Journal of Pharmaceutical Innovation最新文献

Background

The search for antiviral therapeutics during the COVID-19 pandemic has reignited interest in natural products, particularly those derived from soil microorganisms. Historically, soil has yielded antibiotics and some antiviral agents, but the deeper ecological logic behind these discoveries has remained underexplored. We propose a refined perspective—the Soil Hypothesis—which does not simply state that nature harbors solutions to viral threats, but that the intricate molecular ecology of soil ecosystems is evolutionarily structured to generate consortia of bioactive metabolites with antiviral potential.

Objective

To reinterpret the antiviral capacity of soil-derived compounds, exemplified by ivermectin, through the lens of ecological systems biology, and to advance the Soil Hypothesis as a framework linking microbial interaction networks to the emergence of antiviral metabolite ensembles.

Methods

A structured literature synthesis was performed across major scientific databases (PubMed, Scopus, EMBASE, and ClinicalTrials.gov), focusing on ivermectin, rapamycin, cyclosporine, and teicoplanin—each a soil-derived compound. Data were analyzed to identify recurring pharmacological and ecological patterns relevant to antiviral activity and immune modulation.

Results

Findings indicate that these soil-derived agents exert antiviral and immunomodulatory effects through diverse molecular pathways—ranging from inhibition of viral entry and replication to modulation of host inflammatory signaling. These functions emerge not from isolated molecules but from a metabolite network evolved within competitive soil ecologies. The convergence of multiple soil-origin compounds with antiviral relevance supports the hypothesis that soil ecosystems act as molecular incubators where chemical diversity and microbial co-evolution continually generate antiviral solutions.

Conclusion

The Soil Hypothesis extends beyond the traditional notion that “nature provides remedies.” It posits that the soil biome constitutes a dynamic, evolutionarily optimized pharmacological environment, where microbial consortia collectively produce structurally diverse and functionally synergistic metabolites with antiviral properties. Recognizing soil as a complex, self-optimizing biochemical system reframes it as an ecological template for future antiviral discovery efforts.

Purpose

Fungal infections remain a major concern due to rising incidence related to immunosuppression and chemotherapy, alongside growing antifungal resistance. Though Voriconazole (VCZ) displays robust potential against infections like aspergillosis and candidemia, its limited formulation availability highlights the need for alternative delivery approaches. Nanovesicle-based systems like novasomes (NV) have emerged as promising systems capable of enhancing delivery and overcoming current therapeutic limitations.

Methods

2³ factorial design was adopted to develop VCZ-loaded NV, with optimization based on entrapment efficiency (EE), vesicle size (VS), polydispersity index (PDI), and zeta potential (ZP), alongside evaluation of in-vitro release behavior, antifungal activity, Fourier transform infrared spectroscopy (FTIR), morphological characteristics, and stability of the optimized formula. The optimized formulation was incorporated into a Carbopol gel (DN1G) for ex vivo permeation studies.

 Results

The formulation was optimized through a 2³ factorial design with EE%, VS, PDI, and ZP as critical responses, yielding the optimized VCZ-loaded NVs (DN1) with EE% (97.27±0.12 %), VS (256.93±4.40 nm), PDI (0.27±0.00), and ZP (-47.63±0.92 mV).In-vitro release studies confirmed controlled and sustained release. FTIR showed compatibility with the excipient, TEM analysis revealed spherical, non-aggregated vesicles, and stability evaluation revealed no significant alterations in selected parameters. DN1 demonstrated potent antifungal activity (MIC of 0.25 µg/mL) against C. albicans, and its incorporation into gel (DN1G) enhanced VCZ permeation by 1.89-fold.

Conclusion

This study highlights the potential of NV as a promising approach for VCZ, offering an effective alternative to conventional VCZ formulations, and encourages further exploration of vesicular systems for antifungal therapy.

Graphical Abstract

This study aimed to develop a linezolid-loaded film-forming solution for treating diabetic foot ulcers, enhancing patient compliance and therapeutic efficacy. Linezolid was selected due to its antimicrobial properties, which aid in wound healing. To prevent drug interactions, topical film-forming solutions are derived from biodegradable polymers, such as chitosan. To prepare the 2% chitosan solution in 1% acetic acid for the FFS. The medication distribution was homogeneous, including linezolid, dissolved in ethanol and polyethene glycol 400 (PEG 400) as a plasticiser. The goal of this strategy was to provide a consistent supply of medication for effective infection control. Using design expert software, nine formulations (F1-F9) were developed, with F6 being optimised for its reduced drying time, low viscosity, and superior drug release. Zero-order linear drug release with sustained-release characteristics was shown in in vitro experiments. Comparing the optimised formulation group to a commercial product, animal tests demonstrated superior wound healing; a histo-morphological study showed less inflammation and increased epithelium regeneration. In conclusion, the optimised linezolid-loaded FFS presents a potentially effective therapeutic option for diabetic foot ulcers, improved healing, and continuous drug release. When used topically, it decreases medication interactions and increases patient compliance.

