Self-Emulsifying Drug Delivery System for Enhanced Oral Delivery of Tenofovir: Formulation, Physicochemical Characterization, and Bioavailability Assessment.

Tenofovir (TNF) is a common component of many antiretroviral therapy regimens, but it is associated with poor membrane permeability and low oral bioavailability. To improve its oral bioavailability and membrane permeability, a self-emulsifying drug delivery system (SEDDS) was developed and characterized, and its relative bioavailability was compared to the marketed tablets (Tenof). Based on solubility and ternary phase diagram analysis, eucalyptus oil was selected as an oil phase, Kolliphor EL, and Kollisolv MCT 70 were chosen as surfactant and cosurfactant, respectively, while glycerol was used as cosolvent in surfactant mixture. Optimized SEDDS formulation F6 showed an oil droplet size of 98.82 nm and zeta potential of -13.03 mV, indicating the high stability of oil droplets. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy characterization studies were also carried out to assess the amorphous and morphological states of the drug in the prepared SEDDS formulation. The in vitro dissolution profile of SEDDS shows the rapid release of the drug. SEDDS F6 demonstrates a higher drug permeability than the plain TNF and TNF-marketed tablets (Tenof). A pharmacokinetic study in rats revealed that SEDDS F6 showed significantly higher Cmax and AUC0-t than the marketed tablets and pure drug suspension. In addition, the relative bioavailability of SEDDS formulation dramatically improved by 21.53-fold compared to marketed tablets and 66.27-fold compared to pure drugs. These findings show that SEDDS composed of eucalyptus oil, glycerol, Kolliphor EL, and Kollisolv MCT 70 could be a useful tool for enhancing physiochemical properties and oral TNF absorption. Therefore, SEDDS has shown promise in improving the oral bioavailability of poorly water-soluble drugs.

Phytochemical profiling and anti-inflammatory, analgesic activity of Ficus religiosa L. and molecular docking study against iNOS, TNF-α enzyme.

Ficus religiosa L., a member of the Moraceae family, is a medicinal plant having a number of pharmacological properties. The anti-inflammatory and analgesic actions of an ethanolic extract of F. religiosa bark FRE (at 100 and 200mg/kg dosages) and the biomarker component quercetin QC (at 5 and 10mg/kg doses) were investigated. The estimate of quercetin was carried by using an HPTLC analysis of FRE. Additionally, qualitative and quantitative screening for key important phytocomponents was done using dried, ground plant stem barks. By using molecular docking, the molecular interaction profile with several anti-inflammatory drug targets was examined. Both the FRE as well as QC showed a substantial decline in paw volume when compared with the relevant control groups (p<0.01 & p<0.001). Following the administration of acetic acid to mice, the FRE and QC both demonstrate a substantial lengthening of the paw licking or leaping towards Eddy's hot plate as well as a decrease in the number of writhes (p<0.01 & p<0.001). This study supports the use of these herbs in conventional medicine to treat pain and inflammation by through similar mechanism as compound quercetin (QC).

Production, Characterization, and In Vitro and In Vivo Studies of Nanoemulsions Containing St. John's Wort Plant Constituents and Their Potential for the Treatment of Depression.

The current project was designed to prepare an oil-in-water (oil/water) hypericin nanoemulsion using eucalyptus oil for the preparation of an oil phase with chitosan as an emulsion stabilizer. The study might be a novelty in the field of pharmaceutical sciences, especially in the area of formulation development. Tween® 80 (Polysorbate) was used as the nonionic surfactant. The nanoemulsion was prepared by using the homogenization technique, followed by its physicochemical evaluation. The surface morphological studies showed the globular structure has a nano-sized diameter, as confirmed by zeta size analysis. The zeta potential analysis confirmed a positive surface charge that might be caused by the presence of chitosan in the formulation. The pH was in the range of 5.14 to 6.11, which could also be compatible with the range of nasal pH. The viscosity of the formulations was found to be affected by the concentration of chitosan (F1-11.61 to F4-49.28). The drug release studies showed that the presence of chitosan greatly influenced the drug release, as it was noticed that formulations having an elevated concentration of chitosan release lesser amounts of the drug. The persistent stress in the mouse model caused a variety of depressive- and anxiety-like behaviors that can be counteracted by chemicals isolated from plants, such as sulforaphane and tea polyphenols. In the behavioral test and source performance test, hypericin exhibited antidepressant-like effects. The results show that the mice treated for chronic mild stress had a considerably higher preference for sucrose after receiving continuous hypericin for 4 days (p = 0.0001) compared to the animals administered with normal saline (p ≤ 0.0001) as well as the naïve group (p ≤ 0.0001). In conclusion, prepared formulations were found to be stable and can be used as a potential candidate for the treatment of depression.

