Journal of Pharmaceutical Innovation最新文献

{"title":"Eco-Friendly Quality by Design-Based LC–MS/MS Method for the Determination of Nitrosamine Impurities in Triamcinolone Acetonide Pharmaceutical Products","authors":"Lalitha Repudi,&nbsp;Mohana Vamsi Nuli,&nbsp;Pavan Kumar Jaini,&nbsp;Ramanjaneyulu Seemaladinne,&nbsp;Kirankumar Chagarlamudi,&nbsp;Kumaraswamy Gandla","doi":"10.1007/s12247-026-11047-2","DOIUrl":"10.1007/s12247-026-11047-2","url":null,"abstract":"<div><h3>Purpose</h3><p>Nitrosamine impurities are highly potent genotoxic contaminants that present significant safety concerns in pharmaceutical products, necessitating sensitive, robust, and environmentally sustainable analytical methods for their trace-level determination. This study aimed to develop, optimize, and validate an Analytical Quality by Design (AQbD)-based liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the simultaneous quantification of seven nitrosamine impurities—N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodibutylamine (NDBA), N-nitroso-N-methylpropylamine (NMPA), N-nitrosomethyl-4-aminobutyric acid (NMBA), N-nitrosodiisopropylamine (NDIPA), and N-nitrosoethylisopropylamine (NEIPA)—in triamcinolone acetonide (TAA) drug substance and pharmaceutical formulations.</p><h3>Methods</h3><p>The analytical method was systematically developed using the AQbD framework by identifying and optimizing critical analytical parameters to achieve robust chromatographic performance. Chromatographic separation was performed on a Waters ACQUITY™ BEH C18 (50 × 2.1 mm, 1.7 μm) column using gradient elution with acetonitrile and 0.1% (v/v) formic acid in water at a flow rate of 0.8 mL min⁻¹. Detection was carried out in positive electrospray ionization mode using multiple reaction monitoring (MRM). The method was validated according to regulatory guidelines for linearity, accuracy, precision, and sensitivity. Environmental sustainability was evaluated using ComplexGAPI, AGREE, AGREEprep, Analytical Eco-Scale, and White Analytical Chemistry metrics.</p><h3>Results</h3><p>The optimized LC–MS/MS method achieved complete chromatographic separation of all seven nitrosamine impurities within 10 min. The method exhibited excellent linearity over the concentration range of 100–500 ng mL⁻¹ (r² &gt; 0.999), high precision (%RSD &lt; 2%), and satisfactory accuracy with recoveries ranging from 98.2% to 101.4%. Greenness assessment demonstrated excellent environmental sustainability and overall analytical performance. Application of the method to commercially available triamcinolone acetonide drug substance and formulations revealed no detectable levels of the investigated nitrosamine impurities.</p><h3>Conclusion</h3><p>The proposed AQbD-driven LC–MS/MS method is rapid, robust, highly sensitive, and environmentally sustainable for the simultaneous determination of seven nitrosamine impurities in triamcinolone acetonide. Its excellent analytical performance and green credentials make it a suitable platform for routine pharmaceutical quality control, regulatory compliance, and impurity surveillance.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends of Laponite® Clay Mineral as an Excipient in Pharmaceuticals, Cosmetics and Medical Devices: Patent Analysis","authors":"Leticia Farias de Macêdo,&nbsp;Michely Conceição Viana da Costa,&nbsp;Jonas Lira do Nascimento,&nbsp;Viviane Rodrigues de Carvalho,&nbsp;Luiz Henrique Chaves de Macedo,&nbsp;Ana Cristina Figueiredo de Melo Costa,&nbsp;José Lamartine Soares-Sobrinho,&nbsp;Dayanne Tomaz Casimiro da Silva","doi":"10.1007/s12247-026-11017-8","DOIUrl":"10.1007/s12247-026-11017-8","url":null,"abstract":"<div><h3>Purpose</h3><p>This patent-based systematic review investigates the scientific and technological trends involving Laponite®, a synthetic clay mineral composed of disc-shaped nanoparticles. Due to its rheological, structural, and biocompatible properties, Laponite® has gained attention as a versatile excipient in pharmaceutical, cosmetic, and medical device formulations.