Journal of Pharmaceutical Innovation最新文献

Purpose

Sustained and simultaneous delivery of antibiotics and flavonoids using nanoformulations represents an innovative therapeutic approach against drug-resistant bacteria. In the present study, we encapsulated levofloxacin and baicalin, a plant flavonoid, into chitosan nanoparticles using the ionic gelation technique and investigated the effects of the dual drug-loaded nanoparticles on virulence factors and toxin-producing genes in P. aeruginosa PAO1.

Methods

The physicochemical properties of Bai-Lvx-CsNPs were investigated using various characterization techniques. Furthermore, the effects of Bai-Lvx-CsNPs on P. aeruginosa growth, virulence traits, and toxin-associated genes were assessed.

Results

Characterization of Bai-Lvx-CsNPs revealed that the particles were spherical, with an average size of 69.26 ± 17.8 nm. The release kinetics of baicalin and levofloxacin from Bai-CsNPs and Lvx-CsNPs demonstrated a gradual and sustained release profile. The highest growth inhibitory activity was observed for Bai-Lvx-CsNPs, with a MIC value of 1.56 mg/mL. Furthermore, the MBC value of Bai-Lvx-CsNPs was determined to be 12.5 mg/mL. In addition, cells treated with ½ MIC of dual-loaded nanoparticles exhibited the highest DNA leakage (24.08 ± 0.43 ng/µL). A reduction in LasA protease activity and pyocyanin production to 48.92 ± 5.72% and 13.33 ± 4.57%, respectively, confirmed the efficient effect of Bai-Lvx-CsNPs in suppressing secreted virulence factors. Treatment with the dually encapsulated nanoparticles significantly reduced swarming motility and the metabolic activity of bacterial biofilm to 1.7 ± 1.6% and 19.09 ± 0.33%, respectively. Furthermore, qPCR analysis showed the greatest reduction in the expression level of the toxA and exoS genes in P. aeruginosa PAO1 following treatment with Bai-Lvx-CsNPs, which decreased to 0.37 ± 0.05 and 0.45 ± 0.07 folds, respectively.

Conclusion

Collectively, these findings highlight the promising antivirulence activity of Bai-Lvx-CsNPs against P. aeruginosa PAO1. Bai-Lvx-CsNPs not only inhibit bacterial growth but also effectively suppress multiple virulence traits, highlighting their potential as a novel therapeutic strategy for the management P. aeruginosa infections. Future in vivo studies are warranted to validate their effectiveness and explore their applicability as alternative or adjunctive treatments against this pathogen.

Background

Developing effective topical therapies for inflammation remains a challenge due to the limitations of conventional treatments, including poor bioavailability, instability, and systemic side effects. Here, we present a novel Ipomoea cairica loaded silver nanoparticle (AgNP) nanogel, integrating natural anti-inflammatory phytochemicals with nanotechnology under a Quality by Design (QbD) framework to achieve enhanced stability, targeted delivery, and therapeutic efficacy.

Methods

AgNPs were synthesized using aqueous Ipomoea cairica leaf extract and incorporated into a nanogel by using Carbopol 940 as the gelling agent. The formulation was optimized using Central Composite Design (CCD) for critical factors such as pH, viscosity, and spreadability. Comprehensive characterization included analysis of particle size, zeta potential, PDI, physicochemical properties, in-vitro release, ex-vivo skin permeation, and in-vivo anti-inflammatory efficacy. Histopathological analysis and stability studies further evaluated formulation performance.

Results

Synthesized AgNPs revealed an average particle size of 98 nm and a zeta potential of -30.35 mV with PDI of 0.3. The optimized nanogel exhibited homogeneity, stability, neutral pH (7.21), viscosity of 706 cps, and spreadability of 53.33 g.cm/s, ensuring skin compatibility. In-vitro release study revealed 77.20% sustained drug release, while ex-vivo skin permeation reached 85.95% demonstrating efficient drug penetration. In-vivo studies confirmed significant anti-inflammatory activity, with a 90.14% reduction in carrageenan-induced edema. Histopathological analysis confirmed minimal tissue damage in the nanogel-treated group compared to control. These findings highlight the synergistic effect of plant phytochemicals and nanogel delivery on AgNP stability and anti-inflammatory efficacy.

