Future Journal of Pharmaceutical Sciences最新文献

Background

Skin integrity is crucial for human body normal physiological homeostasis. Skin wound management is critical to prevent progressive infection, scarring, and many other problems that could develop if wounds are not optimally treated. In this work, hyaluronic acid-coated silver nanoparticles loaded with vancomycin were evaluated as a potent comprehensive system to cure and inhibit infections of skin wounds.

Results

In vitro testing of the prepared silver nanoparticles was carried out, assaying its particle size, polydispersity index, zeta potential, and UV absorbance. Silver nanoparticles were optimized by applying two-factor three-level full factorial design utilizing Design-Expert® software. The optimum system showed particle size 399.71 nm ± 8.4, − 60.31 mV ± 4.6 for zeta potential, and 3.74 silver UV absorbance. In vivo study on surgically induced wounds in dogs manifested that the optimum drug-loaded system significantly boosted the wound healing process compared to plain system, drug solution, or control group providing rapid and complete skin regeneration. This was evidenced by clinical observations which showed significantly higher percent wound contraction and complete epithelization. Also, histopathological examinations revealed organized collagen deposition in well-formed granulation tissue in the optimum drug-loaded system. Biochemical, and gene expression analysis showed significant up-regulation of growth factor-related markers namely; VEGF and TGF-ß, and immune-related markers specifically; CCR4 and CD4 + .

Conclusions

Thus, hyaluronic acid-coated silver nanoparticles loaded with vancomycin offer a very auspicious system for skin wound healing purposes.

Graphical abstract

Meropenem is frequently employed empirically to treat both single and polymicrobial infections. In clinical practice, meropenem injections have been shown to induce thrombocytopenia. The main aim of this study was to examine the incidence of thrombocytopenia following administration of a standardized dose of meropenem. This cross-sectional observational study was conducted at a tertiary care hospital from January 1, 2022, to July 15, 2022. This study included 210 patients admitted to intensive care unit. The patient received a typical dose of meropenem depending on age (300–2000 mg) and had no prior medical history of blood dyscrasias. Thrombocytopenia was observed in 59.5% of subjects who were administered a standard dose of meropenem. Absolute thrombocytopenia was noted in 24.7% of the patients, whereas relative thrombocytopenia was detected in 34.8%. Additionally, 41.5% of the participating patients exhibited no alteration in platelet count. Statistical analysis revealed no significant association between sex and meropenem-associated thrombocytopenia (P = 0.522). Meropenem-induced thrombocytopenia didn’t correlate with age in patients undergoing combination therapy (P = 0.586) or monotherapy (p = 0.615). A significant correlation (p < 0.05) was observed between the dosage (300 mg–3 g) and duration of medication use and thrombocytopenia. The odds ratio indicated an elevated probability of patient fatalities in the single therapy group. This study suggests that thrombocytopenia may arise during meropenem treatment, suggesting that it is a potential adverse effect for physicians and pharmacists to consider during therapy.

Background

Bone tissue regeneration based on the use of porous biomaterial scaffolds is considered a promising approach for treating bone defects and fractures healing. A porous alginate scaffold comprising hydroxyapatite nanoparticles loaded with tranexamic acid was formulated. The prepared scaffolds were characterized in terms of the release profile of tranexamic acid and scanning electron microscopy imaging. A cranial bone defect in rabbits (6 defects/3 rabbits/group) was used as a model for the assessment of hemostatic activity of the used scaffolds and the assessment of the bone formation histomorphometrically after its application for 14 days.

Results

The scaffold appeared with irregular porous structure and controlled the release of tranexamic acid over 4 h. The hemostatic time of the medicated and non-medicated scaffolds were 20 and 60 s, respectively. They were significantly lower than the control group (200 s, p < 0.05). The microscopic examination was done after staining histologically prepared sections from the bone defect with Masson trichrome stain and the area % of the newly developed bone was computed. For the medicated group, the new bone area % (75.8 ± 4.9%) was significantly higher than the non-medicated group (58.1 ± 5.9%, p < 0.001). Both groups were significantly larger than the control group that showed bone area % of 43.1 ± 5.6 (p < 0.05). The histomorphometric analysis showed that the medicated scaffold-treated group had more mineralized newly formed bone tissue and smaller amount of soft tissue and residual materials. In contrast, the non-medicated scaffold showed non-mineralized bone cells with larger soft tissue and residual materials.

Conclusion

These results suggested the promising effect of the tranexamic acid-loaded scaffolds in minimizing the time to reach hemostasis by stabilization of the formed hematoma. Additionally, they could improve the quality (mineralization) and the quantity (amount) of the newly formed bone.

Graphical abstract

Background

The effectiveness of conventional oral antiepileptic drug administration is hampered by issues such as inadequate bioavailability, dose-related adverse effects and non-compliance in alleviating epilepsy. Oral antiepileptic drugs have not been successful in treating epilepsy due to high first-pass metabolism, and restriction due to blood–brain barrier and oxidative damage is a significant problem experienced by epileptic patients taking antiepileptic drugs.

