Biomaterial-based delivery platforms for transdermal immunotherapy.

Nowadays, immunotherapy is one of the most essential treatments for various diseases and a broad spectrum of disorders are assumed to be treated by altering the function of the immune system. For this reason, immunotherapy has attracted a great deal of attention and numerous studies on different approaches for immunotherapies have been investigated, using multiple biomaterials and carriers, from nanoparticles (NPs) to microneedles (MNs). In this review, the immunotherapy strategies, biomaterials, devices, and diseases supposed to be treated by immunotherapeutic strategies are reviewed. Several transdermal therapeutic methods, including semisolids, skin patches, chemical, and physical skin penetration enhancers, are discussed. MNs are the most frequent devices implemented in transdermal immunotherapy of cancers (e.g., melanoma, squamous cell carcinoma, cervical, and breast cancer), infectious (e.g., COVID-19), allergic and autoimmune disorders (e.g., Duchenne's muscular dystrophy and Pollinosis). The biomaterials used in transdermal immunotherapy vary in shape, size, and sensitivity to external stimuli (e.g., magnetic field, photo, redox, pH, thermal, and even multi-stimuli-responsive) were reported. Correspondingly, vesicle-based NPs, including niosomes, transferosomes, ethosomes, microemulsions, transfersomes, and exosomes, are also discussed. In addition, transdermal immunotherapy using vaccines has been reviewed for Ebola, Neisseria gonorrhoeae, Hepatitis B virus, Influenza virus, respiratory syncytial virus, Hand-foot-and-mouth disease, and Tetanus.

3D Printing of Dental Prostheses: Current and Emerging Applications.

Revolutionary fabrication technologies such as three-dimensional (3D) printing to develop dental structures are expected to replace traditional methods due to their ability to establish constructs with the required mechanical properties and detailed structures. Three-dimensional printing, as an additive manufacturing approach, has the potential to rapidly fabricate complex dental prostheses by employing a bottom-up strategy in a layer-by-layer fashion. This new technology allows dentists to extend their degree of freedom in selecting, creating, and performing the required treatments. Three-dimensional printing has been narrowly employed in the fabrication of various kinds of prostheses and implants. There is still an on-demand production procedure that offers a reasonable method with superior efficiency to engineer multifaceted dental constructs. This review article aims to cover the most recent applications of 3D printing techniques in the manufacturing of dental prosthetics. More specifically, after describing various 3D printing techniques and their advantages/disadvantages, the applications of 3D printing in dental prostheses are elaborated in various examples in the literature. Different 3D printing techniques have the capability to use different materials, including thermoplastic polymers, ceramics, and metals with distinctive suitability for dental applications, which are discussed in this article. The relevant limitations and challenges that currently limit the efficacy of 3D printing in this field are also reviewed. This review article has employed five major scientific databases, including Google Scholar, PubMed, ScienceDirect, Web of Science, and Scopus, with appropriate keywords to find the most relevant literature in the subject of dental prostheses 3D printing.

Does trigonelline help skin tone? Molecular docking studies of trigonelline on the human tyrosinase, formulation, optimization, and characterization of an emulgel-containing Trigonella foenum-graecum L. fenugreek standardized hydroalcoholic extract.

AIMS: This study aimed to perform molecular docking studies to identify possibilities of the inhibitory potential of the trigonelline present in fenugreek seeds on the human tyrosinase, standardize fenugreek extract, formulate, and characterize an emulgel-containing fenugreek extract-entrapped niosomal vesicles. MATERIALS AND METHODS: The docking study was performed using AutoDock software. The extract was standardized by the RP-HPLC method. Emulgels containing fenugreek extract and fenugreek extract-entrapped niosomes were optimized by the D-optimal method. In vitro characterization and stability studies were also carried out. RESULTS: The lowest energy docked poses of trigonelline on the human tyrosinase complex was calculated -5.8 kcal/mol. Also, in vitro assessment of the tyrosinase inhibitory effect of trigonelline and comparison of IC50 values of trigonelline and kojic acid revealed that the enzyme inhibition efficacy of trigonelline was stronger than that of kojic acid. Optimization led to emulgels with desired viscosity, droplet size, and spreadability values. The release study showed that trigonelline was released from the niosomes at a lower rate compared with extract containing emulgel. Permeation investigations revealed that trigonelline in niosomes has a higher ability to permeate through the skin. CONCLUSION: In conclusion, in silico and in vitro studies have shown that trigonelline can be assumed as an appropriate candidate for developing new cosmetic preparations and nonionic surfactant vesicles help trigonelline to permeate through the skin to a higher extent. However, clinical trials should be performed to confirm these findings.

