Journal of Pharmaceutical Innovation最新文献

The development of smart textiles and materials based on nanofibers has made tremendous progress in integrating natural and synthetic fibers into biomedical applications. An effective method for creating nanofibers with desired qualities, including high surface area, porosity, and mechanical strength qualities that make them appropriate for use in wound healing and medication delivery systems, is electrospinning. In this study, polyvinyl alcohol–silk sericin (PVA–SS) nanofibers loaded with eugenol were successfully fabricated and characterized. SEM analysis confirmed uniform, continuous fibers, while FTIR and DSC demonstrated stable polymer–drug interactions and efficient eugenol encapsulation. The formulation showed favorable physicochemical performance, with a swelling index increasing from 15.8 to 17.7% at 4 °C and remaining stable at 16.1–16.2% at 27 °C, supporting adequate moisture retention for wound healing. Antimicrobial testing showed strong inhibition zones of 17–18 mm (S. aureus) and 19–23 mm (E. coli). Sustained eugenol release was maintained throughout the study period, indicating suitability for reduced dosing frequency. In-vivo evaluation in Wistar rats demonstrated concentration-dependent healing, with 1% eugenol nanofibers achieving 90.45% wound closure by Day 21, compared to 32.44% (0.1%) and 21.58% (control). Histopathology confirmed enhanced epithelialization, collagen deposition, and reduced inflammation. Overall, eugenol-loaded PVA–SS nanofibers exhibit strong antimicrobial activity, effective moisture management, and accelerated tissue regeneration, highlighting their potential as an advanced wound dressing.

Ciprofloxacin HCl orodispersible tablets (ODT) were prepared by direct compression of a mixture of superdisintegrants, fillers, and flow enhancers after proper pre-compression analysis. Post-compression analysis was conducted for content uniformity and disintegration time-based screening of the formulation (disintegration time < 30 s). In vitro (IP type I) and ex-situ (buccal mucosa) analyses were performed in simulated mucosal (pH 7.4) and salivary (pH 6.4) phosphate buffers. Statistical analysis included two-way ANOVA, Pearson’s correlation coefficient (KPC), Student’s t-test, and Bootstrap f2. Pre-compression analysis indicated that flow properties were highly affected by superdisintegrant polymers, in the order of crosspovidone > sodium starch glycolate > croscarmellose sodium, along with talc and magnesium stearate. A similar trend was observed for disintegration time, with formulation F4 showing the shortest disintegration time, followed by F3. In vitro studies revealed that the formulation follows a Makoid-Banakar drug release model, with an initial burst release of 15% in the first 5 min at pH levels of 6.4 and 7.4. In contrast, the Peppas-Sahlin kinetic model fits the release profile in water. Ex-situ permeation studies revealed that F4 exhibited higher permeability and flux than F3 at both pH levels of 6.4 and 7.4, with an approximately 1.3-fold increase. This improvement is likely due to the higher presence of wetting-based superdisintegrants in F4.

Graphical Abstract

In vitro analysis of orodispersible tablets of Ciprofloxacin HCl

Purpose

Cigarette smoking leads to the cause of mortality. Current smoking cessation often fails to prevent cravings. Intranasal drugs offer a rapid alternative, but existing nasal sprays require frequent dosing, affecting patient adherence. We developed sustained-release nicotine-encapsulated chitosan nanoparticles (NHT-loaded CSNPs) to prolong nicotine effects.

Methods

NHT CSNPs were synthesized using ionic gelation. Their size and zeta potential were determined. Stability studies were conducted for 90 days. In vitro release kinetics and cytotoxicity were assessed. Pharmacokinetic properties of the NHT-loaded CSNPs were performed in male Sprague Dawley rats.

Results

The NHT: CS: Sodium Tripolyphosphate (NHT: CS: TPP) ratio of 1:4:4 resulted in the lowest particle size of 120.36 ± 3.23 nm, the zeta potential of 36.06 ± 1.70 mV, the encapsulation efficiency of 96.16 ± 0.76%, and the loading capacity of 29.26 ± 1.09%. The NPs showed sustained release activity. The NHT-loaded CSNPs were stable for 90 days, with fibroblast and Calu-3 cell viability > 50%. In vivo studies revealed a lower area under the curve (AUC) and longer half-life (T½) compared to NHT, indicating safety and sustained release.

Conclusion

In conclusion, the optimized formulation exhibited sustained-release properties with potential use in future smoking cessation research.

Purpose

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of mortality worldwide. Several inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R), the key hepatic cholesterogenic enzyme, are prescribed to treat hypercholesterolemia and ASCVD. Statins, the established HMG-R inhibitors, exhibit promising cholesterol-lowering effects; however, their long-term use has prompted significant concerns, necessitating the search for additional therapeutic candidates with strong HMG-R inhibitory activity. Therefore, this study aims to find potential HMG-R inhibitor/s that may help reduce excess cholesterol levels via targeting HMG-R activity.