Conclusion

The optimized Ipomoea cairica-derived AgNP nanogel demonstrated desirable physicochemical properties, sustained release, efficient skin permeation, and significant anti-inflammatory efficacy. Guided by a QbD approach, this nanogel represents a promising and stable topical delivery system for effective inflammation management.

Graphical Abstract

Background

Artificial Intelligence (AI) is becoming a game-changer in pharmaceutical sciences, especially in drug formulation. Traditional methods of formulation often face challenges such as long timelines, high costs, and repeated trial-and-error processes.

Insights

AI offers solutions by using smart algorithms to speed up development, reduce failures, and improve precision. Machine learning techniques, including neural networks, support vector machines, and reinforcement learning, are being used to predict the best excipients, check drug–drug interactions, improve stability, and even suggest personalized dosages. These tools help researchers make better decisions and cut down on unnecessary experiments. Several AI-driven platforms like IBM Watson, Atomwise, and Schrödinger are already supporting drug discovery and formulation. They combine with existing processes to make workflows more reliable and efficient. Still, challenges remain. Issues with the quality and availability of data, limited computing resources, and regulatory concerns can slow down wider adoption. In addition, questions around ethics and the need for AI systems to be transparent and interpretable are important for building trust. Looking ahead, AI has the potential to transform formulation by integrating omics data, monitoring patients in real time, and creating adaptive formulations that respond to individual needs. Collaboration between pharmacists, AI specialists, and regulators will be essential to make this vision a reality.

Conclusion

AI is paving the way toward faster, cheaper, and more tailored drug development. With continued innovation, it is set to play an indispensable role in pharmaceutical formulation and the advancement of personalized medicine.

Background

Lilium Polyphyllum D. Don ex Royle (Himalayan lily) has long been valued in traditional medicine for managing pain, rheumatism, bronchitis, and intermittent fever. Despite its ethnomedicinal relevance, robust scientific evidence supporting its anti-inflammatory and analgesic effects remains limited.

Objectives

This study aims to validate the traditional anti-inflammatory and analgesic uses of L. polyphyllum bulb by characterizing its phytochemical constituents and elucidating the underlying mechanisms of action through integrated in silico, in vitro and in vivo approaches.

Methods

LC-MS/MS and GC-MS analyses were conducted for the most bioactive chloroform (Chl-fr) and ethyl acetate fractions (EtOAc-fr) respectively. Toxicity was assessed via fibroblast viability, brine shrimp lethality, and acute in vivo testing up to 2400 mg/kg, supported by SwissADMET predictions. Anti-inflammatory effects were determined using chemiluminescence and carrageenan-induced paw edema models, while antinociceptive activity was evaluated through acetic acid-induced writhing and hot plate assays. Molecular docking was performed to explore interactions of identified compounds with myeloperoxidase (MPO) and P2X purinergic receptor 7 (P2X7R).

Results

LCMS/MS and GC-MS analyses of Chl-fr and EtOAc-fr identified 55 bioactive compounds, including phenolic acids, glycosides, alkaloids, flavonoids, and fatty acid esters. The Cr. MeOH-Ext and fractions were non-toxic in fibroblast cells, brine shrimp assay, and in vivo up to 2400 mg/kg, with SwissADMET predictions further supporting their safety profile. The in vitro anti-inflammatory results revealed that Chl-fr, EtOAc-fr, and n-Hex-fr exhibited significant inhibition of oxidative burst for whole blood. In carrageenan-induced anti-inflammatory test, significant decrease in paw edema was observed at 50 and 100 mg/kg for Cr. MeOH-Ext and at 100 mg/kg for n-Hex-fr, Chl-fr and EtOAc-fr. In abdominal constriction test, EtOAc-fr at 50 and 100 mg/kg significantly reduced abdominal writhing followed by n-Hex-fr, Cr. MeOH-Ext, and Chl-fr. In hot plate test, the latency time was significantly increased at 100 mg by EtOAc-fr followed by Chl-fr, and n-Hex-fr. Molecular docking analysis revealed that the identified compounds exhibit strong binding affinities with MPO and P2X7R, further supporting their potential anti-inflammatory and antinociceptive mechanisms.