</p><h3>Methods</h3><p>Patent data were retrieved from The Lens database using the terms “laponite”, “formulation”, “pharmaceutical composition”, “pharmaceutical form”, “drug” and “medicine”. The search covered the period from September 2000 to 2023, yielding 1,134 patent documents. From these, 100 of the most relevant patents were selected for in-depth technical analysis. Data were classified according to jurisdictions, CPC codes, applicants, inventors, and claimed uses.</p><h3>Results</h3><p>The leading jurisdictions were WIPO, the United States and Europe. The most cited CPC codes were C08K3/346, B82Y30/00 and A61L15/60. Top applicants included Procter &amp; Gamble, ExxonMobil Chemical Patents, and LG Chem Ltd. Laponite ® was predominantly applied as a gelling agent, thickener, binder, stabilizer, and drug release carrier. Its multifunctionality supports diverse formulation strategies in the biomedical field.</p><h3>Conclusion</h3><p>Laponite® is a key technological enabler in advanced formulations. Its expanding patent landscape reflects growing scientific and industrial interest in its applications for drug delivery, tissue engineering, and biofunctional materials.</p><p>PROSPERO registration number: CRD420251029805.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-026-11017-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the Efficiency of Nanoliposomes in Cancer Treatment Using Machine Learning Approach","authors":"Mahnaz Ahmadi,&nbsp;Kamyar Davarikia,&nbsp;Samad Azari,&nbsp;Niki Pouyanfar,&nbsp;Niloofar Masoumi,&nbsp;Fatemeh Ghorbani-Bidkorpeh,&nbsp;Bahareh Alizadeh,&nbsp;Seyed Mohammad Ayyoubzadeh","doi":"10.1007/s12247-026-11043-6","DOIUrl":"10.1007/s12247-026-11043-6","url":null,"abstract":"<div><h3>Purpose</h3><p>Nanoliposomes offer tremendous advantages in precise cancer therapy. However, complex design of liposomal formulations, depending on many physicochemical and biological parameters, renders empirical optimization time-consuming. Machine learning (ML) presents an efficient solution to manage such complexity and optimize drug delivery systems.</p><h3>Methods</h3><p>In the current study, an optimal ML workflow was constructed utilizing a dataset containing 786 records from 100 research articles. In this study, five regression algorithms were selected, including Gradient Boosting, Linear Regression, Random Forest, Support Vector Regression (SVR), and XGBoost. The performance of the models was carefully evaluated using 5-fold cross-validation based on Mean Squared Error (MSE), Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), R-squared (R²), and adjusted R-squared (Adj. R²) metrics. Furthermore, SHapley Additive exPlanations (SHAP) was employed for model interpretability.</p><h3>Results</h3><p>Results suggested that ensemble models may capture patterns in the literature-derived dataset; however, given the limited effective sample sizes after preprocessing, these findings should be interpreted as exploratory and potentially optimistic. Gradient Boosting provided an R² of 0.905 (Adj. R² = 0.855), MSE of 50.70, MAE of 5.97, and RMSE of 7.12 for cell viability and Random Forest provided an R² of 0.963 (Adj. R² = 0.883), MSE of 0.0007, MAE of 0.0120, and RMSE of 0.0266 for IC50 (half-maximal inhibitory concentration). SVR demonstrated the best performance (R² of 0.614, Adj. R² = 0.158, MSE of 35778, MAE of 93.4, and RMSE of 189.1) for in vivo tumor growth. Furthermore, Linear Regression exhibited regular low performance consistently. Furthermore, SHAP analysis exhibited major effective features such as concentration, size, zeta potential, and loading efficiency on target variables, offering significant information regarding an optimal nanoliposome design.</p><h3>Conclusion</h3><p>This ML-based approach provides a preliminary and exploratory framework for organizing nanoliposomal formulation data and identifying candidate variables that may influence therapeutic efficacy. Larger datasets and external validation are required before reliable formulation optimization can be claimed. shifting from empirical methods to accelerate the development of highly efficient and customized cancer therapy.