DARU Journal of Pharmaceutical Sciences最新文献

Objectives: Fruit vinegar is one of the most famous fruit byproducts worldwide with several unique properties. There are two types of fruit vinegar, artisanal and industrial, for consumers to choose from. This review aims to assess for the first time the phytochemistry of fruit vinegar and its anti-inflammatory effects.

Method: The present work was conducted based on a literature search that selected the relevant papers from indexed databases such as Scopus, Science Direct, MDPI, PubMed, Hindawi, and Web of Science. We used numerous terms to assure a good search in different databases, including fruit vinegar, phytochemistry, bioavailability and bioaccessibility, and anti-inflammatory effect. All articles were selected based on their relevance, quality, and problematic treatment.

Results: Literature data have shown that vinegar has a long medicinal history and has been widely used by different civilizations, due to its richness in bioactive molecules, vinegar plays an important role in the prevention and treatment of various inflammatory diseases, including atopic dermatitis, mastitis, asthma, arthritis, acute pancreatitis, and colitis. Fruit vinegar consumption benefit is highly dependent on its chemical composition, especially organic acids and antioxidants, which can act as nutraceuticals.

Conclusion: Fruit vinegar has a rich chemical composition, including organic acids that can be transformed in the digestive system into compounds that play an important role in health-promoting features such as anti-inflammatory effects throughout the control of intestinal microbiota and pro-inflammatory cytokine production.

Background

Aberrant expression of histone deacetylases (HDACs) and ribonucleotide reductase (RR) enzymes are commonly observed in various cancers. Researchers are focusing on these enzymes in cancer studies with the aim of developing effective chemotherapeutic drugs for cancer treatment. Targeting both HDAC and RR simultaneously with a dual HDAC/RR inhibitor has exhibited enhanced effectiveness compared to monotherapy in cancer treatment, making it a promising strategy.

Objectives

The objective of the study is to synthesize and assess the anti-cancer properties of a 1,10-phenanthroline-based hydroxamate derivative, characterizing it as a novel dual HDAC/RR inhibitor.

Methods

The N¹-hydroxy-N⁸-(1,10-phenanthrolin-5-yl)octanediamide (PA), a 1,10-phenanthroline-based hydroxamate derivative, was synthesized and structurally characterized. The compound was subjected to in vitro assessments of its anti-cancer, HDAC, and RR inhibitory activities. In silico docking and molecular dynamics simulations were further studied to explore its interactions with HDACs and RRM2.

Results

The structurally confirmed PA exhibited antiproliferative activity in SiHa cells with an IC₅₀ of 16.43 μM. It displayed potent inhibitory activity against HDAC and RR with IC₅₀ values of 10.80 μM and 9.34 μM, respectively. Co-inhibition of HDAC and RR resulted in apoptosis-induced cell death in SiHa cells, mediated by the accumulation of reactive oxygen species (ROS). In silico docking studies demonstrated that PA can effectively bind to the active sites of HDAC isoforms and RRM2. Furthermore, PA demonstrated a more favorable interaction with HDAC7, displaying a docking score of -9.633 kcal/mol, as compared to the standard HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), which exhibited a docking score of -8.244 kcal/mol against HDAC7.

Conclusion

The present study emphasizes the prospect of designing a potential 1,10-phenanthroline hydroxamic acid derivative as a novel dual HDAC and RR-inhibiting anti-cancer molecule.

Graphical Abstract

Background

Pembrolizumab has been widely used in patients since its release, but information on cardiac Adverse Events (AEs) related to pembrolizumab remains lacking, particularly in Japanese populations.

Objectives

This study aims to evaluate time to onset, incidence rates, and outcomes for pembrolizumab-induced cardiac AEs in patients with cancer using the Japanese Adverse Drug Event Report database.

Methods

We analysed data for the period from April 2004 to March 2022. Data on cardiac AEs were extracted and relative risks of AEs were estimated using the reporting odds ratio.

Results

We analysed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab. Of these, 399 cardiac AEs were associated with pembrolizumab. Signals were detected for six cardiac AEs: myocarditis, immune-mediated myocarditis, pericardial effusion, cardiac tamponade, pericarditis, and pericarditis malignant. A histogram of median times to onset showed occurrence from 33 (21–97) days for immune-mediated myocarditis to 138 (67–168) days for pericarditis malignant, but some cases occurred even more than 1 year after the start of administration. Among these, myocarditis was the most frequently reported (27.1%), with fatal cases also reported.

