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[Display omitted] • This review provides a systematic summary of FDA-approved biologic-device combination products regarding their device configurations, routes of administration, formulations, instructions for use, etc. • While prefilled syringes, autoinjectors and pen injectors remain as the mainstay of medical devices, innovative modifications like dual-chamber design and novel devices like on-body injector also emerged as promising presentations. • Insulin related combination products are all delivered by pen injectors with multi-dose cartridges subcutaneously. Vaccine-device combination products are presented with PFS and administered through the intramuscular route. • Around 40 % of products employ high-concentration formulations (≥ 100 mg/mL), and 78 % of mAb products are at high concentrations. With the remarkably strong growth of the biopharmaceutical market, an increasing demand for self-administration and rising competitions attract substantial interest to the biologic-device combination products. The ease-of-use of biologic-device combination products can minimize dosing error, improve patient compliance and add value to the life-cycle management of biological products. As listed in the purple book issued by the U.S. Food and Drug Administration (FDA), a total of 98 brand biologic-device combination products have been approved with Biologic License Application from January 2000 to August 2023, where this review mainly focused on 63 products containing neither insulin nor vaccine. Prefilled syringes (PFS) and autoinjectors are the most widely adopted devices, whereas innovative modifications like needle safety guard and dual-chamber design and novel devices like on-body injector also emerged as promising presentations. All 16 insulin products employ pen injectors, while all 19 vaccine products are delivered by a PFS. This review provides a systematic summary of FDA-approved biologic-device combination products regarding their device configurations, routes of administration, formulations, instructions for use, etc. In addition, challenges and opportunities associated with biologic-device compatibility, regulatory complexity, and smart connected devices are also discussed. It is believed that evolving technologies will definitely move the boundaries of biologic-device combination product development even further. [ABSTRACT FROM AUTHOR]

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.

Hydrogels are hydrophilic, three-dimensional, cross-linked polymers that absorb significant amounts of biological fluids or water. Hydrogels possess several favorable properties, including flexibility, stimulus-responsiveness, versatility, and structural composition. They can be categorized according to their sources, synthesis route, response to stimulus, and application. Controlling the cross-link density matrix and the hydrogels' attraction to water while they're swelling makes it easy to change their porous structure, which makes them ideal for drug delivery. Hydrogel in drug delivery can be achieved by various routes involving injectable, oral, buccal, vaginal, ocular, and transdermal administration routes. The hydrogel market is expected to grow from its 2019 valuation of USD 22.1 billion to USD 31.4 billion by 2027. Commercial hydrogels are helpful for various drug delivery applications, such as transdermal patches with controlled release characteristics, stimuli-responsive hydrogels for oral administration, and localized delivery via parenteral means. Here, we are mainly focused on the commercial hydrogel products used for drug delivery based on the described route of administration. [ABSTRACT FROM AUTHOR]

Background: Dosage forms (DF), which are primarily divided into solid, semisolid, liquid, and gaseous, are among the different factors that influence drug adherence. Thus, the purpose of this study was to evaluate how patients' preferences for pharmaceutical DF affected their adherence to medication in community pharmacies in Gondar town. Methods: A cross-sectional study on community pharmacies was carried out from June 25 to July 27, 2023. The statistical package for social sciences, version 26, was used for data analysis. Factors associated with patient medication discontinuation were found using both bivariate and multivariate logistic regressions. Results: According to our study, the majority of respondents (42.4%) preferred tablet DF. Most respondents (63.9%) DF preference was affected by the size of the medication, in which small-sized were most preferable (59.6%). The oral route of administration was the most preferable (71.2%). The majority of the respondents (59.9%) had a history of discontinuation of medicines. Being male (AOR=2.21, 95% CI: 1.29, 3.79), living in rural areas (AOR=1.98, 95% CI: 1.03, 3.83), types of DF (AOR=4.59, 95% CI: 1.28, 16.52), high frequency of administration (AOR=2.22, 95% CI: 1.08, 4.57), high cost of medication (AOR=3.09, 95% CI: 1.69, 5.68), getting some improvement from illness (AOR=3.29, 95% CI: 1.10, 9.87), and high number of drugs (AOR=3.29, 95% CI: 1.67, 13.85) were significantly associated with medication discontinuation. Conclusion: Our findings showed that tablet dosage forms, oral routes of administration, and once-daily taking of medicines were the most preferred by our respondents. Being male, living in rural areas, types of DF, high frequency of administration, high cost of medication, getting some improvement from illness, and high number of drugs were significantly associated with medication discontinuation. This provides an insight into what to consider when prescribing medicine to enhance patients' adherence and overall therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Hydrogels are hydrophilic, three-dimensional, cross-linked polymers that absorb significant amounts of biological fluids or water. Hydrogels possess several favorable properties, including flexibility, stimulus-responsiveness, versatility, and structural composition. They can be categorized according to their sources, synthesis route, response to stimulus, and application. Controlling the cross-link density matrix and the hydrogels’ attraction to water while they’re swelling makes it easy to change their porous structure, which makes them ideal for drug delivery. Hydrogel in drug delivery can be achieved by various routes involving injectable, oral, buccal, vaginal, ocular, and transdermal administration routes. The hydrogel market is expected to grow from its 2019 valuation of USD 22.1 billion to USD 31.4 billion by 2027. Commercial hydrogels are helpful for various drug delivery applications, such as transdermal patches with controlled release characteristics, stimuli-responsive hydrogels for oral administration, and localized delivery via parenteral means. Here, we are mainly focused on the commercial hydrogel products used for drug delivery based on the described route of administration.