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated GC-MS Profiling and Multi-Scale Computational Analyses Identify Promising Phytochemicals Leads Targeting MAPK14 in Colorectal Cancer","authors":"J. Jeeva,&nbsp;K. Girija","doi":"10.1007/s12247-026-11046-3","DOIUrl":"10.1007/s12247-026-11046-3","url":null,"abstract":"<div><h3>Purpose</h3><p>Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide, with MAPK14 (p38 MAPK) playing an important role in tumor progression, immune evasion, cell proliferation, survival, and therapeutic resistance. This study aimed to evaluate the anti-colorectal cancer potential of two GC-MS-identified bioactive molecules against MAPK14 using integrated in silico approaches.</p><h3>Methodology</h3><p>The selected bioactive molecules were subjected to molecular docking against MAPK14 (PDB ID: 1OUY) using the GLIDE module of the Schrödinger suite, with a dihydropyrido-pyrimidine inhibitor as the control molecule. MMGBSA binding free-energy calculations were performed to assess binding affinity. Density functional theory (DFT) calculations, including HOMO–LUMO analysis and molecular electrostatic potential (MESP) mapping, were used to investigate electronic properties. In addition, in silico ADMET profiling and 200 ns molecular dynamics simulations were performed to evaluate pharmacokinetic properties, toxicity, structural stability, and dynamic behaviour. Principal component analysis (PCA) and free energy landscape (FEL) analyses were further employed to characterize conformational dynamics and stability.</p><h3>Results</h3><p>Both bioactive molecules showed favourable binding within the MAPK14 active site, stabilized by hydrogen-bonding and hydrophobic interactions involving key residues, including Lys53, Glu71, Met109, Gly110, and Asp168. MMGBSA analysis supported strong predicted binding affinities, with binding free-energy values below −30 kcal/mol. DFT and MESP analyses demonstrated favourable electronic characteristics and electrostatic complementarity with the binding site. ADMET profiling indicated favourable predicted oral bioavailability and low toxicity. Furthermore, 200 ns molecular dynamics simulations demonstrated stable phytochemical–MAPK14 complexes. PCA and FEL analyses further supported conformational stability, with dominant energy-favourable cluster basins observed in the FEL plots.</p><h3>Conclusion</h3><p>The integrated computational analyses suggest that the selected bioactive molecules possess favourable binding affinity, pharmacokinetic properties, and structural stability against MAPK14. These findings highlight their potential as anti-colorectal cancer leads and provide a basis for further experimental validation.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gallic Acid-Loaded Chitosan Nanoparticles Mitigate Methomyl-Induced Nephrotoxicity in Rats: Associations with Oxidative Stress, Inflammation, and Apoptotic Signaling","authors":"Ahmed MS Hegazy,&nbsp;Ayat B. Al-Ghafari,&nbsp;Huda A. Al Doghaither,&nbsp;Ekramy M. Elmorsy,&nbsp;Ahmad Najem Alshammari,&nbsp;Mohamed Lotfy Abd El-Aziz Ali,&nbsp;Hamada S. Salem,&nbsp;Nagah M. Abourashed","doi":"10.1007/s12247-026-11055-2","DOIUrl":"10.1007/s12247-026-11055-2","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Methomyl (METH) is a widely used carbamate pesticide known to induce renal toxicity associated with oxidative stress, inflammation, and apoptosis. This study investigated the potential nephroprotective effects of gallic acid (GA) and GA-loaded chitosan nanoparticles (GA-CNPs) in male Sprague–Dawley rats. Sixty rats were randomly assigned to six groups: control, GA, GA-CNPs, METH, METH + GA, and METH + GA-CNPs. Free GA and GA-CNPs were compared at a single GA-equivalent dose. Administration of GA-CNPs alone did not significantly alter the measured