Conclusion

To our knowledge, this study provides the first comprehensive characterization of the phytochemical profiles of chloroform and ethyl acetate fractions of L. polyphyllum bulb, demonstrating significant analgesic and anti-inflammatory potential that scientifically validate the ethnomedicinal applications in pain and inflammation.

Purpose

In this study, we assessed the effectiveness of micelle solutions of essential oil from Origanum onites L. against clinical strains of Acinetobacter baumannii isolated from intensive care units. The monoterpene p-cymene is also evaluated as a promising mediator targeting A. baumannii AbaR and TnpA by using molecular docking analysis.

Methods

Four strains of A. baumannii were molecularly identified; the oil was examined using gas chromatography/mass spectrometry; MIC was determined using the sonicated method; and the inhibitory zones were read using the well agar diffusion method in comparison to colistin. Using AutoDock Vina, a molecular docking analysis was conducted.

Results

Micelle-homogenous solutions of the oil showed low minimum inhibitory concentrations against A. baumannii (Ab OR792201, OR792204, OR792202, and OR792203), ranging from 0.20% to 0.39% v/v. Carvacrol was the major component of O. onites essential oil, accounting for 76.67% of the total, followed by p-cymene at 7.77%. According to the AbaR and TnpA proteins' molecular docking, the ligand was detected in the active site and had conformations that would allow it to create connections. The hydrophobic contacts between the proteins and p-cymene showed that there were eight different hydrophobic interactions between the ligand and TnpA and six between the ligand and AbaR.

Conclusion

The findings of the study indicated that the chemical components of O. onites essential oil had a strong ability to eliminate the highly lethal A. baumannii, which is encouraging. Molecular docking research also demonstrated the potential for interactions between p-cymene and A. baumannii resistance-related proteins.

Purpose

Ebastine, a BCS Class II medication, serves as an antihistamine for treating various allergic reactions. However, its poor aqueous solubility and low oral bioavailability lead to extensive first-pass hepatic metabolism, significantly limiting its therapeutic effectiveness. To address these limitations, the current study aimed to develop and evaluate a nanofiber-based transdermal gel formulation to enhance Ebastine delivery through the skin.

Methods

Ebastine-loaded nanofibers were prepared using the electrospinning method and optimized with a “Box-Behnken experimental design.” The optimized formulation was incorporated into a gel for transdermal application. The formulation was evaluated using Scanning Electron Microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), in vitro drug release performed using a dialysis membrane, and ex vivo permeation tested through goat skin. Additionally, antimicrobial activity against Staphylococcus aureus was evaluated.

Result

The optimized NF5G2 formulation had a uniform diameter of less than 300 nm with a higher drug entrapment efficiency of 95.23%. The cumulative drug release and skin permeation at 12 h were 88.90% and 87.19%, respectively, following the Korsmeyer-Peppas kinetic model. The antimicrobial study showed significant inhibition of S. aureus, a common skin pathogen linked to chronic urticaria.

Conclusion

The developed Ebastine-loaded nanofiber transdermal gel offers improved drug release, high skin permeability, and effective antimicrobial action. This formulation presents a novel and efficient strategy for treating allergic conditions, paving the way for future applications of nanofiber-based therapies in dermatological care.

Graphical Abstract

Purpose

This study explores emerging digital innovations in pharmaceutical manufacturing, as well as the opportunities and challenges they present for product quality and batch release. A secondary objective was to discuss the regulatory compliance of these digital innovations.

Method

A comprehensive systematised literature review was performed using Web of Science, PubMed, and Scopus research databases. Screening of the identified studies was performed using Covidence online software. The Mixed Methods Appraisal Tool (MMAT) was adapted for the risk of bias assessment.