The major goal of the current study was to explore the ability of the developed chitosan-coated nanostructured lipid carriers of Oxcarbazepine (CS OXC-NLC) integrated with Vitamin E to lessen oxidative stress and offers neuroprotection and aids in boosting the antiepileptic efficacy through intranasal drug delivery.

Results

In the present work, CS OXC-NLC was fabricated using melt emulsification process. Central Composite Rotatable Design has been utilized to optimize formulation. The study findings showed that optimized CS OXC-NLC exhibited 1.8 times increment in in vitro release and a twofold enhancement in permeability in comparison with the Oxcarbazepine suspension. Confocal microscopy verified the improvement in penetration by showing greater fluorescence in CS OXC-NLC (40 µm) than Oxcarbazepine suspension (22.8 µm) through the nasal mucosa. The pharmacokinetic parameters and biodistribution of OXC levels in the brain and plasma were duly examined. The rise in the amount of drug inside the brain demonstrates the effectiveness of targeting via intranasal administration.

Conclusion

The study outcome demonstrated that the developed CS OXC-NLC is a viable synergistic method producing alluring results for alleviating epilepsy. It depicts the potential of chitosan coating in enhancing the in vivo prospect of the developed formulation through intranasal delivery. Chitosan plays a significant role in enhancing the performance of NLC for intranasal delivery owing to its mucoadhesion properties, controlled release, permeation enhancement and biocompatibility.

Graphical abstract

Background

This study focuses on a fixed-dose combination of lidocaine hydrochloride and diltiazem hydrochloride for the treatment of anal fissures, where lidocaine acts as an anesthetic and diltiazem serves as a slow calcium channel blocker. The objective is to provide a concise overview of the fundamental principles of spectrophotometric and chromatographic methods for quantitative analysis from 2012 to 2022.

Main text

This review highlights the development of novel techniques for both individual and simultaneous quantification, including ultraviolet–visible spectrophotometry (UV–Vis), high-performance liquid chromatography, and high-performance thin-layer chromatography. Additionally, it addresses the capability of various analytical methods to detect and measure compounds at microgram to nanogram levels.

Conclusions

From 2012 to 2022, significant advancements in spectrophotometric and chromatographic methods for analyzing pharmaceutical compounds such as lidocaine and diltiazem have been made. These advancements have improved the sensitivity, accuracy, and efficiency of quantitative analyses, contributing to better quality control and therapeutic efficacy of pharmaceutical products. Modern techniques can detect and quantify compounds at microgram to nanogram levels, ensuring accurate dosing and safety assessments in pharmaceutical formulations.

Background

Osteoarthritis, the most common joint disease, affects over 500 million people globally, especially the elderly. Due to the increasing aging population and obesity rate, obesity is expected to increase over time, making it a significant public health challenge. This study investigated the protective effects of bitter lemon extract against obesity-exacerbated osteoarthritis.

Methods

Thirty male Wistar rats were randomly grouped into six (n = 5). Group 1(control) received 1 ml/100 g water daily. Groups 2–6 were induced in obesity using a high-fat diet. Groups 3–6 were induced with osteoarthritis using 4 mg/kg sodium monoacetate. Group 4 received 40 mg/kg ibuprofen, while groups 5 and 6 received 100 mg/kg and 200 mg/kg Mormordica charantia (MC), respectively, orally for 18 days.

Results

MC Treatment conferred a marked reversal of the cardinal signs of obesity-linked osteoarthritis, restricted inflammatory markers, such as TNF-α and IL-1β, and adipokines, such as leptin. There is also a possible mechanism for MC cartilage protection by suppressing the collagen-damaging enzyme MMP-13, while reversing the cartilage-building block aggrecan suppression.

Conclusion

Current research suggests that bitter melon extract can serve as an alternative therapy for obesity-related Osteoarthritis. Its multi-target actions on inflammation, oxidative stress, and cartilage degradation may offer advantages over the current treatments that focus on symptom relief.

Background

Targeting lung cancer while sparing healthy cells is the cornerstone of chemotherapy; however, bioavailability issues and complex biological barriers prevent their accumulation in the tumor sites. Working on this rationale, the present study was aimed to develop novel and affordable hybrid nanocarriers combined with folate and pH-responsive functionalities for targeted delivery of Resveratrol (FOL-RSV-LPHNCs).

Methods

The developed FOL-RSV-LPHNCs were first optimized by the design of experiment with Box–Behnken design and then characterized for physicochemical properties, cytotoxicity, in vivo pharmacokinetic behavior and anticancer efficacy in the xenograft mouse model.