renal, oxidative, inflammatory, or apoptotic indices compared with the control group (&lt;i&gt;p&lt;/i&gt; &gt; 0.05). METH exposure (1 mg/kg/day for 28 days) significantly impaired renal function, as evidenced by increased serum uric acid, urea, and creatinine levels &lt;b&gt;(&lt;/b&gt;&lt;i&gt;p&lt;/i&gt; &lt; 0.0001 vs. control). Co-administration of GA-CNPs with METH restored these biomarkers toward control levels (&lt;i&gt;p&lt;/i&gt; &lt; 0.05 vs. METH) and produced greater effects than free GA (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). METH exposure also impaired antioxidant defenses, as evidenced by decreased Nrf2 and HO-1 transcript levels, reduced GSH levels, and diminished SOD, CAT, GPx, and GST activities (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001 vs. control). Lipid peroxidation, protein carbonyl content, ROS production, and the oxidative DNA-damage marker 8-OHdG were significantly increased (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001). METH + GA-CNP co-treatment significantly ameliorated these oxidative-stress indices &lt;b&gt;(&lt;/b&gt;&lt;i&gt;p&lt;/i&gt; &lt; 0.05 vs. METH), with greater effects than free GA. Furthermore, METH increased NF-κB, COX-2, TNF-α, IL-1β, and TGF-β transcript levels, consistent with enhanced inflammatory and fibrotic responses, whereas METH + GA-CNP co-treatment significantly attenuated these changes &lt;b&gt;(&lt;/b&gt;&lt;i&gt;p&lt;/i&gt; &lt; 0.05 vs. METH). Bax and caspase-3 transcript levels increased, whereas Bcl-2 transcript levels decreased following METH exposure (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001 vs. control); these alterations were more effectively ameliorated by METH + GA-CNP co-treatment than by free GA (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Histopathological and ultrastructural analyses confirmed severe renal damage in METH-treated rats, which was substantially alleviated in the METH + GA-CNP group, with preservation of glomerular and tubular architecture. In conclusion, at the investigated GA-equivalent dose, co-administration of GA-CNPs with METH provided greater nephroprotection than free GA against METH-induced renal injury. These effects were associated with improvements in oxidative-stress indices and inflammatory, fibrotic, and apoptotic gene-expression profiles. However, these findings do not establish enhanced bioavailability, a dose–response relationship, or definitive pathway-level mechanisms; comparative pharmacokinetic, multidose, and protein-level studies are required.&lt;/p&gt;&lt;h3&gt;Graphical Abstract&lt;/h3&gt;&lt;div&gt;&lt;figure&gt;&lt;div&gt;&lt;div&gt;&lt;picture&gt;&lt;source&gt;&lt;img&gt;&lt;/source&gt;&lt;/picture&gt;&lt;/div&gt;&lt;div&gt;&lt;p&gt;Exposure to methomyl results in sign","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the Solubility of Atovaquone Through the Formation of Carbonated Nanosponges","authors":"Om Sambhaji Shelke,&nbsp;Sumit Kondabarao Sandve,&nbsp;Santosh P. Bahirat","doi":"10.1007/s12247-026-11045-4","DOIUrl":"10.1007/s12247-026-11045-4","url":null,"abstract":"<div><h3>Background</h3><p>The aim of this study is to enhance the solubility and dissolution rate of Atovaquone, a BCS Class II drug, by preparing β-cyclodextrin-based carbonate nano-sponges.</p><h3>Method</h3><p>The carbonate nanosponges were synthesized via a nucleophilic substitution reaction using different molar ratios (1:2:2, 1:4:4, 1:8:8) of β-cyclodextrin, diphenyl carbonate, and N, N-dimethylformamide, and optimized through conventional heating.