Graphical Abstract

Purpose

The rapid advancement of Internet of Things (IoT) technologies has significantly augmented data generation, particularly in the geographic sphere. This investigation confronts the pivotal issue of effective data management in IoT-integrated healthcare applications, with a specific emphasis on Telangana’s ‘Medicine from the Sky’ initiative, which employs Beyond Visual Line of Sight (BVLoS) flights to facilitate the delivery of medical supplies to isolated regions.

Methods

Acknowledging the constraints of prevailing data retrieval methodologies, this study introduces an innovative hybrid indexing approach that combines the advantages of bitmap indexing and R-tree indexing to enhance the data retrieval efficacy.

Results

The proposed methodology employs PostgreSQL in conjunction with the PostGIS extension and Python for performance assessment, illustrating the efficacy of the hybrid indexing technique.

Conclusions

The outcomes of this research contribute to the formulation of effective data management frameworks within IoT applications, especially in the healthcare sector, thereby improving the accessibility and prompt delivery of vital medical supplies to marginalized communities.

Background

Unmet medical needs persist across various therapeutic areas, underscoring the necessity for expanded treatment options. The United States Food and Drug Administration (USFDA) addresses these needs by approving efficacy supplements to New Drug Applications NDAs, allowing for the inclusion of new indications, dosing regimens, or patient populations for existing drugs. This mechanism supports the efficient utilization of prior clinical data to expedite access to vital therapies.

Objective

This study aims to examine trends in the USFDA’s NDA efficacy supplement approvals from 2019 to 2023, emphasizing their role in bridging therapeutic gaps.

Methods

Approval data was sourced from the USFDA database. The analysis focused on annual approval trends, dosage forms, key companies, and therapeutic areas.

Results

A total of 246 efficacy supplements were approved between 2019 and 2023. Oncology led with 38.4% of approvals, followed by cardiovascular (10.8%) and neurology (9%). Tablets (45.8%) and injections (25%) were the most common dosage forms. Leading companies included AstraZeneca, AbbVie, and Merck.

Conclusion

Efficacy supplements, submitted as NDA supplements, play an important role in expanding therapeutic options. While not all such approvals directly address unmet medical needs, they often contribute to incremental innovation and patient-centric regulatory pathways. The analysis highlights that approvals have remained relatively steady in recent years, underscoring the FDA’s ongoing role in facilitating adaptive regulatory mechanisms and supporting the availability of broader treatment choices.

Objective

This research intended to establish a curcumin nanosuspension micro-pellets (CUR-NSP) delivery system combining Hummer acoustic resonance (HAR) and fluidized bed coating technologies.

Methods

Polyvinylpyrrolidone K30 and sodium lauryl sulfate were employed as stabilizers to optimize and scale up the preparation of curcumin nanosuspension (CUR-NS) via HAR equipment. Using CUR-NS as the coating medium, the fluidized bed coating process for CUR-NSP was optimized through experimental design methodologies.

Results

First, this study prepared CUR-NS, which reduced the average particle size of raw curcumin from 5.38 ± 2.46 μm to 95.9 ± 0.46 nm. Under the optimal coating conditions, the redispersed CUR-NSP exhibited an average particle size of 104.86 ± 0.34 nm, a polydispersity index of 0.180 ± 0.002, a Zeta potential of -36.24 ± 0.80 mV, and a pellets yield of 97.14 ± 0.12%. Furthermore, this study evaluated the solidification efficiencies of fluidized bed coating, freeze drying, and rotary evaporation for CUR-NS. Structural characterizations via DSC, XRD, and FTIR confirmed the interaction between curcumin and stabilizers, along with partial amorphization. Saturation solubility tests demonstrated that CUR-NSP increases the solubility of curcumin in hydrochloric acid buffer solution at pH 1.2 and phosphate buffer solution at pH 6.8 by 2221.4 and 2761.89 times, respectively. In vitro dissolution tests indicated that CUR-NSP releases rapidly within 5 min.

Conclusions

The combination of HAR and fluidized bed coating enables an efficient and feasible approach for preparing CUR-NSP, addressing the issue of poor solubility.

Purpose

The study aimed to enhance the physicochemical and pharmacological properties of albendazole by developing cocrystals with para-hydroxybenzoic acid (PHBA) as a coformer, thereby improving its solubility, dissolution rate, and therapeutic efficacy while minimizing hepatotoxicity.

Methods

Albendazole–PHBA cocrystals were synthesized using the lyophilization technique. Solid-state characterization was performed through differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM) to confirm cocrystal formation. Molecular interactions were elucidated using Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (¹H NMR) spectroscopy. Saturation solubility and in-vitro dissolution studies were conducted in different media (0.1N HCl, phosphate buffer pH 6.8, and distilled water pH 7.0). Molecular docking studies were performed to predict the binding affinity of albendazole and its cocrystals with α- and β-tubulin targets.