With the rapid development of gene therapy technology and the outbreak of coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) therapeutics have attracted more and more attention, and the COVID-19 mRNA vaccine has been approved by the Food and Drug Administration (FDA) for emergency authorization. To improve the delivery efficiency of mRNA in vitro and in vivo, researchers have developed a variety of mRNA carriers and explored different administration routes. This review will systematically introduce the types of mRNA vectors, routes of administration, storage methods, safety of mRNA therapeutics, and the type of diseases that mRNA drugs are applied for. Finally, some suggestions are supplied on the development direction of mRNA therapeutic agents in the future.

Background: Due to the interruption of the EHC pathway in NAFLD patients, we hypothesized that parenteral vitamin D supplementation is superior to oral in vitamin D insufficient patients with NAFLD. Therefore, this study aimed to compare the efficacy of oral and parenteral routes of vitamin D supplementation on serum 25(OH) vitamin D levels in patients with NAFLD. Methods: In this prospective randomized trial, 66 NAFLD cases with vitamin D deficiency were studied. For 33 cases, oral vitamin D was supplemented, whereas the other 33 patients were given an intramuscular injection of vitamin D. Laboratory tests and liver ultrasound were performed at the beginning and the end of the trial for each subject. Results: Regardless of the drug administration route, at the end of this trial the mean of serum 25-hydroxy vitamin D level increased from 8.74±2.47 to 33.16±17.61 (P=0.00), and the mean±SD for serum triglyceride decreased from 191.46±92.79 to 166.00±68.30 (P=0.02), both were statistically significant. Liver ultrasound reported statistically significant changes in the grade of fatty liver disease (P=0.003). In the comparison between the two groups, serum 25-hydroxy vitamin D level changes were not statistically significant (P=0.788). Conclusion: The intramuscular method of supplementation was not better than the oral route in improving serum 25(OH) vitamin D levels in NAFLD patients. In this study, the impaired EHC and vitamin D absorption inhibitor factors in NAFLD patients did not affect the final result of serum vitamin D levels significantly.

Abstract Background The wide heterogeneity of available cannabis products makes it difficult for physicians to appropriately guide patients. In the current study, our objective was to characterize naturalistic cannabis use routines and explore associations between routines and reported benefits from consuming cannabis. Methods We performed a mixed methods analysis of n=1087 cross-sectional survey responses from adults with self-reported chronic pain using cannabis for symptom management in the USA and Canada. First, we qualitatively analyzed responses to an open-ended question that assessed typical cannabis use routines, including administration routes, cannabinoid content, and timing. We then sub-grouped responses into categories based on inhalation (smoking, vaporizing) vs. non-inhalation (e.g., edibles). Finally, we investigated subgroups perceptions of how cannabis affected pain, overall health, and use of medications (e.g., substituting for opioids, benzodiazepines). Substitutions were treated as a count of medication classes, while responses for both pain and health were analyzed continuously, with − 2 indicating health declining a lot or pain increasing a lot and 2 indicating that health improved a lot or pain decreased a lot. Results Routines varied widely in terms of administration routes, cannabinoid content, and use timing. Overall, 18.8%, 36.2%, and 45% used non-inhalation, inhalation, and non-inhalation + inhalation routes, respectively. Those who used inhalation routes were younger (mean age 46.5 [inhalation] and 49.2 [non-inhalation + inhalation] vs. 56.3 [inhalation], F=36.1, p

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. [Display omitted] • The functional receptors of CBD and their distribution in oral cavity are briefly reviewed. • The potentials of CBD in the treatment of several oral diseases are summarized. • The administration routes of CBD are introduced to provide reference for the treatment of oral diseases. • The challenges, related solutions and prospects of clinically applying CBD are discussed. [ABSTRACT FROM AUTHOR]

