DARU Journal of Pharmaceutical Sciences最新文献

Objectives: In the recent years, in-situ hydrogel based on gellan gum has been investigated for delivery of various drug molecules particularly to treat neurological disorders via intranasal route. The major objective of the present manuscript is to review the recent research studies exploring gellan gum as ionic triggered in-situ gel for intranasal administration to enhance absorption of drugs and to increase their therapeutic efficacy.

Methods: This review include literature from 1982 to 2023 and were collected from various scientific electronic databases like Scopus, PubMed and Google Scholar to review source, chemistry, ionotropic gelation mechanism, and recent research studies for gellan gum based in-situ hydrogel for intransasl administration.Keywords such as gellan gum, in-situ hydrogel, intranasal administration and brain targeting were used to search literature. The present review included the research studies which explored gellan gum based in-situ gel for intranasal drug delivery.

Results: The findings have shown enhanced biavailability of various drugs upon intranasal administration using gellan-gum based in-situ hydrogel.Moreover, the review indicated that intranasal administration of in-situ hydrogel facilitate to overcome blood brain barrier effectively. Hence, significantly higher drug concentration was found to be achieved in brain tissues upon intranasal administration than that of other routes like oral and intravenous.

Conclusion: The present work conducted a comprehensive review for gellan gum based in-situ hydrogel particularly for intransal administration to overcome BBB. The study concluded that gellan gum based in-situ hydrogel could be potential promising delivery system for intranasal administration to improve bioavailability and efficacy of drugs specifically to treat neurological disorders.

Background: A persistent difficult-to-treat cough can be exhausting. Iron is an essential element that plays an important role in regulating the production of pro-inflammatory cytokines, and its deficiency may potentiate airway inflammation and dysfunction. There is a paucity of data regarding a link between iron deficiency (ID) and idiopathic cough.

Objectives: In this study, a case of persistent non-productive cough, which was unresponsive to targeted treatment approaches but responsive to iron therapy, is reported.

Methods: A 53-year-old woman came to a medical clinic with complaints of a chronic and progressive non-productive cough. She underwent a complete clinical and paraclinical evaluation.

Results: Her vital signs were stable and no abnormalities were found on the physical examination. The results of the spirometry and chest radiography were unremarkable. The laboratory test indicated hypochromic microcytic anemia, with a hemoglobin value of 9.6 g/dL. Her cough was resolved after treatment of iron-deficiency anemia with an oral nutraceutical capsule containing 28 mg of elemental iron (as ferrous bis-glycinate) plus folic acid, vitamin B12, and vitamin C, once daily for six months.

Conclusion: In the case of unexplained chronic cough, resistant to targeted therapies, investigation and treatment of ID may contribute to the resolution of cough.

Background: Rhinovirus (RV) infection is a major cause of common colds and asthma exacerbations, with no antiviral drug available. Curcumin exhibits broad-spectrum antiviral activities, but its therapeutic effect is limited by a poor pharmacokinetics profile. Curcumin-like diarylpentanoid analogs, particularly 2-benzoyl-6-(3,4-dihydroxybenzylidene)cyclohexen-1-ol (BDHBC) and 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), have better solubility and stability compared to curcumin.

Objectives: Therefore, this study aims to evaluate and compare the antiviral effects of curcumin, BDHBC, and DHHPD in an in vitro model of RV infection.

Methods: The inhibitory effects on RV-16 infection in H1 HeLa cells were assessed using cytopathic effect (CPE) reduction assay, virus yield reduction assay, RT-qPCR, and Western blot. Antiviral effects in different modes of treatment (pre-, co-, and post-treatment) were also compared. Additionally, intercellular adhesion molecule 1 (ICAM-1) expression, RV binding, and infectivity were measured with Western blot, flow cytometry, and virucidal assay, respectively.

Results: When used as a post-treatment, BDHBC (EC₅₀: 4.19 µM; SI: 8.32) demonstrated stronger antiviral potential on RV-16 compared to DHHPD (EC₅₀: 18.24 µM; SI: 1.82) and curcumin (less than 50% inhibition). BDHBC also showed the strongest inhibitory effect on RV-induced CPE, virus yield, vRNA, and viral proteins (P1, VP0, and VP2). Furthermore, BDHBC pre-treatment has a prophylactic effect against RV infection, which was attributed to reduced basal expression of ICAM-1. However, it did not affect virus binding, but exerted virucidal activity on RV-16, contributing to its antiviral effect during co-treatment.

Conclusion: BDHBC exhibits multiple antiviral mechanisms against RV infection and thus could be a potential antiviral agent for RV.

Background: Over the past decades, a substantial portion of the population worldwide has been infected with varicella zoster and most cases developed shingles. Unfortunately, shingles is usually accompanied by postherpetic neuralgia, which may persist for months to years after the resolution of the viral infection.

