Future Journal of Pharmaceutical Sciences最新文献

Background

The CDSCO of India has authorized a combination of metformin hydrochloride, teneligliptin hydrochloride, and pioglitazone hydrochloride for the treatment of insulin-independent diabetes. For the purpose of estimating metformin, teneligliptin, and pioglitazone combinations as well as individual commercial formulations, there are a plethora of publicly accessible chromatographic techniques. More importantly, the development of these chromatographic procedures has included the use of chemical solvents that are dangerous to both animals and the environment.

Objectives

However, to date, there has been no documented chromatographic technique that can concomitantly estimate various commercial formulations of drugs under study employing a uniform chromatographic condition and environmentally friendly solvents. In order to concomitantly estimate drugs under study utilizing unified chromatographic conditions, a green HPTLC method was developed.

Method

The AQbD approach was used to carry out the method development. To determine the most important method parameters and response variables, the analytical risk assessment was conducted using the risk priority number ranking and screening approach. Critical method parameters and response variables were modeled using the response surface modeling approach, which relies on the central composite design. Optimal ranges for the intended method operable design region were determined, and control strategy was framed. The chromatographic separation was carried out on preparative TLC plate precoated with silica gel G-60 F₂₅₄ using 1.0%W/V ammonium acetate in ethanol: water: triethylamine (6.5:0.4:0.6, V/V) as mobile phase. The detection of the anti-diabetic drugs under study was carried out at 267 nm wavelength.

Results

The linearity of metformin, teneligliptin, and pioglitazone was found to be 5000–25000 ng/band, 200–1000 ng/band, and 150–750 ng/band, respectively. The %RSD for robustness and precision study was found to be less than 2.0%. The %recovery of method was found to be 98–102%. The assay results were shown to be in compliance with respective labeled claims of anti-diabetic medications when the suggested method was used for concurrent analysis of several formulations and combinations of drugs under study.

Conclusion

The suggested technique was evaluated utilizing red–green–blue model scoring tools. The suggested technique was determined to be precise, accurate, rapid, cost-effective, and easy to apply for the estimation of drugs under study.

Background

Patients with chronic kidney disease (CKD) are at risk of developing conditions such as atherosclerosis and inflammation-induced anemia (AI) due to persistent inflammation. Ziltivekimab, an antibody targeting interleukin-6, is being studied for its potential to reduce inflammatory markers in these patients.

Methods

Following PRISMA guidelines, we searched for relevant randomized controlled trials (RCTs) up to August 20, 2023, and analyzed the data using RevMan 5.4 software. The study period spanned from February 18, 2023, to September 23, 2023. We assessed efficacy outcomes such as high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), and both high-density lipoprotein (HDL) and low-density lipoprotein (LDL), as well as safety outcomes, including adverse events (AEs) and infections. Pooled results were calculated using the random effects model and inverse variance method, with mean differences (MD) and risk ratios (RR) presented alongside 95% confidence intervals (CI).

Results

Our review included three RCTs with a total of 473 patients. Compared to the placebo group, patients treated with ziltivekimab showed significantly lower levels of hs-CRP, fibrinogen, and SAA (MD = − 51.64, 95% CI [− 73.73 to − 29.56], P < 0.00001; MD = − 48.23, 95% CI [− 61.73 to − 34.72], P < 0.00001; MD = − 26.34, 95% CI [− 38.63 to − 14.04], P < 0.0001, respectively). There was a notable increase in LDL and HDL levels (MD = 5.92, 95% CI [2.53 to 9.31], P = 0.0006, I² = 0%; MD = − 5.73, 95% CI [3.75 to 7.71], P < 0.00001, I² = 0%, respectively). No significant difference in AEs or infections was observed between the two groups. Meta-regression analysis indicated a significant linear relationship between the dose of ziltivekimab and its  effect on hs-CRP levels.

Conclusion

Ziltivekimab showed promise in significantly lowering inflammatory markers without a significant impact on AEs or infections, positioning it as a valuable treatment option for patients with chronic kidney disease CKD who are susceptible to inflammatory diseases, particularly atherosclerosis and autoimmune conditions.