Pain management in palliative care is both an art and a science. Essential to good pain control is an understanding not only of the pathophysiology of the origin of the pain, but also the impact that the pain is having, as the palliative patient may have to live with the symptoms of disease for months or even years. Interventions can then be targeted and at various times, may include a range of pharmacological treatments, psychological or spiritual support and possibly the involvement of other specialties to alleviate a particular problem. [ABSTRACT FROM AUTHOR]

Context: Luteal phase support (LPS) has become an essential component of IVF protocols following both fresh and frozen embryo transfers, yet there is still controversy with regards to the optimal protocol of LPS to enhance treatment outcome. Search strategy: A search via PubMed for all the selected topics was limited to publications from the past 10 years and to English language. We subsequently searched the reference lists of retrieved articles. Where available, RCTs were chosen over non-randomized studies. Here we provide an updated review of the current literature on various issues relating to LPS, in both fresh and frozen embryo transfers. The timing of LPS initiation as well as the route of administration and dosing are discussed for both fresh and frozen transfers. A separate discussion for frozen thawed embryo transfer in natural cycles and non-ovulatory cycles is presented. Conclusions: We present data that supports the use of Progesterone LPS in fresh and frozen embryo transfers. No benefits were found to the addition of hCG or estradiol to progesterone LPS in fresh transfers, however GnRH agonist may have a role. IM Progesterone was not advantageous over vaginal progesterone in fresh transfers but was superior in frozen transfers. The timing of LPS introduction, the interval to embryo transfer, as well as the serum concentration of progesterone, have significant effects on the success of the treatment. [ABSTRACT FROM AUTHOR]

Drug delivery to the anterior or posterior segments of the eye is a major challenge due to the protection barriers and removal mechanisms associated with the unique anatomical and physiological nature of the ocular system. The paper presents the preparation and characterization of drug-loaded polymeric particulated systems based on pre-emulsion coated with biodegradable polymers. Low molecular weight biopolymers (chitosan, sodium hyaluronate and heparin sodium) were selected due to their ability to attach polymer chains to the surface of the growing system. The particulated systems with dimensions of 190–270 nm and a zeta potential varying from −37 mV to +24 mV depending on the biopolymer charges have been obtained. Current studies show that particles release drugs (dexamethasone/pilocarpine/bevacizumab) in a safe and effective manner, maintaining therapeutic concentration for a longer period of time. An extensive modeling study was performed in order to evaluate the drug release profile from the prepared systems. In a multifractal paradigm of motion, nonlinear behaviors of a drug delivery system are analyzed in the fractal theory of motion, in order to correlate the drug structure with polymer. Then, the functionality of a SL(2R) type "hidden symmetry" implies, through a Riccati type gauge, different "synchronization modes" (period doubling, damped oscillations, quasi-periodicity and intermittency) during the drug release process. Among these, a special mode of Kink type, better reflects the empirical data. The fractal study indicated more complex interactions between the angiogenesis inhibitor Bevacizumab and polymeric structure. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

ContextLuteal phase support (LPS) has become an essential component of IVF protocols following both fresh and frozen embryo transfers, yet there is still controversy with regards to the optimal protocol of LPS to enhance treatment outcome.Search strategyA search via PubMed for all the selected topics was limited to publications from the past 10 years and to English language. We subsequently searched the reference lists of retrieved articles. Where available, RCTs were chosen over non-randomized studies. Here we provide an updated review of the current literature on various issues relating to LPS, in both fresh and frozen embryo transfers. The timing of LPS initiation as well as the route of administration and dosing are discussed for both fresh and frozen transfers. A separate discussion for frozen thawed embryo transfer in natural cycles and non-ovulatory cycles is presented.ConclusionsWe present data that supports the use of Progesterone LPS in fresh and frozen embryo transfers. No benefits were found to the addition of hCG or estradiol to progesterone LPS in fresh transfers, however GnRH agonist may have a role. IM Progesterone was not advantageous over vaginal progesterone in fresh transfers but was superior in frozen transfers. The timing of LPS introduction, the interval to embryo transfer, as well as the serum concentration of progesterone, have significant effects on the success of the treatment.

Gold nanorods (GNRs) show promising biomedical therapeutic/imaging applications. This study investigated the effect of PEGylated-GNRs on the angiogenesis factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) and their regulator (miR-29a-3p) under variable administration conditions--dosage, gender, routes of administration, and post-treatment intervals. In CD-1 mice of both genders, PEG-GNRs (94, 375, 750, and 1500 ng/kg body weight, ~40 nm, aspect ratio ~4.5) were injected via different routes: intravenous, subcutaneous, and intramuscular, and then VEGF and PDGF were estimated in sera by ELISA, after post-treatment intervals (1, 3, and 7 days). Low doses of PEG-GNRs (94 and 375 ng/kg body weight) resulted in antiangiogenic effects, while the highest dose (1500 ng/kg body weight) provoked a pro-angiogenic effect, especially in females and with intravenous route. The expression of miR-29a was significantly diminished in intravenous (IV) and intramuscular (IM) groups at day 7, in both males and females. miR-29a may be responsible for the increased VEGF in the highest PEGGNRs dose, but it is not responsible for the inhibited VEGF and PDGF levels in low PEG-GNRs doses. The study recommends the consideration of the critical role of dose, gender, and route of administration in PEG-GNRs pro-angiogenic activity, in medical applications as a direct cancer therapy and as a drug delivery agent. [ABSTRACT FROM AUTHOR]