Objectives: Gabapentin is an orally gamma-aminobutyric acid analogue approved by the Food and Drug Administration to manage shingles postherpetic neuralgia. However, gabapentin shows nonlinear pharmacokinetics, with variable absorption and bioavailability along with its short half-life and long side effects that may include dizziness and somnolence, which calls for an appropriate topical dosage form. Bigels are unique semisolid dosage forms with boosted penetrability and satisfactory hydrophilic texture.

Methods: The current work pointed to formulating gabapentin-loaded bigels for the treatment of postherpetic neuralgia, where the analysis and optimization of design were performed via Design-Expert®.

Results and conclusions: The selected bigel (F5), incorporating 400 mg Span 60, 1000 mg Tween 80, and 1000 mg Transcutol, displayed spherical nanosized particles with acceptable viscosity and spreadability. Subsequent topical application of the selected bigel on the skin of Wistar rats, F5, demonstrated a boosted accumulation of gabapentin in the skin similar to PLO gel but superior to the drug solution. Furthermore, a histopathological study demonstrated the biosafety of the selected bigel when applied topically. Accordingly, gabapentin-loaded bigel would be considered a potentially topical dosage form for the delivery of gabapentin for the management of postherpetic neuralgia.

Background: Nilotinib (NIL) is a prescription medication employed in the treatment of specific types of leukemia, namely chronic myelogenous leukemia (CML). The determination of NIL levels in patients undergoing treatment for CML is of paramount importance for effective management of treatment and toxicity. Also, monitoring and controlling its level in wastewater sources could help scientists to identify potential hotspots of contamination and take appropriate measures to mitigate their impact on the environment and public health.

Objectives: This study presents a D-µ-SPE technique utilizing two MOFs as adsorbents for the efficient detection of nilotinib in plasma and wastewater samples for the first time.

Methods: Two highly effective MOFs, MIL-101(Fe) and MIL-53(Al), were synthesized and applied as dispersive micro-solid phase extraction (D-µ-SPE) adsorbents for the extraction of nilotinib coupled with HPLC-UV in a short time of analysis. Experimental parameters affecting extraction efficacy such as adsorbent amount, ionic strength, pH value, adsorption-desorption time and type of elution solvent, were optimized.

Results: Under optimal experimental conditions, the linear dynamic was achieved in the range of 0.25-5.00 µg/mL in human plasma and 0.01-0.20 µg/mL in wastewater. The extraction recovery was in the range of 89.18-91.53% and 94.39-99.60% for nilotinib and MIL-101(Fe) and also 91.22-97.35% and 98.14-100.78% for nilotinib and MIL-53(Al) from human plasma and wastewater respectively.

Conclusion: HPLC-UV determination of nilotinib after the D-µ-SPE method showed acceptable accuracy and precision in both plasma and wastewater. In comparison between the two adsorbents, the extraction procedure was easier and faster with MIL-53(Al) as the adsorbent.

Background: The Ferluago W.D.J. Koch genus includes 48 accepted perennial herbs that are distributed in the Mediterranean region, Southeast Europe, Central and Middle East of Asia. These plants are widely used in folk and conventional medicine due to their biological benefits such as anti-microbial, anti-inflammatory, anti-cancer, and immunomodulatory properties. Conducting a comprehensive review based on the structure activity relationships (SARs) of the coumarins, which has not been previously documented, can lead to a better insight into the genus Ferulago and its beneficial therapeutic activities.

Methods: This review covers literature from 1969 to 2023, were collected from various scientific electronic databases to review phytochemical, pharmacological, and ethnopharmacological data of Ferulago species, as well as latest information on the SAR of reported coumarins from this genus.

Results: Phytochemical studies showed that the biological actions of this genus are mediated by the reported specialized metabolites, such as coumarins and flavonoids. Simple coumarins, prenylated coumarins, furanocoumarins, and pyranocoumarins are the largest subclasses of coumarins found in diverse Ferulago species, which have discussed the biological effects of them with a focus on the Structure-Activity Relationship (SAR). For example, prenylated coumarins have shown potential leishmanicidal and anti-neuropsychiatric effects when substituted with a prenyl group at the 7-hydroxy, as well as the C₆ and C₈ positions in their scaffold. Similarly, furanocoumarins exhibit varied biological activities such as anti-inflammatory, anti-proliferative, and anti-convulsant effects. Modifying substitutions at the C₅ and C₆ positions in furanocoumarins can enhance these activities.

Conclusion: This study conducted a comprehensive review of all available information on the phytochemical and pharmacological characteristics of Ferulago species. Given the high occurrence of coumarins in this genus, which exhibit potential anti-Alzheimer and anti-microbial properties, it presents promising new therapeutic avenues for addressing these common issues. Further investigation is needed to understand the molecular-level mechanisms of action and to explore their clinical applications.