</p><h3>Results</h3><p>The nanosponges were characterized using FTIR, DSC, particle size analysis, and zeta potential measurements. Solubility studies revealed that the optimal formulation, CNS-4 (molar ratio 1:4:4, reaction time 8 h), exhibited the highest solubilization efficiency, reaching 0.1832 mg/mL—2.34 times that of β-cyclodextrin and 14.19 times that of pure Atovaquone. The drug encapsulation rate was 58.64%, and the saturated solubility of the drug-loaded nanosponges was increased by approximately 10-fold in distilled water and pH 7.4 phosphate buffer (0.1232 mg/mL and 0.1946 mg/mL, respectively). In vitro release studies showed that the cumulative release rate reached 64.78% within 5 h and 99.89% within 8 h in a pH 7.4 buffer, with the release kinetics conforming to a zero-order model (<i>R</i> = 0.9999). Good release characteristics were also observed in simulated gastric fluid and intestinal fluid, both before and after a meal. SEM images revealed that the nanosponge exhibits a spherical, porous structure.</p><h3>Conclusion</h3><p>Phase solubility studies showed that the solubilization efficiency of CNS-4 was 2.34 times that of β-cyclodextrin and 14.19 times that of the pure drug, indicating that the nanosponge’s three-dimensional network provides a higher loading capacity. The study indicates that carbonate nanosponges represent a highly promising delivery system for Atovaquone, capable of significantly enhancing its solubility.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of a Dual-Component Sucralfate-Lidocaine Chewable Softgel for Oral Ulcer Treatment Using Box–Behnken Design","authors":"Neethi M,&nbsp;Samarpan Sarangi,&nbsp;N. Damodharan,&nbsp;P. N. Remya","doi":"10.1007/s12247-026-11049-0","DOIUrl":"10.1007/s12247-026-11049-0","url":null,"abstract":"<div><h3>Background</h3><p>Oral mucosal ulceration is a painful condition that affects mastication, speech, and overall quality of life. Conventional topical formulations often suffer from limited mucosal residence time and poor patient convenience.</p><h3>Objective</h3><p>This study aimed to formulate, optimize, and evaluate a dual-action chewable soft gelatin capsule containing lidocaine and sucralfate for localized oral ulcer management.</p><h3>Methods</h3><p>Chewable softgel capsules were prepared using a rotary die encapsulation technique with a biphasic fill system comprising solubilized lidocaine and suspended sucralfate. Each capsule comprised of 500 mg of sucralfate and 10 mg of lidocaine. A 3 factor, 3 level Box–Behnken design was employed to optimize gelatin concentration, citric acid proportion, and sweetener level. Formulations were evaluated for chewability, disintegration time, lidocaine release at 5 min, and post-chew surface pH.</p><h3>Results</h3><p>Citric acid: fumaric acid proportion significantly influenced disintegration and lidocaine release, while gelatin concentration affected matrix integrity and chewability. The optimized formulation (F14) comprised of 10% w/v gelatin, 70:30 ratio of citric acid and fumaric acid showed acceptable mechanical strength, controlled salivary disintegration within 8–10 min, rapid lidocaine release (~ 92% at 5 min), and acceptable surface pH (6.18–6.60). Taste masking was effective, and short-term stability studies revealed no significant physical or functional changes.</p><h3>Conclusion</h3><p>The optimized chewable softgel demonstrated promising pharmaceutical performance and may potentially serve as an innovative alternative to conventional oral ulcer therapies.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient Nanorod-resourced Lignocellulose from Prosopis juliflora as Synbiotic Delivery System to Mitigate Antibiotic-Induced Gut Edema in Zebrafish Larvae to Combat Gut Dysbiosis","authors":"Preyenga Ramesh,&nbsp;Arockiya Anita Margret","doi":"10.1007/s12247-026-11026-7","DOIUrl":"10.1007/s12247-026-11026-7","url":null,"abstract":"<div><p>Antibiotic-induced dysbiosis of gut microbiota disrupts the homeostasis of intestinal microbes, impairs the integrity of the epithelial barrier, and modulates the gut-brain axis. Here, we developed nanolignocellulose (NLC) from invasive <i>Prosopis juliflora</i> biomass as a sustainable matrix for probiotic delivery and gut protective applications. The NLC was prepared from lignocellulose (LC) by alkali treatment and acid hydrolysis and characterized by dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Probiotic isolates were screened