Global Epidemiology, Clinical Features, Diagnosis and Current Therapeutic Novelties in Migraine Therapy and their Prevention: A Narrative Review.

INTRODUCTION: The current article reviews the latest information on epidemiology, clinical features, diagnosis, recent advancements in clinical management, current therapeutic novelties, and the prevention of migraines. In a narrative review, all studies as per developed MeSH terms published until February 2023, excluding those irrelevant, were identified through a PubMed literature search. METHODS: Overall, migraine affects more than a billion people annually and is one of the most common neurological illnesses. A wide range of comorbidities is associated with migraines, including stress and sleep disturbances. To lower the worldwide burden of migraine, comprehensive efforts are required to develop and enhance migraine treatment, which is supported by informed healthcare policy. Numerous migraine therapies have been successful, but not all patients benefit from them. RESULTS: CGRP pathway-targeted therapy demonstrates the importance of translating mechanistic understanding into effective treatment. In this review, we discuss clinical features, diagnosis, and recently approved drugs, as well as a number of potential therapeutic targets, including pituitary adenylate cyclase-activating polypeptide (PACAP), adenosine, opioid receptors, potassium channels, transient receptor potential ion channels (TRP), and acid-sensing ion channels (ASIC). CONCLUSION: In addition to providing more treatment options for improved clinical care, a better understanding of these mechanisms facilitates the discovery of novel therapeutic targets.

Assessment of thermal comfort in a hot and humid indoor built environment of a kitchen at a university canteen.

BACKGROUND: The hot and humid environment inside the kitchen is a cumulative sign of health impact that deteriorates the well-being and productivity of cooking workers, which could be a barrier to thermal comfort. As the cooking task progresses throughout the day, uncomfortable thermal conditions inside a kitchen work environment may diminish the work quality of the kitchen workers. OBJECTIVE: The objectives of the study were to evaluate the measured environmental factors of thermal comfort during various cooking periods [morning, day, evening, night] and examine the occupant's perception votes followed by further investigating the worker's thermal comfort conditions using PMV, PPD, SET, WBGT, and TSI indices. METHODS: The study was carried out inside the kitchen of the university canteen at IIT Guwahati, India. The objective and subjective measurements were accomplished during the summer season, while CBE thermal comfort software was employed for calculating the thermal comfort indices like PMV, PPD, and SET. RESULTS: The results of this study revealed that during entire cooking time, the recorded environmental factors of thermal comfort were found outside the recommended limits as per ASHRAE-55 standard, which indicates very hot prevalent conditions. Also, cook's perception vote (TSV, TCV) for the existing environment did not follow the central three categories of votes (+1, 0, -1), even the cooking workers were also not satisfied with the prevailing environmental conditions, as 88% subjects responded dissatisfaction with the thermal environment. While, estimated values of thermal comfort indices (PMV, PPD, and SET) designated morning time cooking period slightly comfortable than the other cooking periods, but still not accordance with the ASHRAE-2017 standard. The WBGT index designated day cooking period as hazardous, with rest of cooking periods under severe risk level. In contrast, the TSI index indicated entire cooking periods under "slightly warm" thermal sensation. CONCLUSION: The assessment of this study showed that the existing kitchen environment of the university canteen is not conducive for workers. Improper ventilation design may cause the overheating inside the kitchen, which may increase the dissatisfaction rate of the employed workers and also affects the energy savings in the kitchen environment, which helps maintain thermal comfort. Further studies are required to improve the thermal comfort of the kitchen occupants by providing proper design interventions based on heating and cooling air ventilation systems.

An Updated Review on Therapeutic Potential and Recent Advances in Drug Delivery of Berberine: Current Status and Future Prospect.