Results

Results showed that optimized FOL-RSV-LPHNCs had a monodisperse spherical size of 247.86 ± 0.30 nm, entrapment efficiency of 93.72 ± 0.10% and drug loading of 4.16 ± 0.02%, respectively. The amount of RSV released from FOL-RSV-LPHNCs was 96.53 ± 2.16% at pH 5.8 and 23.21 ± 2.01% at pH 7.4, indicative of a pH-responsive release pattern and good physiological stability. In vitro cytotoxicity study revealed that FOL-RSV-LPHNCs remarkably inhibited the viability of A549 cells and produced negligible toxic effect on Wi-38 healthy cells. The single-dose intravenous administration of FOL-RSV-LPHNCs displayed 3.79-fold longer AUC_0-∞, 3.54-fold greater t_1/2 and 4.16-fold higher MRT_0-∞ than free RSV. Finally, in vivo targeting and anticancer studies demonstrated that FOL-RSV-LPHNCs selectively internalized to the cancerous region and suppressed the tumor volume with an 8.66-fold higher rate in the xenograft mouse model. The folate receptor-mediated uptake mainly facilitates this superior therapeutic response which was further confirmed by in silico molecular docking and dynamic simulation.

Conclusions

Our findings suggested that FOL-RSV-LPHNCs might serve as an auspicious nanoplatform for targeted drug delivery and treatment of lung cancer.

Graphical Abstract

Globally, hepatocellular carcinoma (HCC) presents a clinical and financial burden, as it is often diagnosed at a later stage. Cisplatin is one of the most commonly used chemotherapeutics for treating various types of solid tumours; however, it is a double-edged sword due to its cytotoxic effects. Consequently, we hypothesized that combining cisplatin with melatonin could be effective in treating HCC. Additionally, melatonin may mitigate the severe adverse effects of cisplatin on normal cells through its cellular protection, immunomodulation, and antioxidant activities. Forty male adult Wistar rats were randomly divided into five groups: Group 1(n = 8), negative control group. HCC was induced in 32 rats with diethyl nitrosamine and carbon tetrachloride injection. Following induction, rats were divided into group 2 (HCC): diseased control; group 3 (HCC-Cis): HCC rats received cisplatin (2.5 mg/kg I.P. once every week for 3 weeks); group 4 (HCC-Melatonin): HCC rats received melatonin in drinking water (20 mg/L for 3 weeks); and group 5 (HCC-Cis-Melatonin; Combined therapy): the HCC rats received both cisplatin and melatonin. HCC group revealed significant elevation in ALT, AST, and AFP associated with increased TNF-α and MDA levels. Hepatic tissue exhibited a significant increase in VEGF, MDM2, COX-2, and miR-155, and a decrease in caspase-3 associated with hepatic damage, ballooning of hepatocytes, and increased BCL-2 and CD68 immunostaining. Although cisplatin was able to induce HCC apoptosis by COX-2 and MDM2/p53/ miR-155 modulation, it aggravated normal hepatocytic damage that was improved by the antioxidant and anti-inflammatory effects of melatonin. In conclusion, melatonin and cisplatin co-administration may be a viable strategy to preserve liver function by shielding healthy hepatocytes from the cytotoxic effects of cisplatin.

Background

Over the past centuries, Aloe species have been traditionally used in managements of infectious ailments. However, no scientific investigation has been conducted into their mechanistic actions behind their antimicrobial activities. The main purpose of this study is to investigate the anti-virulence activities of Aloe marlothii A. Berger (AM) and Aloe striata Haw (AS) leaves and roots against Pseudomonas aeruginosa based on biofilm, pyocyanin and motility assays. Besides, the metabolic profiling of their different organs was evaluated via HPLC–MS/MS analysis. A molecular docking study of marker compounds into a LasR target was conducted to gain an insight into the bioactive metabolites involved into mechanism of action.

Results

A. marlothii roots (AMR) and A. striata leaves (ASL) displayed significant activity against P. aeruginosa at 0.5 MIC via decreasing the biofilm development, pyocyanin production, swarming and swimming motilities. HPLC–MS/MS analysis led to the identification of one hundred metabolites belonging to different chemical classes. Additionally, it revealed the richness of AMR and ASL with anthraquinones and anthrones. Molecular docking of tentatively identified anthraquinones and anthrones was performed, revealing that chrysophanol-8-O-glucoside and 6-malonylnataloin revealed superior binding affinities and stabilities within the pocket of LasR system, compared to TP-4.

Conclusions

These findings give sound evidence for the use of AMR and ASL as effective anti-virulence agents against P. aeruginosa.

Background

Interest in using phytochemicals and herbal medicines to treat skin conditions like acne vulgaris has grown steadily over the last few decades and is described as a chronic inflammatory condition of the pilosebaceous unit that affects teenagers and young adults. Its treatment emphasizes the four main factors that contribute to its development: inflammation, excessive growth of Cutibacterium acne, hyperkeratinization, and sebum production.

Main body

Topical retinoids, oral isotretinoin, benzoyl peroxide, and antibiotics are all part of the treatment. Herbal medicine is a potential complementary and alternative medicine approach in this respect. Additionally, this review gives a full picture concerning acne pathogenesis, molecular targets for acne treatment, antibiotic resistance and existing medications and their pros and cons, herbal skincare products, and bioactive plant chemicals.

Short conclusion

This comprehensive study offers proof that phytochemicals and medicinal plants act as promising therapies for mild to moderate acne vulgaris through shed light on medicinal plants that have a long history of use and have been shown to possess low adverse effects. These plants are a reliable source for the preparation of new drugs. However, to substantiate their efficacy and safety claims, higher-quality research and clinical trials are required.