Conclusion

This study focused on cardiac AEs caused by pembrolizumab as post-marketing AEs. Patients should be monitored not only at the time of administration, but also over time for signs of these AEs, especially myocarditis, as some patients may have serious outcomes.

Graphical abstract

Purpose

A pharmacopoeia is a compendium of guidelines and criteria for drug quality. It was established by a national or regional entity and has legal significance. This applies to administration of drugs in a particular nation or region.

Method

In this study, the differences and similarities of microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations in 14 national and international pharmacopeias were investigated.

Results

It was found that 12 pharmacopeias have given separate microbial limits for total aerobic microbial count (TAMC) and total yeast and mold count (TYMC), and a list of specified microorganisms for which acceptance criteria are defined. However, similarities were noticed in Ph.Eur, Ph. Helv and, BP. Salmonella, and Escherichia coli are the most common pathogens specified for herbal preparations in which boiling water is added prior to use and for internal use in all Pharmacopoeias because they serve as indicators of potential contamination.

Conclusion

From this study, it can be concluded that the differences in microbial limit tests and their acceptance criteria as specified in the various pharmacopoeias need to be harmonized. It will become a more convenient option for global drug manufacturers to import/export herbal drugs, and this would also eliminate the burden of performing various analytical methods and comply with different microbial acceptance criteria set by various pharmacopoeias. The comparative data obtained from this study will be used to develop strategies for revisions of pharmacopoeias in a harmonized manner with respect to microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations.

Background

This study aims to develop an AI-based prediction model for injection drugs that cause anaphylactic shock using Japanese Real-World Data (JADER database) and chemical structure-based analysis.

Methods

Data sourced from the JADER database included adverse drug reaction reports from April 2004 to December 2020. Only drugs with an adverse reaction named "anaphylactic shock" were selected for analysis. For model building, various models were constructed to predict anaphylactic shock-inducing drugs, such as logistic regression, LASSO, XGBoost, RF, SVM, and NNW. These models used chemical properties and structural similarities as feature variables. Dimension reduction was applied using principal component analysis. The dataset was split into training (80%) and validation (20%) sets. Six different models were trained and optimized through fivefold cross-validation.

Results

From April 2004 to December 2020, 947 drugs with the adverse reaction name "anaphylactic shock" were extracted from the JADER database. 320 drugs were excluded due to analytical challenges, and another 400 were removed due to their administration route. 227 drugs were finalized as target medicines. For model validation, the performance of each model was evaluated based on metrics like AUCs of ROC curve, sensitivity, and specificity. Additionally, two ensemble models, constructed from the six models were assessed using bootstrap sampling. Interestingly, it was identified that mepivacaine structural similarity had the highest importance in the final model.

Conclusions

The study successfully developed an AI-based prediction model for anaphylactic shock inducing-injection drugs. The model would offer potential for drug safety evaluation and anaphylactic shock risk assessment.

Graphical abstract

Background

Increased intraocular pressure is a common symptom of glaucoma. In severe circumstances, it may result in loss of eyesight. Glaucoma treatment is difficult due to ocular physiological barriers that prevent medications from reaching the afflicted area. Traditional formulations (eye drops) have a short residence period and are rapidly drained away via the nasolacrimal duct, resulting in increased adverse drug responses and lower efficacy. The usage of nanoparticles such as niosomes could be one potential answer to these problems. While niosomes improve drug penetration, they have little effect on ocular retention of the medication. Contact lenses containing niosomes can assist to overcome this disadvantage.

Objective

This study aims to prepare and evaluate Brimonidine niosomes laden contact lenses for the treatment of Glaucoma.

Methods

Brimonidine niosomes were prepared using thin film hydration method and evaluated. The contact lenses were soaked in the niosomal formulation at varying intervals (3–10 days). Thereafter, the contact lenses were evaluated for %transmittance, %swelling index, drug quantification and in vitro drug release. The pharmacodynamic studies were conducted to assess the reduction in intraocular pressure (IOP) in albino rabbits. The research compared the results of the reduction in intraocular pressure caused by Brimonidine niosomes laden contact lenses with a marketed preparation of niosomes.