Methods

In this study, 1285 FDA-approved small molecules were assessed for their HMG-R inhibitory potential using high-throughput virtual screening (HTVS) and molecular docking simulations (MDS).

Results

Based on lowest binding energies and favourable docking interactions, seven compounds were selected for further studies. These compounds satisfied the Lipinski’s rules, ADME, and toxicity evaluations. Computational molecular informatics analysis revealed that all screened compounds efficiently occupied the catalytic domain of HMG-R, with binding energy (∆G) ranging from − 5.82 to -7.73 kcal/mol. In contrast, amongst other compounds, glipizide showed the lowest ∆G (-7.73 kcal/mol), surpassing the ∆G of the substrate HMG-CoA and standard drug atorvastatin (-3.99 and − 4.22 kcal/mol, respectively). A 100 ns MDS demonstrated that glipizide exhibited better stability compared with atorvastatin. Molecular mechanical-generalized Born surface area (MM-GBSA) analysis further showed that free ∆G of glipizide (-21.59 kcal/mol) was better than that of atorvastatin (-18.05 kcal/mol).

Conclusion

In conclusion, as an FDA-approved antidiabetic drug, glipizide may be used for managing patients with both diabetes and hyperlipidaemia by additionally targeting human HMG-R.

Purpose

>Luteolin, a naturally occurring flavonoid, exhibits potent anticancer activity but is limited by poor aqueous solubility and low oral bioavailability. This study aimed to develop and optimize a niosomal drug delivery system to enhance the solubility, stability, and therapeutic efficacy of luteolin against breast cancer.

Methods

Luteolin-loaded niosomes were prepared using the ethanol injection method and lyophilized with 2.5% mannitol as a cryoprotectant. A Central Composite Design (CCD) was used to optimize formulation variables, including the Span 60: cholesterol molar ratio, lipid concentration, and sonication time. The optimized formulation was evaluated for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, surface morphology (via TEM), drug release behavior, and in vitro cytotoxicity against MCF-7 breast cancer cells.

Results

The optimized niosomal formulation demonstrated a mean particle size of 162.67 ± 2.87 nm, PDI of 0.173 ± 0.01, zeta potential of -34.63 ± 1.07 mV, and entrapment efficiency of 87.07 ± 1.69%. TEM confirmed spherical, nanosized particles. XRD analysis revealed reduced crystallinity of luteolin in the formulation, suggesting improved solubility. The in vitro release study showed sustained drug release over 24 h in both simulated gastric (78.26 ± 3.87%) and intestinal (81.13 ± 2.85%) fluids. Cytotoxicity study showed significantly enhanced cytotoxicity across all tested concentrations for luteolin-loaded niosomes compared to pure luteolin (LUT), indicating improved anti-cancer potential.

Conclusion

The developed luteolin-loaded niosomal formulation significantly improved the physicochemical properties and anticancer efficacy of luteolin. These findings suggest that niosomal encapsulation is a promising strategy for enhancing the oral bioavailability and therapeutic potential of luteolin in breast cancer treatment.

Purpose

Pancreatic ductal adenocarcinoma (PDAC) is the most fatal type of pancreatic cancer and has a very low survival rate. DNA methylation plays a significant role in the development and progression of PDAC. Azacitidine (AZA), a potent hypomethylating agent, has shown therapeutic potential for PDAC, but its clinical efficacy is limited due to its rapid in vivo metabolism and degradation.

Methods

To overcome these limitations associated with AZA, we developed liposomal formulations, encapsulating AZA-copper complex, with improved entrapment and desirable attributes. The resulting liposomes were further tailored with surface modifications, producing polyethylene glycol (PEG) coated liposomes (PEG-Lipo) and CD44 receptor-directed hyaluronic acid-coated liposomes (HA-Lipo). These liposomal formulations were lyophilized using a rationally designed lyophilization process, resulting in stable formulations, which were further confirmed by stability studies.

Results

The physicochemical characterization showed vesicular structure with a size of < 200 nm and optimal drug entrapment (~37–40%). Preclinical pharmacokinetic studies in Wistar rats demonstrated prolonged circulation and increased half-life with surface-coated liposomes as compared to uncoated liposomes (UC-Lipo). In vitro cellular studies using Panc-1 cell lines assessed cytotoxicity, cellular uptake, reactive oxygen species (ROS) generation, and apoptosis. HA-Lipo demonstrated significantly better results (p < 0.0001) than UC-Lipo. Further, in a 3D spheroid model of Panc-1 cells, HA-Lipo showed improved efficacy with spheroid regression (56.32 ± 16.90 μm), compared to PEG-Lipo (77.87 ± 41.52 μm) and UC-Lipo (136.12 ± 79.99 μm).