Results

38 studies were included after screening and risk of bias assessment. The thematic analysis identified 5 empirical themes: ‘PAT and RTRT’ ‘AI’, ‘Process Modelling’ ‘IoT’, and ‘Data Management’. The main opportunities identified included prediction of product quality and variability, deviation root cause analysis, real-time process monitoring, and adaptive control to prevent out of specification products. This study didn’t identify any regulatory challenges to these technologies, however challenges included a lack of personnel with the required technical expertise, data security risks, validation challenges, and potential for inaccuracy.

Conclusions

Emerging digital technologies are being used to support pharmaceutical quality. A review of current guidance did not uncover any regulatory obstacles to theimplementation of the identified technologies, once part of the registered manufacturing process. More opportunities than challenges were identified in the literature. Based on this study, we propose a responsible strategy for future digital innovation implementation and conclude that there is value in (1) Adopting digital innovations in pharmaceutical manufacturing and (2) Supporting digital education for QPs and other quality professionals in pharmaceutical manufacturing.

Objective

This study aimed to develop and optimize a thermosensitive in-situ nasal gel of teriflunomide for effective CNS targeting in the treatment of multiple sclerosis.

Methods

A 2³ factorial design was employed to investigate the effects of Poloxamer 407 concentration, HPMC K4M concentration, and stirring speed on gelation temperature, viscosity, mucoadhesive strength, and drug release. The optimized gel was evaluated for clarity, pH, drug content, spreadability, and in vitro drug release.

Results

The optimized formulation exhibited a pH of 6.12 ± 0.04, a gelation temperature of 32.1 ± 0.3 °C, a viscosity of 3925 ± 112 cps, and a mucoadhesive strength of 1385 ± 27 dynes/cm². Drug content was 99.28 ± 1.14%, and in vitro release showed 98.52% drug release over 24 h, following Higuchi diffusion-controlled kinetics.

Conclusion

The developed nasal in-situ gel demonstrated suitable physicochemical characteristics, sustained drug release, and enhanced nasal residence, indicating strong potential for nose-to-brain delivery of teriflunomide in multiple sclerosis therapy.

Graphical Abstract

Purpose

Curcuma longa, L., widely termed turmeric is a perennial herb having fleshy rhizomes native to Asia. Rhizomes and dried powder use are traced back to ancient civilizations as an antibacterial, analgesic, digestive aid, anti-inflammatory, and antioxidant. The current article explores the flavonoid extraction from turmeric and its use in the treatment of acne.

Method

Three varieties of turmeric were purchased, identified, dried, powdered, and used to extract flavonoids. The extracted flavonoid-rich fraction was evaluated for flavonoids using preliminary phytochemical tests and thin-layer chromatography. Extract-loaded patches were formulated, optimized for film formation, drug layering, and adhesiveness, and evaluated for quality attributes. The in-vitro drug release, permeation, and antibacterial study were performed using an optimized formulation. Furthermore, a patch was evaluated in the rabbit study for safety.

Results

The authenticated turmeric yields 2–5% flavonoid extract, and its properties comply with the herbal pharmacopeia. The positive response to the alkaline reagent, lead acetate, and the Shinoda test confirmed the presence of flavonoids. The extract showed compatibility with selected polymers, and the formulation was optimized using a combination of ethylcellulose and hydroxypropyl methylcellulose. Evaluation of key parameters—including thickness, weight variation, drug content uniformity, folding endurance, moisture absorption and loss, water vapor transmission rate, and swelling index demonstrates acceptable results. The drug release study demonstrates the controlled release at a Higuchi kinetic model and Korsmeyers-Peppas model mechanism. A significant amount of skin permeation was observed at a controlled rate. The in vitro antimicrobial activity is comparable to standard ciprofloxacin. The skin irritation study in the rabbits demonstrates the safety of the flavonoid formulation for use.

Conclusion

The flavonoid extract from turmeric may be utilized for the treatment of acne using a transdermal patch as an herbal remedy.

Graphical Abstract