Natural products are well known for their high potency with minimum side effects. Plant extracts are the most commonly used natural products because of their ease of availability and relatively low production cost. Berberine (BBR), a phytochemical component of some Chinese medicinal herbs (most commonly Berberis vulgaris), is an isoquinoline alkaloid with several biological and pharmacological effects including antioxidant, anti-inflammatory, antitumour, antimicrobial, antidepressant, hepatoprotective, hypolipidemic, and hypoglycemic actions. Interestingly, multiple studies have shown that BBR is a potential drug candidate with a multi-spectrum therapeutic application. However, the oral delivery of BBR is challenged owing to its poor bioavailability. Therefore, its oral bioavailability needs to be enhanced before it can be used in many clinical applications. This review provides an overview of the various studies that support the broad range of pharmacological activities of BBR. Also, it includes a section to address the issues and challenges related to the drug and methods to improve the properties of BBR, such as solubility, stability and bioavailability that may be explored to help patients reap the maximum benefit from this potentially useful drug.

Development of Natural Polysaccharide-Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment.

The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the P-gp expressed in the intestinal lumen. Therefore, we aimed to design and fabricate a nanoparticulate system for delivery of BBR employing naturally derived biodegradable and biocompatible polymers, mainly chitosan and alginate, to enhance the oral bioavailability of BBR. A chitosan-alginate nanoparticle system loaded with BBR (BNPs) was formulated by ionic gelation method and was optimized by employing a three-factor, three-level Box-Behnken statistical design. BNPs were characterized for various physicochemical properties, ex vivo, and in vivo evaluations. The optimized BNPs were found to be 202.2 ± 4.9 nm in size, with 0.236 ± 0.02 of polydispersity index, zeta potential -14.8 ± 1.1 mV, and entrapment efficiency of 85.69 ± 2.6%. BNPs showed amorphous nature with no prominent peak in differential scanning calorimetry (DSC) investigation. Similarly, fourier-transform infrared spectroscopy (FTIR) studies did not reveal any interaction between BBR and excipients used. The drug release followed Higuchi kinetics, since these plots demonstrated the highest linearity (R2 = 0.9636), and the mechanism of release was determined to be anomalous or non-Fickian in nature. An ex-vivo gut permeation study showed that BNPs were better internalized into the cells and more highly permeated through the intestine. Furthermore, in vivo pharmacokinetic analysis in female Wistar rats showed a 4.10-fold increase in the oral bioavailability of BBR from BNPs as compared to BBR suspension. With these findings, we have gained new insight into the effective delivery of poorly soluble and permeable drugs via a chitosan-alginate nanoparticle system to improve the therapeutic performance of an oral nanomedicine.

Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis.

INTRODUCTION: Betamethasone dipropionate (BD) has anti-inflammatory, immunomodulatory, and antiproliferative activity. The aim of the current work was to test the hypothesis that the addition of corticosteroid such as BD and a keratolytic agent such as salicylic acid in nanocarrier based microemulsions formulation would result in enhancement and sustaining of corticosteroid delivery rate leading to better anti-psoriatic activity. Clinical use of BD is restricted to some extent due to its poor permeability across the skin. So to increase its permeation across the skin, microemulsion-based gel formulations were prepared and characterised. MATERIALS AND METHODS: Microemulsions were prepared by aqueous phase titration method, using oleic acid:sefsol (1.5:1), Tween 20, isopropyl alcohol, and distilled water as the oil phase, surfactant, cosurfactant and aqueous phase, respectively. Selected formulations were subjected to physical stability studies and consequently in vitro skin permeation studies. Surface studies of optimized formulation were done by transmission electron microscopy. In vivo anti-inflammatory activity was done by carageenan-induced raw paw edema method. RESULTS: The droplet size of microemulsions ranged from 60 to 190 nm. The optimized formulation exhibited viscosity 28.55 ± 2.03 mP, refractive index 1.409, pH 6.4, and conductivity 10(-4) scm(-1). The optimized microemulsion was converted into hydrogel using carbopol 934, and salicylic acid was incorporated into it. Drug deposition in skin was found to be 29.73 µg/mg. Assessment of skin permeation was done by histopathology studies which indicated changes in the structure of epidermal membrane of skin. In vivo anti-inflammatory activity indicated 72.11% and 43.96% inhibition of inflammation in case of developed microemulsion gel and marketed gel, respectively. CONCLUSIONS: The developed microemulsion gel containing BD and salicylic acid provided sustained and good anti-inflammatory activity for the treatment of psoriasis.