Results

DSC, PXRD, and SEM analyses confirmed successful formation of albendazole–PHBA cocrystals. Spectroscopic studies indicated hydrogen bonding between the C=O group of PHBA and the N–H group of albendazole. Solubility increased by 1.24-fold in 0.1N HCl, 91.94-fold in phosphate buffer (pH 6.8), and 119.49-fold in distilled water compared to the pure drug. The cocrystals exhibited significantly improved dissolution rates in both acidic and neutral media. Reduced hepatotoxicity were observed relative to pure albendazole. Molecular docking revealed stronger binding affinity and lower binding energy for cocrystals with tubulin targets.

Conclusion

Albendazole–PHBA cocrystals demonstrated marked improvements in solubility, dissolution behavior, and therapeutic performance, along with reduced hepatotoxicity. This study underscores the potential of cocrystallization with phenolic acid coformers as an effective approach for optimizing the bioavailability and safety of poorly soluble antiparasitic drugs.

Purpose

The transfer of pharmaceutical agents into breast milk poses a critical safety concern for breastfeeding infants, necessitating precise prediction of milk-to-plasma (M/P) concentration ratios for safe and effective pharmacotherapy during lactation. This study aims to develop an innovative Quantitative Structure-Property Relationship (QSPR) model to predict the logarithm of the M/P ratio (log(M/P)) using a curated dataset of 100 structurally diverse pharmaceuticals. The study explores whether QSPR can enhance early risk assessment, optimize lead compounds, and reduce reliance on resource-intensive experimental trials.

Methods

The QSPR model was constructed using Monte Carlo optimization, employing conformation-independent SMILES-based descriptors (both local and global) and graph-theoretical invariants, such as extended connectivity indices and path counts. The dataset was randomly divided into 75:25 training-test subsets across three independent runs, with validation conducted via internal cross-validation, external testing, y-randomization, and applicability domain analysis using the statistical defect approach.

Results

The models exhibited strong predictive performance, with training set coefficients of determination (R²) ranging from 0.8716 to 0.8808 and test set R² peaking at 0.9232. Additional metrics, including Concordance Correlation Coefficient (CCC up to 0.9366), Index of Ideality of Correlation (IIC up to 0.9608), and mean absolute error (MAE as low as 0.1657), confirmed accuracy and generalizability. SMILES-based analysis identified molecular fragments with positive and negative impact on log(M/P.

Conclusion

This study establishes conformation-independent QSPR modeling as an important tool for early-stage drug development and pharmacovigilance, providing actionable insights to minimize infant exposure and improve maternal and infant health outcomes for breastfeeding women through safer therapeutic options. 

Graphical Abstract

Ischemic stroke (IS) accounts for approximately 70% of global stroke cases and remains a leading cause of mortality and disability due to the limitations of conventional drug delivery systems in overcoming the blood-brain barrier (BBB). This study presents an innovative nanotechnology-based intranasal drug delivery system utilizing aminated chitosan (AmCs) nanoparticles encapsulating thymoquinone (TQ), a bioactive neuroprotective compound. The optimized TQ-AmCs nanoparticle formulation exhibited a particle size of 135.9 nm, an entrapment efficiency of 87.75%, and a sustained drug release of 88.46% over 24 h. Pharmacokinetic studies demonstrated a 75.21% drug targeting efficiency index (DTI) and a 2.5-fold increase in bioavailability compared to conventional formulations. Ex vivo studies confirmed a 1.5-fold enhancement in nasal mucosa permeability, ensuring efficient nose-to-brain delivery. Brain pharmacokinetic analysis further revealed significantly higher Cmax (41.61 µg/mL), AUC (49.87 µg h/mL), and mean residence time (MRT) (26.87 h) for intranasally administered TQ-AmCs nanoparticles compared to traditional formulations. These findings, supported by extensive in vitro, ex vivo, and in vivo studies, underscore the potential of nanotechnology-enhanced intranasal drug delivery as a transformative approach for ischemic stroke therapy, offering superior brain-targeting efficiency and prolonged neuroprotection.

Graphical Abstract

Cyclin-dependent kinase 2 (CDK2) is an essential regulator of cell cycle progression and a potential target for cancer treatment. Although Andrographolides, the bioactive diterpenoid lactones obtained from Andrographis paniculata, have shown a variety of pharmacological effects, their mechanistic potential as CDK2 inhibitors is rarely explored. This work utilised a thorough in silico methodology to assess specific andrographolides as inhibitors of CDK2. Structural and electronic investigations, encompassing HOMO-LUMO calculations, NBO analysis, and RDG studies, demonstrated advantageous electronic characteristics and possible reactive sites that facilitate robust interactions with CDK2. ADMET calculations indicated satisfactory pharmacokinetic profiles and drug-likeness of the chosen compounds. Molecular docking investigations revealed strong binding affinities, subsequently confirmed by molecular dynamics (MD) simulations that exhibited stable protein-ligand conformations. Calculations of binding free energy utilising MM-GBSA validated robust and persistent interactions, with specific derivatives demonstrating notably advantageous energetics. Our comprehensive computational analysis identifies andrographolides as possible CDK2 inhibitors, offering significant insights for forthcoming experimental validation and prospective development as anticancer agents.

Graphical Abstract