Journal of Pharmaceutical Innovation最新文献

{"title":"Plant-Derived Hydrolates as Functional Components in Topical Gel and Emulgel Platforms: A Comparative Evaluation of Hydrolate-Based Semisolid Systems","authors":"Laís S. Luz,&nbsp;Lucas Ythallo da Silva Delamarque,&nbsp;Amanda Mara Teles,&nbsp;Carla Janaina Rebouças Marques do Rosário,&nbsp;Walter Luis Teixeira Neves Junior,&nbsp;Antonio Manoel da Cruz Rodrigues,&nbsp;Luiza Helena Meller da Silva,&nbsp;Renato Sonchini Gonçalves","doi":"10.1007/s12247-026-11145-1","DOIUrl":"10.1007/s12247-026-11145-1","url":null,"abstract":"<div><h3>Purpose</h3><p>Plant-derived hydrolates are aqueous co-products of hydrodistillation that remain underexplored despite their potential as sustainable ingredients for topical formulation design. This study comparatively evaluated two topical semisolid platforms for hydrolate valorization: a thermoresponsive gel containing <i>Anacardium occidentale</i> L. hydrolate and an emulgel containing <i>Pectis brevipedunculata</i> hydrolate associated with babassu oil.</p><h3>Methods</h3><p>Both systems were based on Pluronic F127 and Carbopol 974P and were characterized by physical stability assessment, Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and semiquantitative antimicrobial screening against <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Candida albicans</i>.</p><h3>Results</h3><p>Incorporation of the whole hydrolate-containing aqueous fractions into the complete formulations was associated with formulation-dependent changes in matrix organization and resazurin-based metabolic activity scores. The <i>A. occidentale</i> hydrolate-loaded gel showed a visually observed temperature-associated change in physical form, spectroscopic evidence compatible with non-covalent hydrolate–polymer interactions, reduced crystallinity, compact lamellar morphology, and a lower resazurin score at the highest tested formulation condition.​ The <i>P. brevipedunculata</i> hydrolate-loaded emulgel preserved the structural identity of the polymer–lipid matrix and showed a descriptive one-point lower score against <i>C. albicans</i> at the lower tested formulation condition.</p><h3>Conclusion</h3><p>Because hydrolate chemical profiles, droplet-size analysis, zeta potential, rheology, pH, release/permeation, and cytocompatibility assays were not performed, the findings should be interpreted as preliminary formulation-level evidence rather than direct mechanistic, safety, or efficacy proof. Overall, this study supports further investigation of plant-derived hydrolates as value-added aqueous co-products in sustainable topical semisolid platforms.</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":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-026-11145-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338709","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":"Development and Validation of the First LC-MS/MS Assay for Tenalisib in Mice Plasma: Application to a Pharmacokinetic Study","authors":"Biradar Yogesh Balaji,&nbsp;Sireesha Dodda","doi":"10.1007/s12247-026-11146-0","DOIUrl":"10.1007/s12247-026-11146-0","url":null,"abstract":"<div><h3>Objective</h3><p>To develop and validate an LC-MS/MS method for the quantification of Tenalisib, a dual phosphoinositide 3-kinase δ/γ inhibitor in mouse plasma.</p><h3>Methods</h3><p>Protein precipitation technique was employed to extract Tenalisib from mouse plasma, with tolbutamide selected as the internal standard (IS). A clean chromatographic separation of Tenalisib and the IS was achieved on a Zorbax SB Phenyl (50 × 4.6 mm, 3.5 μm) column using an isocratic mobile phase (0.1% formic acid in 5mM ammonium formate and acetonitrile; 40:60%, v/v) delivered at a flow rate of 0.9 mL/min.</p><h3>Results</h3><p>The MS/MS transitions monitored were <i>m/z</i> 416.2→252.2 and 271.1→154.9 for Tenalisib and Tolbutamide, respectively. Method validation was performed in accordance with USFDA guidelines and all the results met the acceptance criteria. The method was demonstrated to be accurate and precise at a linearity range of 2-4000 ng/mL. The intra and inter-day precision for Tenalisib in mouse plasma ranged from 4.03 to 7.84 and 6.07–10.5%, respectively. Tenalisib was stable under a series of stability conditions.</p><h3>Conclusion</h3><p>The developed LC–MS/MS method demonstrates suitability for pharmacokinetic studies in BALB/c mice following intravenous and oral route of administration and the results were confirmed by incurred sample reanalysis.