Nanotechnology is currently a field of endeavour that has reached a maturation phase beyond the initial hypotheses with an undercurrent challenge to optimise the safety, and scalability for production and clinical trials. Lipid-based nanoparticles (LNP), namely solid lipid nanoparticles (SLN) and nanostructured lipid (NLC), carriers are presently among the most attractive and fastgrowing areas of research. SLN and NLC are safe, biocompatible nanotechnology-enabled platforms with ubiquitous applications. This review presents a modern vision that starts with a brief description of characteristics, preparation strategies, and composition ingredients, benefits, and limitations. Next, a discussion of applications and functionalization approaches for the delivery of therapeutics via different routes of delivery. Additionally, the review presents a concise perspective into limitations and future advances. A brief recap on the prospects of molecular dynamics simulations in better understanding NP bio-interface interactions is provided. Finally, the alliance between 3D printing and nanomaterials is presented here as well. [ABSTRACT FROM AUTHOR]

Background: Due to the interruption of the EHC pathway in NAFLD patients, we hypothesized that parenteral vitamin D supplementation is superior to oral in vitamin D insufficient patients with NAFLD. Therefore, this study aimed to compare the efficacy of oral and parenteral routes of vitamin D supplementation on serum 25(OH) vitamin D levels in patients with NAFLD. Methods: In this prospective randomized trial, 66 NAFLD cases with vitamin D deficiency were studied. For 33 cases, oral vitamin D was supplemented, whereas the other 33 patients were given an intramuscular injection of vitamin D. Laboratory tests and liver ultrasound were performed at the beginning and the end of the trial for each subject. Results: Regardless of the drug administration route, at the end of this trial the mean of serum 25-hydroxy vitamin D level increased from 8.74±2.47 to 33.16±17.61 (P=0.00), and the mean±SD for serum triglyceride decreased from 191.46±92.79 to 166.00±68.30 (P=0.02), both were statistically significant. Liver ultrasound reported statistically significant changes in the grade of fatty liver disease (P=0.003). In the comparison between the two groups, serum 25-hydroxy vitamin D level changes were not statistically significant (P=0.788). Conclusion: The intramuscular method of supplementation was not better than the oral route in improving serum 25(OH) vitamin D levels in NAFLD patients. In this study, the impaired EHC and vitamin D absorption inhibitor factors in NAFLD patients did not affect the final result of serum vitamin D levels significantly. [ABSTRACT FROM AUTHOR]

In the present study, we evaluated the effects of administering Enterococcus faecium in food and/or water on the hematological and immunological parameters, intestinal microbiota, resistance to bacterial diseases (streptococcosis and francisellosis) and growth of Nile tilapia. Before the in vivo experiment, probiotic bacteria isolated from Nile tilapia were selected via inhibition tests. Sequencing, annotation, and assembly of the complete genome of the selected bacteria as well as other tests were performed using bioinformatics tools. Three treatments were implemented: G1 (probiotic feeding), G2 (probiotic in water), and G3 (probiotic in food and water); and a negative control (NC) was also employed. Treatment lasted 38 days, and each group consisted of fish and two repetitions. The fish were divided and infected with Streptococcus agalactiae S13 (serotype Ib) and Francisella orientalis. The G1 group had a higher average final weight gain than the G2, G3, and NC groups. Further, a significant increase in the number of thrombocytes was observed in the groups administered probiotics in the diet (G1 and G3). A statistical difference was observed in the mortality of fish infected with S. agalactiae in the NC compared to the treated groups. Cetobacterium was the 43 most abundant genus in the intestinal microbiota of all groups, including the NC group. E. faecium increased the immunity of fish administered the treatment and decreased the mortality caused by S. agalactiae. As an autochtone probiotic, E. faecium does not interfere with the local ecosystem and thus has a great probiotic potential for Nile tilapia in Brazil. [ABSTRACT FROM AUTHOR]