for tolerance to acidic pH, bile salts and osmotic stress and the most resilient isolate isolated from Poongar rice was incorporated in NLC for the development of nanolignocellulose-probiotic beads (NLCPB). Then, prebiotic utilization, biofilm formation, probiotic stability and protective efficacy were tested in an antibiotic induced zebrafish model. The resultant NLC exhibited particle size at nanoscale 104 nm. FTIR and XRD confirmed structural changes associated with nanofibrillation and preservation of characteristic features of cellulose. Following nanofibrillation, a modest increase in relative crystallinity was noted and FTIR analysis showed changes in spectral regions related to lignin and hemicellulose. The selected probiotic was tolerant to the tested stress conditions. Encapsulation in NLC supported probiotic growth, biofilm formation, encapsulation and storage stability. NLCPB FTIR analysis indicated further spectral characteristics related to proteins in accordance with interactions of the probiotic with NLC matrix. NLCPB reduced antibiotic-associated intestinal edema and tissue disruption, and improved intestinal architecture in zebrafish in vivo. Overall, NLC from <i>P. juliflora</i> seems a promising sustainable matrix for probiotic delivery with applications in microbiome-oriented therapeutics, functional foods and gut-brain axis research.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QbD-Driven Development of Angiopep-2 Modified PEGylated Liposomes for Enhanced Brain-Targeted Delivery of Amphotericin B: Formulation Optimization, Pharmacokinetics and Brain Distribution","authors":"Yu Zhang,&nbsp;Shengnan Lu,&nbsp;Ling Cheng,&nbsp;Mengfang Chen,&nbsp;Jing Li,&nbsp;Feng Su,&nbsp;Guangwei He","doi":"10.1007/s12247-026-11056-1","DOIUrl":"10.1007/s12247-026-11056-1","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;p&gt;Amphotericin B (AmB) is the first-line agent for &lt;i&gt;cryptococcal meningitis&lt;/i&gt; (CM). However, its therapeutic efficacy is severely limited by poor blood-brain barrier (BBB) permeability, resulting in inadequate brain distribution even with commercial liposomal formulations. The development of an active brain-targeted delivery system capable of receptor-mediated transcytosis (RMT) represents a promising strategy to overcome this limitation.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Quality by Design (QbD) principles were employed to optimize AmB-loaded liposomes (AmB/Lip) using DSPC as the primary membrane material via thin-film hydration. Single-factor experiments and Box-Behnken design-response surface methodology (BBD-RSM) were systematically applied to optimize formulation and process parameters. Long-circulating liposomes (AmB/PEG-Lip) and Angiopep-2-modified brain-targeted liposomes (AmB/PEG-Ang-Lip) were subsequently constructed by incorporating DSPE-mPEG&lt;sub&gt;2000&lt;/sub&gt; and DSPE-PEG&lt;sub&gt;2000&lt;/sub&gt;-Angiopep-2, respectively. Comprehensive quality evaluations were performed, including particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE%), morphology, storage stability, serum stability, and in vitro release profiles. Plasma pharmacokinetics of the three formulations and brain distribution of AmB/PEG-Ang-Lip were investigated following intravenous administration (1.0 mg/kg) in Sprague-Dawley (SD) rats using a validated HPLC-MS/MS method.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The optimized AmB/Lip formulation exhibited the PS of 125.0 ± 0.90 nm, PDI &lt; 0.3, zeta potential &gt; 30 mV (absolute value), EE% of 92.13 ± 0.54%, and drug loading of 5.29 ± 0.06%. The optimal PEGylation and Angiopep-2 modification molar ratios were determined as 5% and 0.5%, respectively. AmB/PEG-Lip and AmB/PEG-Ang-Lip showed particle sizes of 107.2 ± 1.13 nm and 113.5 ± 1.85 nm, respectively, with EE% exceeding 90% for both. All three formulations demonstrated good stability at 4 °C over 28 days and maintained colloidal stability in 10% fetal bovine serum. PEGylation