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338756","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":"Correction to: Comparative Development of Separate Sodium Caseinate Nanoparticle Formulations of 5-Fluorouracil and 5-Fluorouracil-1-acetic Acid: Physicochemical, In Vitro, and Ex Vivo Evaluation","authors":"Nisha Agari Bhatt,&nbsp;Ashok Behera,&nbsp;Aman Chaudhary,&nbsp;Jhuma Samanta","doi":"10.1007/s12247-026-11142-4","DOIUrl":"10.1007/s12247-026-11142-4","url":null,"abstract":"","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338182","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":"Flow Excursion and Mixing in the Kneading Block Section of Hot-Melt Extrusion Induced by Carrier Density Variation","authors":"Qi Shen,&nbsp;Wutong Wu,&nbsp;Huagui Li,&nbsp;Yibiao Chen,&nbsp;Hongming Zhou","doi":"10.1007/s12247-026-11143-3","DOIUrl":"10.1007/s12247-026-11143-3","url":null,"abstract":"<div><p>Thermal melt extrusion is commonly used to improve the dissolution and bioavailability of poorly soluble active pharmaceutical ingredients. However, the selection of carriers is mostly based on experience, and the influence of carrier density on the mixing in the kneading block zone is still unclear. In this study, a three-dimensional transient finite element flow model of the kneading block zone was established, and the shear-thinning viscosity was updated in real time, coupled one-way convection–diffusion tracking and tracer particles were used to compare the flow and mixing under five carrier density conditions. The results showed that compression causes interface deformation, the high-viscosity active pharmaceutical ingredients protrude from the center to the carrier side, and the carrier penetrates into its enrichment zone from the top and bottom; at the same time, the density effect is the strongest when compressing the two phases, and the low carrier density enhances the offset, while the single-phase compression has a smaller influence. The shear rate is the highest at the junction of the tip and side of the kneading block, which is positively correlated with the flow rate and negatively correlated with the viscosity. Alternating compression and detachment lead to local acceleration and reflux, and the residence time shows a bimodal distribution, with a shorter residence time for high carrier density; the dispersion index first increases rapidly and then fluctuates and decreases. After thorough mixing, the final uniformity depends more on the density difference between the carrier and the active pharmaceutical ingredient, and the smaller the density difference, the more uniform it is. Conclusion: Carrier density affects the mixing efficiency through the shear-thinning response, the interface offset, and the shear thinning response. Carrier screening and process design should consider density matching as an important parameter, rather than relying solely on trial and error.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338479","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":"An Integrated Bioinformatics and Biophysical Approach for Identification of Novel Inhibitors Targeting the KRAS G12C-PI3Kα Signaling Pathway","authors":"Bayan T. Bokhari","doi":"10.1007/s12247-026-11139-z","DOIUrl":"10.1007/s12247-026-11139-z","url":null,"abstract":"<div><p>KRAS mutations, mainly G12C, hyperactivate oncogenic signaling in breast cancer, promoting tumor proliferation, metastasis, and resistance to standard treatments through dysregulated downstream effectors like PI3K/AKT/mTOR. Direct targeting of KRAS remains difficult due to its undruggable GTPase pocket, highlighting the need for innovative computer-aided drug design (CADD) and biophysics strategies. In this study, various approaches were employed to identify potential KRAS inhibitors. Molecular docking analysis with PyRx 0.8 predicted binding free energies of -10.3 kcal/mol, -10.3 kcal/mol, and − 10.1 kcal/mol for Top-1, Top-2, and Top-3, respectively. The top-ranked docked compounds were further examined through molecular dynamics simulations to assess the stability of the complexes. A 100-ns simulation confirmed their stability, showing minimal deviations throughout the entire period. Additionally, favorable MM-PBSA net binding energies validated these lead compounds for targeting PI3Kα-mutant breast cancer. SwissADME analysis and physicochemical properties, including Lipinski’s rule of five, confirmed that these compounds possess drug-like characteristics. RMSD analysis revealed an initial increase during the equilibration phase, followed by stable convergence during the simulation. Notably, the Top-1 ligand-protein complex exhibited the lowest RMSD values, around 4.29 Å with minor fluctuations, indicating a highly stable binding conformation. Furthermore, RMSF analysis demonstrated that the Top-1 ligand remained the most biologically relevant and dynamically stable over the 100-ns simulation, suggesting its potential for sustained inhibitory activity in breast cancer treatment. Next, the