In the present study, we evaluated the effects of administering Enterococcus faecium in food and/or water on the hematological and immunological parameters, intestinal microbiota, resistance to bacterial diseases (streptococcosis and francisellosis) and growth of Nile tilapia. Before the in vivo experiment, probiotic bacteria isolated from Nile tilapia were selected via inhibition tests. Sequencing, annotation, and assembly of the complete genome of the selected bacteria as well as other tests were performed using bioinformatics tools. Three treatments were implemented: G1 (probiotic feeding), G2 (probiotic in water), and G3 (probiotic in food and water); and a negative control (NC) was also employed. Treatment lasted 38 days, and each group consisted of fish and two repetitions. The fish were divided and infected with Streptococcus agalactiae S13 (serotype Ib) and Francisella orientalis. The G1 group had a higher average final weight gain than the G2, G3, and NC groups. Further, a significant increase in the number of thrombocytes was observed in the groups administered probiotics in the diet (G1 and G3). A statistical difference was observed in the mortality of fish infected with S. agalactiae in the NC compared to the treated groups. Cetobacterium was the 43 most abundant genus in the intestinal microbiota of all groups, including the NC group. E. faecium increased the immunity of fish administered the treatment and decreased the mortality caused by S. agalactiae. As an autochtone probiotic, E. faecium does not interfere with the local ecosystem and thus has a great probiotic potential for Nile tilapia in Brazil.

Tilmicosin (TMC), a semi-synthetic macrolide antibiotic, is widely used in veterinary medicine due to its broad-spectrum, bacteriostatic properties. Frequently administered in various birds species, it is likely used off-label in geese as well. The study sought to investigate TMC's pharmacokinetics, tissue residues, in geese through in vivo experiments. The study involved longitudinal open studies on 15 healthy adult males, with three phases separated by one-month washout periods. Geese were administered TMC through intravenous (IV, 5 mg/kg), subcutaneous (SC, 10 mg/kg), and oral (PO, 25 mg/kg for five consecutive days) routes, with blood samples drawn at specific intervals. Tissue samples were also collected for subsequent analysis at pre-assigned times. TMC in goose plasma was quantified by a fully validated HPLC method. Plasma concentrations were quantified up to 4 hr for the PO and IV routes, and up to 10 hr in the SC route. Significant variations in bioavailability were observed between SC (87%) and PO (4%) routes. The body extraction ratio was low at 0.03, suggesting minimal ability of the liver and kidneys to eliminate TMC. Multiple oral doses showed no plasma accumulation, but tissue data revealed extensive distribution and prolonged residence, up to 120 h, suggesting a sustained therapeutic effect despite the brief plasma half-life. Regarding the multiple PO doses, provisional withdrawal times of 6, 7.5, and 8 days were suggested for the liver, muscles, and kidneys, respectively, according to the MRL set for these matrices in chickens by EMA. In conclusion, while the practical oral administration is discouraged at the population level, SC administration of TMC may be appropriate for geese, albeit impractical for flock therapy., (© 2024 John Wiley & Sons Ltd.)

Drug delivery to the anterior or posterior segments of the eye is a major challenge due to the protection barriers and removal mechanisms associated with the unique anatomical and physiological nature of the ocular system. The paper presents the preparation and characterization of drug-loaded polymeric particulated systems based on pre-emulsion coated with biodegradable polymers. Low molecular weight biopolymers (chitosan, sodium hyaluronate and heparin sodium) were selected due to their ability to attach polymer chains to the surface of the growing system. The particulated systems with dimensions of 190–270 nm and a zeta potential varying from −37 mV to +24 mV depending on the biopolymer charges have been obtained. Current studies show that particles release drugs (dexamethasone/pilocarpine/bevacizumab) in a safe and effective manner, maintaining therapeutic concentration for a longer period of time. An extensive modeling study was performed in order to evaluate the drug release profile from the prepared systems. In a multifractal paradigm of motion, nonlinear behaviors of a drug delivery system are analyzed in the fractal theory of motion, in order to correlate the drug structure with polymer. Then, the functionality of a SL(2R) type “hidden symmetry” implies, through a Riccati type gauge, different “synchronization modes” (period doubling, damped oscillations, quasi-periodicity and intermittency) during the drug release process. Among these, a special mode of Kink type, better reflects the empirical data. The fractal study indicated more complex interactions between the angiogenesis inhibitor Bevacizumab and polymeric structure.

Research examining policy impacts on nicotine and cannabis co-use is important due to its high prevalence and adverse health effects. Important next steps to ensure rigor in policy research include: employing comprehensive policy exposure measurements; fully capturing routes of administration; and expanding existing research infrastructure. [ABSTRACT FROM AUTHOR]