Conclusion

These results indicate that HA-Lipo loaded with AZA offers a promising strategy for targeted and effective delivery of AZA to PDAC tissues, potentially improving treatment outcomes.

Graphical Abstract

Purpose

Khellin, a major furanochrome found in Ammi visnaga L. (Apiaceae family), has traditional uses in Middle Eastern countries for its diuretic properties and in treating renal colic associated with kidney stones. The purpose of this investigation was to evaluate the anti-urolithiatic activity of Khellin by investigating its diuretic and antioxidant properties.

Methods

In-silico molecular docking studies were used to explore the binding affinity of Khellin with glycolate oxidase. Diuretic effects were tested using the Lipschitz model in Wistar rats, and urinary ion levels of Na+, K+, and Cl − were measured. Ethylene glycol-induced urolithic rats were treated prophylactically and therapeutically with Khellin. At the end of treatment, urinary stone promoters and inhibitors, renal antioxidant markers (Catalase, Superoxide dismutase, reduced Glutathione), liver glycolate oxidase (GO), and Lactate dehydrogenase (LDH) activity, and renal histopathology were evaluated.

Results

Molecular docking revealed a significant binding affinity of Khellin to GO, with a binding energy of -8.4 kcal/mol, surpassing the co-crystallized ligand. Prophylactic treatment of Khellin significantly reduced urinary CaOx markers, increased magnesium and citrate excretion, and improved renal architecture by reducing CaOx crystal deposition. Antioxidant defenses were enhanced by increased Catalase, Superoxide dismutase, and reduced Glutathione levels, with decreased lipid peroxidation. Khellin also modulated GO and LDH activity, preventing CaOx crystal formation.

Conclusion

Khellin demonstrated significant anti-urolithiatic activity by promoting diuresis, modifying glycolate oxidase, and enhancing antioxidant defenses, supporting the traditional use of Ammi visnaga in managing urolithiasis.

Purpose

Metformin hydrochloride (Metformin HCl) is commonly used for the treatment of non-insulin-dependent diabetes. It has low bioavailability and many side effects such as gastric irritation after oral administration. This study aims to formulate new microemulsions containing metformin for transdermal application and to assess their in vitro and in vivo bioavailability.

Methods

Non-ionic surfactants were used to develop seven microemulsions (MEs) containing metformin HCl. The MEs were characterized by their droplet size, polydispersity index, and rheological properties. Furthermore, the flux of metformin was estimated through rat’s skin using Franz diffusion cells. In addition, the oral and transdermal in vivo bioavailability was evaluated in rats.

Results

The results showed that the developed MEs had colloidal properties. In vitro bioavailability using Franz diffusion cells through the skin over 24 h showed a flux as high as 81.78 µg/cm².hr. Moreover, the in vivo transdermal bioavailability of metformin in the developed MEs in rats was slightly higher than the oral solution.

Conclusion

The developed nonionic metformin-loaded microemulsions were found to be ideal carriers and promising formulations for the transdermal administration of metformin HCl.

Purpose

Polysaccharides have been widely known to exhibit various biological effects. This study explored the potential health benefits of polysaccharides extracted from Bergera koenigii leaves (BKLP) as antioxidants, antidiabetic, and antihypertension agents.

Methods

Bergera koeniigi leaves were dried and ground to form a fine powder. The extraction of polysaccharides was conducted by using microwave-deep eutectic solvent-assisted extraction. After extraction, various biological activities, physicochemical, and structural characterizations of polysaccharides were further investigated.

Results

The extraction was optimized using a response surface approach, resulting in a yield of 18.21% at 30% microwave power, 2 min extraction time, 1% DES concentration, 1:20 g/mL solid-to-buffer ratio, and employing DES-BUD (citric acid monohydrate:1,4-butanediol-based deep eutectic solvent). Following optimization, an extensive physicochemical and structural analyses were performed. BKLP showed a low molecular weight (28.14 kDa), highly water-soluble due to its high amorphous, low-methoxy polysaccharide (DE = 21.50%), and exists in β-configuration. It is largely composed of glucose, galactose, and xylose, which are considered glucose-rich polysaccharides. BKLP had a non-triple helix configuration and minimal branching. The biological activities of BKLP revealed high dose-dependent antioxidant, antidiabetic, and antihypertensive properties. BKLP demonstrated DPPH, ABTS, and FRAP activity, exhibiting IC₅₀ values of 0.53 mg/mL, 0.27 mg/mL, and 1.23 mM FeSO₄ at 1 mg/mL, respectively. BKLP also inhibited α-amylase and Angiotensin-converting enzyme (ACE), with IC₅₀ values of 0.62 mg/mL and 0.70 mg/mL.

Conclusion

BKLP has been shown to exhibit strong antioxidants, antidiabetic, and antihypertensive activities, which potentially could be applied as a natural health benefit for diabetes and hypertension management.