compactness and relaxation of the ligand-protein complexes were investigated via radius of gyration (Rg) and B-factor analysis. All the selected top-three ligand-protein docked complexes showed comparatively stable Rg values during simulation time, signifying the constant structural integrity of the complexes. Furthermore, the overall Rg plots of each docked complex analysis specify that ligand binding does not significantly destabilize the overall protein structure. MM-GBSA binding free energy calculation predicted − 107.3 kcal/mol, -104.32 kcal/mol, and − 96.67 kcal/mol net free binding energy for Top-1. Top-2 and Top-3, respectively. MM-PBSA analysis predicted − 105.85 kcal/mol, -102.22 kcal/mol, and − 95.04 kcal/mol net binding for Top-1. Top-2 and Top-3, respectively. Overall, bioinformatics, biophysics screening, and binding free energy calculation findings showed that the selected Top-1 ligand is the most biologically relevant and stable in the dynamic, highlighting its potential as a drug candidate for the treatment of breast cancer.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149339323","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":"Green-synthesized CuO–ZnO Nanoparticles: Anticancer Efficacy, Antioxidant Activity and Biocompatibility Compared to Monometallic Counterparts","authors":"Iram Saba,&nbsp;Khair-Un- Nisa,&nbsp;Muhammad Zubair,&nbsp;Muhammad Nadeem Zafar,&nbsp;Umer Younas,&nbsp;Uswa Amin,&nbsp;Abu Bakar Siddique,&nbsp;Zartasha Safdar,&nbsp;Norah Alwadai,&nbsp;Fakhr-E- Alam,&nbsp;Samia Nadeem,&nbsp;Munawar Iqbal","doi":"10.1007/s12247-026-11135-3","DOIUrl":"10.1007/s12247-026-11135-3","url":null,"abstract":"<div><h3>Objectives</h3><p>The present investigation was carried out to synthesize monometallic copper (CuONPs), zinc (ZnONPs) and bimetallic copper oxide-zinc oxide nanoparticles (CuO-ZnO NPs) via a green route using <i>Allium cepa</i> (onion) and <i>Zingiber officinale</i> (ginger) extracts.</p><h3>Methods</h3><p>The prepared NPs were analyzed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy and ultraviolet–visible (UV–Vis) spectroscopy. Following characterization, the NPs were assessed for their antimicrobial, antioxidant and anticancer activities. The anticancer activity was evaluated against the MCF-7 breast cancer and HepG2 hepatic cell lines. Hemolytic activity was evaluated to assess cytotoxicity.</p><h3>Results</h3><p>The bimetallic CuO–ZnO NPs exhibited superior biological performance compared to their monometallic counterparts. The CuO–ZnO NPs demonstrated enhanced anticancer activity relative to CuONPs and ZnONPs. In vitro cytotoxicity against hepatocellular carcinoma (HepG2) cells assessed by the MTT assay showed a dose-dependent reduction in cell viability. Notably, CuO–ZnO NPs showed the higher inhibition (52.64%, 100 µg/mL) followed by CuONPs (33.02%, 100 µg/mL) and ZnONPs (34.60% at 100 µg/mL). In addition, all synthesized NPs exhibited promising antioxidant activity, as determined by the DPPH radical scavenging assay, with CuONPs, ZnONPs and CuO-ZnO NPs achieving scavenging efficiencies of 65%, 70% and 86% at 1500 µg/mL, respectively. Also, the NPs showed promising activity against <i>S. aureus</i> and <i>B. subtilis</i> (microbes) and <i>A. niger</i> and <i>R. solani</i> (fungal) strains.</p><h3>Conclusion</h3><p>The green-synthesized CuO–ZnO bimetallic NPs demonstrated promising anticancer, antioxidant and antimicrobial performance compared to monometallic counterparts, along with acceptable biocompatibility. These findings highlight their potential as promising multifunctional nanomaterials for biomedical and pharmaceutical applications.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149339519","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":"Enteric-Coated Metformin Tablets: In vitro Release and Metabolic Outcomes in High Fat Diet Fed Rats","authors":"Bushra Mohammed Yaseen,&nbsp;Musab Mohammed Khalaf,&nbsp;Myasar Alkotaji","doi":"10.1007/s12247-026-11132-6","DOIUrl":"10.1007/s12247-026-11132-6","url":null,"abstract":"<div><h3>Background</h3><p>Metformin hydrochloride is a first line oral antidiabetic medication, and it is known to cause weight loss as a side effect. The exact mechanism responsible for this side effect is unknown. In addition, the administration of a conventional immediate-release tablet of metformin is associated with gastrointestinal side effects. Enteric coating can modify metformin release in vitro, and this pH-dependent dissolution could establish an intestinal localization, which may aid in the GLP-1-mediated mechanism in vivo.</p><h3>Objective</h3><p>To evaluate enteric-coated metformin tablets and compare post-treatment metabolic outcomes with immediate-release metformin, liraglutide, and dietary controls in male Sprague-Dawley rats.