially, but most preparations are suspensions (clozapine is poorly soluble) and patients may find them unpalatable. The administration of clozapine (suspension or crushed tablets) via enteral feeding tubes (predominantly nasogastric) has been reported both in medically unwell patients and in patients refusing clozapine. Enteral administration is likely to be superseded by intramuscular clozapine, which has recently been re-introduced and is being widely used in some countries. Successful use of this formulation in enforced treatment strategies has been described by several authors with good long-term outcomes when switched to oral treatment. Intramuscular clozapine has also been used in physically ill patients who are unable to take any form of enteral medication. Other methods of delivery (transdermal, nasal) are not yet commercially available, but offer promise of further treatment options for this group of seriously ill patients.

Isobolographic analysis of antinociceptive effect of ketorolac, indomethacin, and paracetamol after simultaneous peripheral local and systemic administration.

This study was designed to characterize the type of interaction (subadditive, additive, or synergistic) after simultaneous administration by two different routes (intraperitoneal plus peripheral local) of the same nonsteroidal anti-inflammatory drugs (NSAID) ketorolac and indomethacin or paracetamol. The antinociceptive effects of locally or intraperitoneally delivery of NSAIDs or paracetamol, and the simultaneous administration by the two routes at fixed-dose ratio combination were evaluated using the formalin test. Pain-related behavior was quantified as the number of flinches of the injected paw. Isobolographic analysis was used to characterize the interaction between the two routes. ED30 values were estimated for individual drugs, and isobolograms were constructed. Ketorolac, indomethacin, or paracetamol and fixed-dose ratio combinations produced a dose-dependent antinociceptive effect in the second but not in the first phase of the formalin test. The analysis of interaction type after simultaneous administration by the two routes the same NSAID or paracetamol (on basis of their ED30), revealed that the simultaneous administration of ketorolac or paracetamol was additive and for indomethacin was synergistic. Since the mechanisms underlying the additive effect of ketorolac or paracetamol and the synergistic effect of indomethacin were not explored; it is possible that the peripheral and central mechanism is occurring at several anatomical sites. The significance of these findings for theory and pain pharmacotherapy practice indicates that the combination of one analgesic drug given simultaneously by two different administration routes could be an additive or it could lead to a synergistic interaction.

The Regenerative Potential of Substance P.

Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still a great challenge for medicine. For many years, research has been carried out on finding new therapeutics which improve the healing of chronic wounds. One of the most extensively studied active substances that has been widely tested in the treatment of different types of wounds was Substance P (SP). SP is one of the main neuropeptides released by nervous fibers in responses to injury. This review provides a thorough overview of the application of SP in different types of wound models and assesses its efficacy in wound healing.

FDA Warns Against Using Needle-Free Injection Devices For Dermal Fillers.

The Food and Drug Administration (FDA) has issued a safety communication to warn the public and health care professionals not to use needle-free devices for injection of dermal fillers. These devices are not approved by the FDA. FDA-approved dermal fillers are for prescription use only with a syringe and either a needle or cannula.Nurses should inform patients not to purchase any needle-free devices or products over the internet. Adverse effects from these devices should be reported to the FDA's MedWatch system.

Dodging blood brain barrier with "nano" warriors: Novel strategy against ischemic stroke.

Ischemic stroke (IS) is one of the leading causes of death and disability resulting in inevitable burden globally. Ischemic injury initiates cascade of pathological events comprising energy dwindling, failure of ionic gradients, failure of blood brain barrier (BBB), vasogenic edema, calcium over accumulation, excitotoxicity, increased oxidative stress, mitochondrial dysfunction, inflammation and eventually cell death. In spite of such complexity of the disease, the only treatment approved by US Food and Drug Administration (FDA) is tissue plasminogen activator (t-PA). This therapy overcome blood deficiency in the brain along with side effects of reperfusion which are responsible for considerable tissue injury. Therefore, there is urgent need of novel therapeutic perspectives that can protect the integrity of BBB and salvageable brain tissue. Advancement in nanomedicine is empowering new approaches that are potent to improve the understanding and treatment of the IS. Herein, we focus nanomaterial mediated drug delivery systems (DDSs) and their role to bypass and cross BBB especially via intranasal drug delivery. The various nanocarriers used in DDSs are also discussed. In a nut shell, the objective is to provide an overview of use of nanomedicine in the diagnosis and treatment of IS to facilitate the research from benchtop to bedside.