Gabapentin has received increased attention due to a growing number of reports of misuse and diversion. However, significant details about gabapentin misuse are scant. Data are drawn from a mixed-methods study examining gabapentin misuse in South Florida. The sample includes 49 respondents who were age 18 or over and reported past year use of illicit opioids and/or the misuse of prescription opioid medications, as well as, recent (past 90 days) gabapentin misuse. Respondents were female (40.8%), Hispanic (30.6%), Black (16.3%), white (49.0%), and other race/ethnicity (4.1%). Mean age was 37.6. Many respondents (43%) misused gabapentin without ever receiving a prescription and 14% misused prior to being prescribed. Mean frequency of recent misuse was 25.4 days and included a mean of 51.65 pills/doses. Prevalent routes of administration included swallowing (85.7%) and snorting (10.2%). Gabapentin misuse occurred concomitantly with any opioid (44.9%), benzodiazepines (38.8%), alcohol (24.5%), and powder cocaine (24.5), among others. Respondents' descriptions indicate that gabapentin produces feelings reminiscent of alcohol intoxication or opioid-induced euphoria, but for some it produces no noticeable effect or only alleviates pain. Greater understanding of gabapentin misuse, especially associated behaviors and concomitant use is needed to inform prevention and intervention efforts, and to guide policy approaches. [ABSTRACT FROM AUTHOR]

In order to overcome some of the drawbacks of traditional formulations, increasing emphasis has recently been paid to lipid-based drug delivery systems. Solid lipid nanoparticles (SLNs) are among these delivery methods, and they hold promise because of their simplicity in production, capacity to scale up, biocompatibility, and biodegradability of formulation components. Other benefits could be connected to a particular route of administration or the makeup of the ingredients being placed into these delivery systems. This article aims to review the significance of solid lipid nanocarriers, their benefits and drawbacks, as well as their types, compositions, methods of preparation, mechanisms of drug release, characterization, routes of administration, and applications in a variety of delivery systems with a focus on their efficacy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This report assesses sociodemographic correlates of cannabis routes of administration (ROAs) among adolescents in 2017, one year prior to legalization of cannabis in Canada. We analyze a subsample of 809 students (Grades 9–12) from the Ontario Student Drug Use and Health Survey (OSDUHS) who used cannabis in the previous year. Pipes/bongs/waterpipes (81.8%) are the most prevalent ROA, followed by joints (73.8%) and edibles (42%). Approximately 70% of students report 2+ ROAs. Alcohol use in the previous year is associated with 2.28 (1.3–5.58 OR; 95% CI) times the odds of food/drink ROA and 2.91 (1.10–3.89; 95% CI) times the odds of joint ROA. Tobacco use is associated with 1.60 (1.07–2.41 OR; 95% CI) times the odds of blunt ROA, 2.07 (1.10–3.89; 95% CI) times the odds of pipe/bong/waterpipe ROA, and 1.75 (1.03–2.95 OR; 95% CI) times the odds of e-cigarette/vape pen/vaporizer ROA. Students who used alcohol have a rate 1.59 (1.08–2.36 IRR; 95% CI) times greater for total ROA count, and students who used tobacco have a rate 1.24 (1.09–1.40 IRR; 95% CI) times greater. Given young people's vulnerability to adverse outcomes associated with cannabis use, it is important to track ROA trends to inform harm reduction and educational programing and to evaluate impacts of policy changes. [ABSTRACT FROM AUTHOR]

During the recent years, more attentions have been focused on lipid base drug delivery system to overcome some limitations of conventional formulations. Among these delivery systems solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are promising delivery systems due to the ease of manufacturing processes, scale up capability, biocompatibility, and also biodegradability of formulation constituents and many other advantages which could be related to specific route of administration or nature of the materials are to be loaded to these delivery systems. The aim of this article is to review the advantages and limitations of these delivery systems based on the route of administration and to emphasis the effectiveness of such formulations.

The liposomes have continued to be well-recognized as an important nano-sized drug delivery system with attractive properties, such a characteristic bilayer structure assembling the cellular membrane, easy-to-prepare and high bio-compatibility. Extensive effort has been devoted to the development of liposome-based drug delivery systems during the past few decades. Many drug candidates have been encapsulated in liposomes and investigated for reduced toxicity and extended duration of therapeutic effect. The liposomal encapsulation of hydrophilic and hydrophobic small molecule therapeutics as well as other large molecule biologics have been established among different academic and industrial research groups. To date, there has been an increasing number of FDA-approved liposomal-based therapeutics together with more and more undergoing clinical trials, which involve a wide range of applications in anticancer, antibacterial, and antiviral therapies. In order to meet the continuing demand for new drugs in clinics, more recent advancements have been investigated for optimizing liposomal-based drug delivery system with more reproducible preparation technique and a broadened application to novel modalities, including nucleic acid therapies, CRISPR/Cas9 therapies and immunotherapies. This review focuses on the recent liposome' preparation techniques, the excipients of liposomal formulations used in various novel studies and the routes of administration used to deliver liposomes to targeted areas of disease. It aims to update the research in liposomal delivery and highlights future nanotechnological approaches. Unlabelled Image [ABSTRACT FROM AUTHOR]