Results

Higher concentration of the drug was loaded in contact lenses loaded with Brimonidine niosomes compared to the marketed formulation, by soaking method. The contact lenses exhibited an optimal %transmittance of 98.02 ± 0.36 and %swelling index of 50.35 ± 0.57. Increase in the soaking time up to 7 days led to an increase in the drug concentration in the contact lenses. However, no further increase was observed after the 7th day due to saturation of the contact lenses. Brimonidine niosomes laden contact lenses provided a reduction in intraocular pressure that was similar to the marketed preparation. Further, the contact lenses provided extended release up to 20 h.

Conclusion

Brimonidine niosomes laden contact lenses exhibited superior drug loading through the soaking method, displaying optimal %transmittance and %swelling index. Soaking for 7 days increased drug concentration in contact lenses with no further increase due to saturation. These lenses reduced intraocular pressure like the marketed formulation, offering extended release for 20 h.

Graphical abstract

Abstract

Objective

The efficient inhibition of bacteria and their by-products from infected root canals is hampered by the limitations of traditional root canal disinfection strategies, bacterial resistance to antibiotic drugs, and regenerative endodontics. Polymeric nanoparticles nanocarrier for controlling antibiotic drug delivery were used to overcome the limitations encountered in endodontics treatment.

Background

Several polymeric nanoparticles have been used for the delivery of ciprofloxacin drug. The application of poly (ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles has highlighted the clean and safe delivery of ciprofloxacin (CIP) hydrophilic drug for endodontics treatment. PEG/PLGA was prepared using the solid/oil/water method and the CIP was loaded into polymeric nanoparticles via an ion pairing agent.

Results

The CIP-loaded PEG-PLGA nanoparticles have a spherical shape with a 120 ± 0.43 nm size, the CIP encapsulating efficiency was 63.26 ± 9.24% with a loading content of 7.75 ± 1.13%, and sustained release was achieved over 168 h which followed Higuchi model with a non-Fickian mechanism. Moreover, CIP-loaded PEG-PLGA had low cytotoxicity to the stem cells of the apical papilla.

Conclusion

The results conclude invigorating future perspectives of polymeric nanoparticles for a wide range of drug delivery for various disease treatments. It’s anticipated that these polymeric nanoparticles may divert new expectations in the future for topical antibiotic drug delivery with discrete intracellular medicament, and a safe and clean environment.

Graphical abstract

Background

Alzheimer’s disease (AD) is a neurological disease that causes memory loss over time. Current therapies are limited and frequently inadequate. Epigallocatechin gallate (EGCG), has antioxidant, anti-inflammatory, antifibrosis, anti-remodeling and tissue-protective qualities that may be effective in treatment of different diseases, including AD. Because of nanoparticles’ high surface area, they can enhance solubility, stability, pharmacokinetics and biodistribution, and diminish toxicities. Besides, lipid nanoparticles have a high binding affinity that can enhance the rate of drug transport across BBB. So, EGCG nanoparticles represent a promising treatment for AD.

Objectives

This systematic review sought to assess the efficacy of EGCG nanoparticles against AD in rat/mouse models.

Methods

Study was conducted in accordance with PRISMA guidelines, and the protocol was registered in PROSPERO. Electronic databases were searched to discover relevant studies published up to October 2022.

Results

Two studies met the inclusion criteria out of 1338 and were included in this systematic review. Collectively, the results indicate that EGCG has a significant potential for reducing AD pathology and improving cognitive deficits in rat/mouse models. The formulated particles were in the nanometer range, as indicated by TEM, with good particle size control and stability. EGCG nanoparticles showed superior pharmacokinetic characteristics and improved blood-brain barrier permeability, and increased brain bioavailability compared to free EGCG. Additionally, nanoEGCG were more effective in modulating oxidative stress than free formulation and decreased AChE in the cortex and hippocampus of AlCl3-treated rats.

Conclusion

This systematic analysis of the two studies included showed that EGCG nanoparticles are efficacious as a potential therapeutic intervention for AD in rat/mouse models. However, limited number of studies found indicates insufficient data in this research point that requires further investigation by experimental studies.

Graphical abstract