Background

Curcumin is an age old traditional medicine. Although curcumin has several advantages, its water solubility and bioavailability limit its use as a natural therapeutic agent. Polymeric nano curcumin could be an excellent option to overcome these challenges to augment its therapeutic efficacy. This work aimed to synthesize curcumin-loaded PLGA nanoparticles and assess their angiogenic and antioxidant potential in the zebrafish model.

Results

The double emulsion solvent evaporation process was employed to make curcumin-loaded PLGA nanoparticles. Curcumin showed ~ 28.23 (± 2.49) encapsulation efficacy with an average diameter of PLGA nanoparticles 168.5 (± 2.5) nm and curcumin nanoparticles about 281.6 (± 17.2) nm, respectively. The curcumin nanoparticles showed no developmental toxicity to the zebrafish embryos while reduced toxicity compared to the native curcumin. Further, the curcumin nanoparticles reduced the generation of reactive oxygen species and improved angiogenesis in the model system. All these results confirmed that the nanoparticle has had higher bio-efficacy than that of native curcumin.

Conclusion

This study shows that PLGA curcumin nanoparticles hold an excellent therapeutic promise for wound healing, tissue regeneration and other biomedical applications where angiogenesis and ROS play critical role.

Background

In recent years, antibiotic resistance rates have become a global concern for clinicians to combat the pathogenic bacteria associated with UTIs. The objective of this current paper is to explore the evidence-based use of natural products as an alternative strategy to reduce the recurrence rates among different UTI patient populations such as pregnant women, postmenopause women, and children.

Main body

Commonly used non-antimicrobial products to treat and prevent UTIs include vaginal estrogen, cranberry, probiotics, D-mannose, hyaluronic acid (HA), Chinese herbal medicine, and ascorbic acid. Literature supports the safety and effectiveness of utilizing these products in different UTI patients to a great extent. The strongest recommendation was given to the utilization of vaginal estrogen replacement therapy in postmenopausal females to prevent rUTI.

Conclusion

We believe our research is the first to provide evidence-based clinical practice guidelines and insight into UTI management using non-antimicrobial drugs in different populations. Our findings can guide future research on the reduction of antimicrobial misuse and preventing antimicrobial resistance.

Graphical Abstract

Background

Quercetin has well-proven anticancer potential through various mechanisms, but its applications in drug delivery are limited due to poor biopharmaceutical properties. The present study was aimed to formulate quercetin nanocochleates (QNC) in order to overcome these limitations. QNC formulation was fabricated by a trapping method, optimized and evaluated for various formulation aspects, in vitro cytotoxicity and pharmacokinetic parameters.

Result

Developed nanocochleates possess particle size and encapsulation efficiency of 205.6 ± 2.55 nm and 76.36 ± 0.88%, respectively. In vitro cytotoxicity study performed using MCF-7 cell lines revealed the comparative efficiency of QNC over pure quercetin. Total growth inhibition concentration (TGI) for pure quercetin was 96.73 μg/ml, while for QNC it was 83.29 μg/ml. Pharmacokinetic study results showed improvement in Cmax and AUC after QNC formulation with increased Tmax showing sustained release.

Conclusion

Overall, the developed QNC formulation markedly improved cytotoxic potential and biopharmaceutical aspects.

Background

Lung cancer (LC) remains a predominant global health concern, especially with escalating tobacco-smoking rates. Present study provides computational screening, molecular dynamics, DFT and simulation analysis of phytoconstituents on EGFR receptors (2ITY and W2O), followed by selection of highest docking score phytoconstituents among 45 for further analysis. The formulation was optimized by Central composite design. Nanostructured-lipid carriers were prepared by high-speed homogenization, combining a 1:1 ratio of liquid lipid (Castor oil) and melted solid lipid (glyceryl monostearate) with 4% surfactant (tween 80) in a water phase containing Glycyrrhizin. The resulting mixture underwent high-speed homogenization at 8000 rpm for 40 min, followed by sonication for 15 min to achieve formulation development of GNLC. The anticancer potential of GNLC have been proved by experimental analysis through MTT assay using A549 Cell lines.