significantly sustained drug release, with 72 h cumulative release rates of 17.51% (AmB/Lip), 9.81% (AmB/PEG-Lip), and 12.11% (AmB/PEG-Ang-Lip). Pharmacokinetic analysis revealed that AmB/PEG-Ang-Lip exhibited significantly prolonged elimination half-life (T&lt;sub&gt;1/2&lt;/sub&gt;: 16.23 ± 7.15 h) and reduced clearance (CL: 0.69 ± 0.30 mL/kg/min) compared to AmB/Lip. Brain distribution studies revealed rapid brain accumulation with T&lt;sub&gt;max&lt;/sub&gt; of 0.25 h and C&lt;sub&gt;max&lt;/sub&gt; of 118.00 ng/mL (approximately 472.0 ng/g tissue) in whole-brain homogenates, appeared to achieve higher brain accumulation than clinically reported AmB formulations at a lower dose in cross-study comparisons. However, these findings require confirmation through head-to-head studies.&lt;/p&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;This study successfully constructed Angiopep-2-modified brain-targeted AmB liposomes with favorable ","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Novel Pyrazolopyranopyrimidine Acyclic Nucleosides Disubstituted at N2/C5 as Potential Anti-SARS-CoV-2 Inhibitors: Structural Characterization, and In Silico Studies","authors":"Ezaddine Irrou,&nbsp;Younesse Ait Elmachkouri,&nbsp;Rakibul Islam,&nbsp;Devendra Kumar Dhaked,&nbsp;Yassine Riadi,&nbsp;Pranjal Kishor Mahindrakar,&nbsp;Mohammed H. Geesi,&nbsp;Ali Altharawi,&nbsp;Manal A. Alossaimi,&nbsp;Mohamed Labd Taha","doi":"10.1007/s12247-026-11040-9","DOIUrl":"10.1007/s12247-026-11040-9","url":null,"abstract":"<div><h3>Background</h3><p>Lower respiratory tract infections are a major global cause of death, with around 2.5 million deaths recorded in 2021. A substantial proportion of these infections are viral in origin, primarily caused by pathogens such as influenza virus, respiratory syncytial virus (RSV), and SARS-CoV-2.</p><h3>Objective</h3><p>The present study aimed to design and synthesize novel pyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine acyclonucleosides bearing HBG-derived pseudosugar moieties as potential antiviral agents targeting key SARS-CoV-2 proteins.</p><h3>Methods</h3><p>A series of novel derivatives 2–8 was synthesized in satisfactory yields through a multi-step synthetic strategy involving the construction of a fused pyrazolo-pyrano-pyrimidine scaffold incorporating a pyran ring as a spacer between the pyrazole and pyrimidine fragments. All synthesized compounds were structurally characterized using advanced spectroscopic techniques, including ¹H, ¹³C, and DEPT-135 NMR spectroscopy, and high-resolution mass spectrometry (HRMS). The compounds were computationally evaluated against MPro, PLPro, and RdRp using molecular docking, molecular dynamics simulations, MM-GBSA binding free energy calculations, and AD-MET analysis.</p><h3>Results</h3><p>The computational results revealed stable ligand–protein interactions and favourable binding profiles compared with the co-crystallized ligands (CCLs). In MPro, ligands 3S and 7S formed key interactions with several active-site residues (N142, M49, M165, G143, and E166), among which N142, M49, and G143 were common to both ligands. Notably, N142 contributed most significantly to ligand binding. In PLPro, both ligands (2S and 8R) formed stable π–π interactions with Y268, enhancing complex stability and contributing more than 7 kcal/mol to the binding free energy. Other major contributing residues included Y264, P247, and P248. In RdRp, residues Y38, F45, and Y728 were critical for ligand stabilization, contributing more than 8 kcal/mol to the binding free energy. MM-GBSA energies confirmed strong binding of 3S and 7S to MPro, outperforming the CCL, while 2S and 1R exhibited binding affinities comparable to those of the CCLs in PLPro and RdRp, respectively.</p><h3>Conclusion</h3><p>The ADMET profiles were favourable, suggesting that these ligands are promising candidates for further experimental validation as potential SARS-CoV-2 antiviral agents.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}