Evaluation of the efficacy and safety of Melatonin in moderately ill patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. INCLUSION CRITERIA: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin capsules at a dose of 50 mg daily for a period of seven days. CONTROL GROUP: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1ß (IL-1ß), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients randomized into two groups (30 in each group). TRIAL STATUS: The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N5 ". The registration date was 14 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Nose-to-brain delivery of sumatriptan-loaded nanostructured lipid carriers: preparation, optimization, characterization and pharmacokinetic evaluation.

OBJECTIVES: Migraine is a neurological disorder with unilateral pulsatile headache which can affect the functions of sufferers. Migraineurs experience some undesirable symptoms such as pain, nausea, vomiting and in some cases auras which make the oral delivery non-selective. The lipid nanoparticles are considered as good carriers for nose-to-brain drug delivery. The present study aimed to formulate and evaluate a sumatriptan-loaded nanostructured lipid carrier (NLC). METHODS: A drug-loaded NLC was optimized using D-optimal design of experiment and then the characterization of the formulated NLC including particle size, zeta potential, electron microscopy, thermal analysis, drug loading efficiency and release kinetics were carried out. Pharmacokinetic evaluations were also performed during an in-vivo study on Sprague-Dawley rats and neuropharmacokinetic parameters such as drug targeting efficiency (DTE) and direct transport percentage (DTP) were calculated. KEY FINDINGS: The optimization of experiments led to nanoparticles with 101 nm mean diameter and polydispersity index (PDI) of 0.27. The drug entrapment efficiency (EE) for optimized nanoparticle was found to be 91.00%. DTE and DTP of intranasal-administered NLC were calculated 258.02% and 61.23%, respectively. CONCLUSIONS: Neuropharmacokinetic evaluation of intranasal NLC dispersion represents a suitable brain delivery system. The DTP of NLC formulation suggests the desirable entrance of sumatriptan into the brain.

Pharmacists' Knowledge and Attitudes Towards Upper Respiratory Infections (URI) in Iran: A Cross Sectional Study.

OBJECTIVES: To identify the knowledge and attitudes of community pharmacists towards upper respiratory infections. SETTING: The pharmacists, who participated in an annual clinical pharmacy congress in Tehran, were enrolled in this study. INTERVENTION: We conducted a cross-sectional descriptive study to assess the knowledge and attitudes of 72 community pharmacists towards upper respiratory infections (URI) using a questionnaire. MAIN OUTCOME MEASURES: We investigated the knowledge and attitudes of pharmacists towards rational antibiotics use in URI in Iran. Also we tried to detect causes of irrational antibiotic use. RESULTS: The response rate of our study was 72%. Of all respondents, 98.61% answered the knowledge question" inappropriate use of antibiotics could lead to drug resistance and would increase drug allergy" correctly. More than half (55.56%) of the community pharmacists believed that pharmacists can be affected by patients' expectations for antibiotics prescription. A majority of pharmacists gave a correct response to questions about beneficial use of corticosteroid in URI (90.28%) and symptoms persistent after 10-14 days even with antibiotic therapy (86.11%). More than half of all pharmacists had misconceptions on antibiotic use for URI in children under 2 years old. More than half of all pharmacists believed that most cases of URI are viral infections. Also, 90.28% of all pharmacists believed that guidelines for antibiotics prescribing may be beneficial in appropriate antibiotic use. CONCLUSION: According to a high response rate for the question about efficiency of antibiotics prescription guidelines, reliable information on the appropriate use of antibiotics should be more widely available for pharmacists.

Management of Acute Diarrhea: A Study on Community Pharmacists' Attitudes in Iran.

Diarrhea disease is one of the most important problem which leads to mortality and morbidity in under developing country. Pharmacists play an important role in providing health services to local communities for this common health issues. The purpose of our study was to assess diarrhea related attitude and knowledge of pharmacist in Iran. This study has been performed in Iranian Pharmacist Association congress in 2012. This is conducted as a questionnaire base, in 100 randomly Persian pharmacists, consists of questions about demographic data of pharmacists such as age, sex, college, year of study, attitude and knowledge of pharmacists on management of acute diarrhea. Pharmacists believed that it was important to ask about the age of patients (98%), initiation (98%) and frequency (95%) of diarrhea, blood (90%) in diarrhea, other symptoms such as fever or pain (95%) as well as recent foods consumption (91%). However there was a significance differences between male and female pharmacist about their diarrhea knowledge. Among pharmacists, 75% asked about the recent travel and 63% asked about other affected family members .Most pharmacists (78) dispensed ORS for the pediatric acute diarrhea. However, some believed in recommending ORS+antimotility drugs (9%), ORS+antismaspolitic (11%) and ORS+antibiotics (2 %). Although Iranian pharmacist were in a good attitude however the rule of periodic studies should highlighted.