Background

Obesity has emerged as a major health challenge globally in the last two decades. Dysregulated fatty acid metabolism and de novo lipogenesis are prime causes for obesity development which ultimately trigger other co-morbid pathological conditions thereby risking life longevity. Fatty acid metabolism and de novo lipogenesis involve several biochemical steps both in cytosol and mitochondria. Reportedly, the high catalytically active mitochondrial carbonic anhydrases (CAVA/CAVB) regulate the intercellular depot of bicarbonate ions and catalyze the rapid carboxylation of pyruvate and acetyl-co-A to acetyl-co-A and malonate respectively, which are the precursors of fatty acid synthesis and lipogenesis. Several in vitro and in vivo investigations indicate inhibition of mitochondrial carbonic anhydrase isoforms interfere in the functioning of pyruvate, fatty acid and succinate pathways. Targeting of mitochondrial carbonic anhydrase isoforms (CAVA/CAVB) could thereby modulate gluconeogenetic as well as lipogenetic pathways and pave way for designing of novel leads in the development pipeline of anti-obesity medications.

Methods

The present review unveils a diverse chemical space including synthetic sulphonamides, sulphamates, sulfamides and many natural bioactive molecules which selectively inhibit the mitochondrial isoform CAVA/CAVB with an emphasis on major state-of-art drug design strategies.

Results

More than 60% similarity in the structural framework of the carbonic anhydrase isoforms has converged the drug design methods towards the development of isoform selective chemotypes. While the benzene sulphonamide derivatives selectively inhibit CAVA/CAVB in low nanomolar ranges depending on the substitutions on the phenyl ring, the sulpamates and sulpamides potently inhibit CAVB. The virtual screening and drug repurposing methods have also explored many non-sulphonamide chemical scaffolds which can potently inhibit CAVA.

Conclusion

The review could pave way for the development of novel and effective anti-obesity drugs which can modulate the energy metabolism.

Graphical abstract

Objectives

Tobacco smoking is a worldwide health problem and one of the leading causes of premature deaths in last years. As there are lots of researches focusing on cessation strategies with attention to pharmacotherapy and behavioral counseling, the aim of this study was to compare two of the first-line FDA-approved pharmacotherapies for smoking cessation; varenicline and bupropion.

Evidence acqusition

This writing is an overview of researches published in Pubmed database from 2012 to 2022 with “Varenicline” and “Bupropion” as key words. Among the researches that were found, 24 articles were selected which mainly focused on comparison of these two medicines.

Results

Varenicline and bupropion are known as non-nicotinic pharmacotherapy and have been used in addition to nicotine replacement therapy for smoking cessation. Varenicline is partial agonist for α4β2 nicotinic acetyl choline receptors while bupropion, classified as an atypical antidepressant, is actually a norepinephrine and dopamine reuptake inhibitor. Although these treatments can result in some adverse effects including nausea, insomnia, anxiety, irritability, fatigue and abnormal dreams, their efficacy in reduction of craving and also maintenance of abstinence is well been studied and approved by FDA. Moreover, adverse effects are usually mild to moderate clinical symptoms which can be tolerated and also easily managed and prevented in cases.

Conclusion

The efficacy and tolerability of varenicline and bupropion as treatments for smoking cessation is well understood. However, studies have shown that varenicline seems to be more effective in maintaining of abstinence and also reducing craving than bupropion and NRT.

Purpose: To prepare freeze-dried bupivacaine lipospheres intended for topical application in burn injuries. The aim was improving the storage stability and developing a prolonged release pattern to tackle the adverse reactions resulting from the frequent administration of bupivacaine.

Methods: The lipospheres were prepared by hot-melt dispersion method employing bupivacaine base at 1.5 and 3%w/w, tristearin 6% w/w as the core while dipalmitoyl phosphatidylcholine (DPPC) and soy phosphatidylcholine (SPC) as the coat at 0.75, 1.5 and 3% w/w. The lotion was then freeze-dried and cryoprotected by sucrose 3% w/w. Evaluation was carried out through loading and release analysis, storage study, particle characterization including morphology, zeta potential and particle size as well as anti-microbial assessment.

Results: The highest loading, (87.6 ± 0.1%), was achieved using bupivacaine 3% and SPC 0.75%. After 6 months of storage at 4 ͦC, the loading in the lotion and the freeze-dried samples were 17.4 ± 0.2 and 87.2 ± 0.3%, respectively. In vitro dissolution test demonstrated 94.5% and 95% of bupivacaine release from lotion and freeze-dried samples, after 24 h. The respective zeta potential of -1.30 and 26 mV was recorded for lotion and solid-state bupivacaine. Micromeritic evaluation of freeze-dried powder exhibited particle size of 35.23 ± 2.02 μm and highly-wrinkled-irregular morphology without detectable needle structures related to drug free crystals. The powder had rapid reconstitution property and antibacterial activity.

Conclusion: Freeze- drying holds a promising potential to improve the storage stability of bupivacaine lipospheres with well- preserved release pattern and particle properties for further topical application.