Cyclosporine has been established as a gold standard for its immunosuppressant action. Apart from this, the molecule is boon in treating broad spectrum of diseases like rheumatoid arthritis, psoriasis, and dry eye syndrome. The broad spectrum of cyclosporine demands efficient delivery systems by several routes. Neoral® and Sandimmune® are currently available formulations for oral route, whereas Restasis® is used for ocular delivery of cyclosporine. The available formulations serve the purpose only to a limited extent due to constraints like high molecular weight, low solubility, low permeability, bitter taste, and narrow therapeutic index of cyclosporine. Therefore, several novel formulations like microemulsion, self-emulsifying systems, nanoparticles, and microspheres were developed to overcome these constraints, exploring different routes like oral, ocular, and topical for cyclosporine. Additionally, iontophoresis and ultrasound-mediated delivery has also been studied to improve its poor permeability in topical delivery, whereas biodegradable implants were reported to increase the retention time in cornea and prolonged the release of cyclosporine by ocular route. Although these recent advances in cyclosporine delivery look promising, its clinical translation require in depth studies to deliver safe, efficacious, and stable formulation of cyclosporine. This review focuses on challenges of cyclosporine delivery and the recent advancements for overcoming the constraints. [ABSTRACT FROM AUTHOR]

Hapten contact hypersensitivity (CHS) elicits a well-documented inflammation response that can be used to illustrate training of immune cells through hapten-specific CHS memory. The education of hapten-specific memory T cells has been well-established, recent research in mice has expanded the “adaptive” characteristic of a memory response from solely a function of the adaptive immune system, to innate cells as well. To test whether similar responses are seen in a non-rodent model, we used hapten-specific CHS to measure the ear inflammation response of outbred pigs to dinitrofluorobenzene (DNFB), oxazolone (OXA), or vehicle controls. We adapted mouse innate memory literature protocols to the domestic pig model. Animals were challenged up to 32 days post initial sensitization exposure to the hapten, and specific ear swelling responses to this challenge were significant for 7, 21, and 32 days post-sensitization. We established hapten-specific CHS memory exists in a non-rodent model. We also developed a successful protocol for demonstrating these CHS responses in a porcine system. [ABSTRACT FROM AUTHOR]

Introduction: Ethiopian pharmaceutical sector has been facing inaccessibility and unaffordability to key essential medicines due to medicines diversion from the public to private health care facilities, lack of transparency, poor inventory management, and poor dispensing workflow. In an effort to improve the pharmaceutical sector, the government of Ethiopia in 2011 introduced Auditable Pharmaceutical Transactions and Services program. This study intended to compare drug use indicators in auditable and non-auditable primary level hospitals. Methods: A cross-sectional comparative study was conducted between January 2018 and December 2018 at primary level hospitals in southern Ethiopia: one with Auditable Pharmaceutical Transactions and Services (APTS) program; another without APTS (Non-APTS).WHO drug use indicators in auditable primary hospitals (n = 10) and similar non-auditable primary hospitals (n = 10) were compared. The prescribing indicators and average cost of medicines were evaluated retrospectively using 1000 prescriptions from each group. Patient care indicators were evaluated prospectively by interviewing and observing 1000 patients from each group. Patient satisfaction was assessed by interviewing 1000 patients from each group. Health care facilities were evaluated through observation. We performed descriptive analysis, t-test, logistic regression, Mann-Whitney U test and linear regression using SPSS version 20.0. Results: The mean consultation time in auditable and non-auditable hospitals was found to be 6.5 minutes and 3.46 minutes, respectively. The average dispensing time in auditable and non-auditable hospitals was found to be 6.6 minutes and 1.02 minutes, respectively.The proportion of drugs actually dispensed was 97.59% in APTS facilities and 76.44% in the non-auditable facilities with the lowest value seen in a non-auditable facility (51.65%). The average number of drugs per prescription was 2.32 (±1.26) and 2.84 (±1.17) in auditable and non-auditable facilities, respectively. The level of patient satisfaction on the convenience of pharmacy location, information on contraindications, availability of drugs and amount of time for counseling was significantly higher in the auditable facilities than the non-auditable facilities (p<0.001). Conclusions: This study revealed that patient care indicator values, the level of patient satisfaction on the pharmacy services and health facility indicator values were significantly better in APTS than Non-APTS primary level hospitals. Most of prescribing indicators and labeling practices were not met WHO stated standard in both auditable and non-auditable facilities.This indicates that the auditable programshould include additional strategies to reverse the existing irrational prescribing and inadequate labeling practices. [ABSTRACT FROM AUTHOR]