Results

Glycyrrhizin was found to possess maximum docking score − 8.863 and − 8.837 on both 2ITY and W2O respectively. The study unveils Glycyrrhizin’s interactions with EGFR pivotal in cancer progression and treatment. Molecular dynamics simulations highlighted the structural and dynamic interactions within a protein–ligand complex, indicating both stability and flexibility characteristics. DFT analysis of Glycyrrhizin revealed its molecular properties, suggesting stability and potential reactivity. Glycyrrhizin loaded nanostructured lipid carriers (GNLC) have been developed and analysed by various parameters like particle size and drug release zeta potential, SEM analysis, and solubility analysis reveals critical insights into their optimization for effective drug delivery. Both GNLC and Doxorubicin (0.78–50 µg/ml) were used for the activity. The anticancer potential at 12.50, 25 and 50 µg/ml pf GNLC was found to be statistically significant and was comparable with that of standard group Doxorubicin. The observed structural transformations in Glycyrrhizin into a lipid matrix indicate potential enhancements in its drug release.

Conclusions

GNLC shows promising anti-cancer potential in lung cancer, further pre-clinical and clinical studies, is crucial to validate its efficacy, safety, and integration into standard therapeutic regimens.

Graphical abstract

Background

Lung cancer remains a leading cancer type, but current chemotherapy is limited by issues including poor drug delivery, toxicity, and resistance. To address these challenges, we developed a novel PLGA-PEG-LHRH (PPL) nanoconjugate system for improved drug delivery. Curcumin, known for its anticancer and P-gp inhibition properties, was co-loaded with bcl2siRNA (bclsR) to inhibit the bcl2 protein, thus overcoming both resistance mechanisms.

Results

The PPL conjugate was successfully synthesized and characterized using FTIR, ¹H NMR, XRD, XPS and BCA assay. Curcumin and bclsR-loaded PLGA nanoemulsions were prepared by double emulsion solvent evaporation method and characterized. The optimized nanoconjugate had size of 179 ± 16 nm, favorable zeta potential, high drug entrapment, and was confirmed via TEM. Controlled release studies indicated 83% drug release within 24 h. In vitro studies revealed significant cytotoxicity against A549 lung cancer cells, with the nanoconjugate showing IC50 of 8.24 µg/mL compared to 21.26 µg/mL for plain curcumin. Enhanced cellular uptake and effective targeting of A549 cells were observed. Molecular analyses demonstrated significant downregulation of MDR1 and Bcl2 RNA and protein expression, highlighting the nanoconjugates' ability to suppress resistance mechanisms. Pharmacokinetic studies in Wistar rats showed superior plasma drug concentrations, half-life, and AUC for the nanoconjugate versus pure drug suspension. Biodistribution studies showed increased drug accumulation in the lungs. In vivo efficacy studies in Balb/c mice demonstrated higher tumor inhibition ratios for CUR-siRNA PPL NPs (66.89%) and CUR-PPL NPs (59.84%) which was further confirmed with TNFα and p53 levels in blood. Histopathological studies showed good healing in the CUR-siRNA PPL NP- and CUR-PPL NP-treated mice compared to suspension.

Conclusion

From the study, it may be concluded that the PPL nanoconjugate system, loaded with curcumin and bcsR, can be potentially effective, multifunctional targeted approach for lung cancer therapy.

Graphical Abstract

Background

As the leading form of non-melanoma skin cancer, basal cell carcinoma (BCC) presents a considerable challenge to healthcare systems, owing to its widespread occurrence. Current treatment options, such as surgical excision, cryotherapy, and localized therapies like imiquimod or 5-fluorouracil, face challenges, especially in designing drug delivery systems that provide prolonged therapeutic effects. This study aims to develop bio-composite polymeric films for localized drug delivery using natural polymers, lignin, and chitosan, to enhance the delivery of the TLR7 agonist imiquimod for BCC treatment.

Results

The optimized biofilms were prepared by adjusting the polymer ratio and drying techniques to achieve a balanced composition for localized imiquimod delivery. FTIR and DSC characterization confirmed successful drug incorporation into the biofilms, while microscopic studies revealed the biofilms homogeneity and fibrous nature. Drug release studies demonstrated pH-dependent kinetics, with higher release rates at neutral pH. The biofilms exhibited slow and sustained drug release, promising prolonged therapeutic effects. Additionally, the biofilms were non-hemolytic, showed significant antioxidant activity, and demonstrated selective cytotoxicity against B16–F10 mouse skin melanoma cells.

Conclusions

This study suggests that lignin-chitosan-based imiquimod-loaded biofilms hold potential as an effective topical treatment for BCC. The biofilm’s ability to provide sustained drug release, along with their biocompatibility and selective cytotoxicity, indicates a promising approach to enhancing BCC therapy.

Graphical abstract

Background

Curcumin (CUR) is a natural polyphenol and one of the key phytoconstituents found in the rhizomes of Curcuma Longa. It exhibits various pharmacological properties, encompassing antioxidant, anticancer effects, antiseptic, and anti-inflammatory, among several others.

A significant drawback of using CUR is its limited bioavailability, which primarily depends on gut microorganisms responsible for converting it into its bioavailable form. Therefore, the contemporary study intended to formulate a novel PLAROsomal vesicular delivery of CUR, i.e., CUR-PLAROsomes employing a design of experiments approach to examine the influence of various process parameters, such as particle size and drug percentage release.

Result

The prepared CUR-PLAROsomes were characterized for their physicochemical properties using various hyphenated tools. The CUR-PLAROsomes exhibited sizes ranging from 40 to 300 nm, and the optimized batch demonstrated a drug entrapment of 86.38 ± 0.22%.

In-vitro anticancer studies were conducted using human colorectal adenocarcinoma cells (COLO320DM) and human breast adenocarcinoma (MCF-7). CUR-PLAROsomes exhibited significant in-vivo anti-inflammatory potential against carrageenan-induced paw edema. CUR-PLAROsomes were more potent against COLO320DM and MCF-7 cell lines, even at lower concentrations, than pure CUR.

Conclusion

Furthermore, based on the observations, it exhibits potential as an anti-inflammatory agent, suggesting that PLAROsomes are an effective vesicular drug delivery system.

Highlights

• Newly introduced PLARosome is a next generation of Liposomes which have gain popularity owing to its better adaptability to overcome leakage problem of vesicular drug delivery system.

• This is the pioneer attempt to prepare Curcumin-loaded PLARosome as an anti-cancer and anti-inflammatory activity.

• Nano size of the PLAROsomes may contribute to enhance the efficacy of Curcumin as a target specific drug delivery system.

• Site specific delivery of phytoconstituents is possible by use of PLAROsomes as a novel drug delivery system.

Graphical abstract

Background

Cancer is one of the leading causes of death worldwide, with breast and cervical cancers being the most common among women. Over 100,000 new cases of breast cancer and 510,000 new cases of cervical cancer are diagnosed annually. This study aimed to develop and evaluate an eco-friendly, low-cost method to synthesize silver nanoparticles using Hylocereus undatus (dragon fruit) peel extract for their anticancer activity.

Results

Silver nanoparticles loaded with Hylocereus undatus fruit peel extract were successfully developed by a green synthesis technique and were optimized by UV–vis spectroscopy. The nanoparticles had an average size of 71.66 nm, a polydispersity index of 0.3754, and a zeta potential of − 38.52, with a spherical shape and 79.5% silver content. Their maximum absorbance was at 448 nm. Further, in vitro anticancer activity via MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay was evaluated and the synthesized nanoparticles displayed IC₅₀ values at 23.51 µg/ml and 23.66 µg/ml against Hela and MDA MB 231 cell lines, respectively. Cytocompatibility studies showed high cell viability (≥ 95%) in L929 mouse fibroblast cells, indicating low toxicity. In silico analyses, including network pharmacology and molecular docking, identified kaempferol and quercetin as key anticancer compounds, with epidermal growth factor receptor (EGFR) (PDB ID: IM17) being the most significant protein target. Docking studies performed by using the Glide module of Schrodinger’s software displayed that kaempferol and quercetin had higher binding affinities for EGFR as compared to the standard drug erlotinib, with MET 769 being a crucial binding site.

Conclusion

Thus, the outcomes suggest that synthesized silver nanoparticles loaded with Hylocereus undatus fruit peel extract could be a potential and promising drug carrier aiding in cancer treatment.