Electrical impedance myography (EIM) is a technique for the assessment of muscle health and composition and has been shown to be sensitive to a variety of muscle pathologies including neurogenic atrophy and connective tissue deposition. However, it has been minimally studied in pure inflammation. In this study, we sought to assess EIM sensitivity to experimental inflammation induced by the localized intramuscular injection of λ-carrageenan. A total of 91 mice underwent 1–1000 kHz EIM measurements of gastrocnemius using a needle array, followed by injection of either 0.3% λ-carrageenan in phosphate-buffered saline (PBS) or PBS alone. Animals were then remeasured with EIM at 4, 24, 48, or 72 hours and euthanized and quantitative assessment of muscle histology was performed. Parallel alterations in both 5 and 50 kHz EIM values were identified at 4 and 24 hours, including reductions in phase, reactance, and resistance. In PBS-treated animals these values normalized by 48 hours, whereas substantial reductions in phase and reactance in 5 kHz EIM values persisted at 48 and 72 hours (i.e., values of phase 72 hours post-injection were 6.51 ± 0.40 degrees for λ-carrageenan versus 8.44 ± 0.35 degrees for PBS p<0.001, n = 11 per group). The degree of basophilic area observed in muscle sections by histology correlated to the degree of phase change at these two time points (Rspearman = -0.51, p = 0.0029). Changes in low frequency EIM parameters are sensitive to the presence of inflammatory infiltrates, and have the potential of serving as a simple means of quantifying the presence and extent of muscle inflammation without the need for biopsy. [ABSTRACT FROM AUTHOR]

Objective: We assessed the impact of intravenous (IV) infusion versus intramuscular (IM) oxytocin on postpartum blood loss and rates of postpartum hemorrhage (PPH) when administered during the third stage of labor. While oxytocin is recommended for prevention of PPH, few double-blind studies have compared outcomes by routes of administration. Methods: A double-blind, placebo-controlled randomized trial was conducted at a hospital in Argentina. Participants were assigned to receive 10 IU oxytocin via IV infusion or IM injection and a matching saline ampoule for the other route after vaginal birth. Blood loss was measured using a calibrated receptacle for a 1-hour minimum. Shock index (SI) was also calculated, based on vital signs measurements, and additional interventions were recorded. Primary outcomes included: the frequency of blood loss ≥500ml and mean blood loss. Results: 239 (IV infusion) and 241 (IM) women were enrolled with comparable baseline characteristics. Mean blood loss was 43ml less in the IV infusion group (p = 0.161). Rates of blood loss ≥500ml were similar (IV infusion = 21%; IM = 24%, p = 0.362). Women in the IV infusion group received significantly fewer additional uterotonics (5%), than women in the IM group (12%, p = 0.007). Women with PPH in the IM group experienced a larger increase in SI after delivery, which may have influenced recourse to additional interventions. Conclusions: The route of oxytocin administration for PPH prevention did not significantly impact measured blood loss after vaginal birth. However, differences were observed in recourse to additional uterotonics, favoring IV infusion over IM. In settings where IV lines are routinely placed, oxytocin infusion may be preferable to IM injection. [ABSTRACT FROM AUTHOR]

Aim: There is no consensus regarding the association between hormone replacement therapy (HRT) and risk of meningioma so far. We conducted the first study among Chinese female patients to investigate the influence of HRT use on the risk of meningioma. Methods: We retrospectively collected records of diagnosis of meningioma for women aged 50 years and above during 2011–2016 and dispense of HRT prior to meningioma diagnosis in three tertiary hospitals in China. Meningioma cases were matched with controls at a ratio of 1:2 by using nearest neighbor propensity scores matching in order to balance the baseline characteristics between groups, which generated a total of 629 cases with 1258 controls. Results: We observed prior use of HRT associated with increased risk of meningioma (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0–1.4) and the association was more prominent among women having multiple HRT dispenses and longer term exposure (OR, 1.3; 95% CI, 1.1–1.6), among those with combination therapy of estrogens and progestogens (OR, 1.3; 95% CI, 1.1–1.7) than monotherapy, and among progestogen users than estrogen users as for monotherapy. Furthermore, vaginal, subcutaneous implant seems to be associated with a higher risk of meningioma compared with oral administration although no significance had been reached. Conclusion: This case–control study provides evidence that hormone use for an HRT purpose might constitute the development and growth of meningioma as an independent risk factor, especially for combination therapy and/or long‐term users, which supports that meningioma might be a hormone‐sensitive tumor. [ABSTRACT FROM AUTHOR]

Pain management in palliative care is both an art and a science. Essential to good pain control is an understanding not only of the pathophysiology of the origin of the pain, but also the impact that the pain is having, as the palliative patient may have to live with the symptoms of disease for months or even years. Interventions can then be targeted and at various times, may include a range of pharmacological treatments, psychological or spiritual support and possibly the involvement of other specialties to alleviate a particular problem. [ABSTRACT FROM AUTHOR]