</p><h3>Methods</h3><p>Seven nominal 70-mg cores containing 40 mg metformin hydrochloride were formulated and screened. F7 was selected and coated with Kollicoat MAE 30 DP (FEC1) or Eudragit L100 (FEC2). Sixty rats were assigned to five groups (12/group). After five months of high-fat feeding, treatment continued for eight weeks; the normal-diet control remained on standard feed. Metformin was administered at 40 mg/rat/day; FEC2 was used in vivo. Only post-treatment outcomes were measured.</p><h3>Results</h3><p>FEC1 and FEC2 released 8 ± 2% and 6 ± 1.5% in acid after two hours, and 82 ± 3% and 78 ± 3% in pH 6.8 buffer at 45 min. Final body weight did not differ significantly among groups (F(4,55) = 1.175; <i>p</i> = 0.332). No enteric-coated versus immediate-release contrast was significant across nine outcomes after Holm correction. Enteric-coated metformin had higher measured GLP-1 immunoreactivity and lower total and LDL cholesterol than untreated HFD in exploratory adjusted.</p><h3>Conclusion</h3><p>The formulations showed acid resistance and pH-dependent release in vitro. Enteric-coated metformin formulation showed a more favorable profile than immediate-release metformin formulation, particularly through higher GLP-1 response, stronger LDL reduction, while maintaining comparable glucose lowering effect. The superior reduction (although not significant) in body weight and other anthropometric parameters observed with enteric-coated metformin indicates that altering metformin release characteristics through formulation design may improve its weight management efficacy.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149339179","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":"Co-Assembly of Ribavirin and TMC353121 Nanoparticles for Enhanced Inhibition of Respiratory Syncytial Virus-Induced Pneumonia as an Alternative Therapy","authors":"Lizhen Yuan,&nbsp;Zhaowen Wang","doi":"10.1007/s12247-026-11114-8","DOIUrl":"10.1007/s12247-026-11114-8","url":null,"abstract":"<div><p>Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infection requiring hospitalization in children worldwide. Although no combination therapies exist for RSV, ribavirin (RBA) and TMC353121 (TMC) can efficiently combat RSV through different mechanisms. We investigated the feasibility of formulating RBA and TMC into an RBA-TMC self-assembled nanoparticle (RTSN) and assessed its antiviral activity. Our results showed that RBA and TMC formed RTSN through hydrogen bonding and π-π stacking interactions. Cellular studies indicated that RTSN exhibited remarkable antioxidant, antiviral, and anti-inflammatory properties. RTSN showed antiviral efficacy, with a selectivity index of 43.8 and an effective concentration (EC₅₀) of 10.9 µM. Moreover, RTSN was used to treat a mouse model of the respiratory syncytial virus-induced pneumonia (RSVIP) via multiple mechanisms, including mitigating oxidative stress, reducing viral load, and modulating macrophage polarization, while maintaining promising biosafety. Overall, this study presents an innovative treatment strategy for RSV and highlights the benefits of self-assembly technology in augmenting potential.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149339223","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":"AQbD-Based HPLC Method Development, LC-MS/MS Characterization, and Bivariate Conformity Assessment for Estradiol Valerate and Norethisterone Enanthate in Injectable Contraceptives","authors":"Bárbara Ramos da Silva,&nbsp;Fabiane Dörr,&nbsp;Felipe Rebello Lourenço","doi":"10.1007/s12247-026-11137-1","DOIUrl":"10.1007/s12247-026-11137-1","url":null,"abstract":"<div><p>This study aimed to develop and validate an Analytical Quality by Design (AQbD)-based HPLC method for the simultaneous determination of estradiol valerate (EV) and norethisterone enanthate (NE) in injectable contraceptives, integrating LC–MS/MS characterization of degradation products, measurement uncertainty, and bivariate conformity assessment. Chromatographic conditions were systematically investigated using experimental design and statistical modeling, followed by validation according to ICH Q2(R2). Forced degradation studies were used to evaluate chromatographic selectivity toward degradation products, and major degradation products were characterized by LC–MS/MS. The optimized method showed satisfactory linearity (r² ≥ 0.9938), precision (RSD ≤ 3.0%), and accuracy (mean recoveries of 98.4–101.6%). Combined standard uncertainties were 2.1% for NE and 2.3% for EV. Incorporating these uncertainties into conformity assessment showed that conventional univariate guard-bands controlling the risk for each analyte individually may not adequately control the overall risk when both active ingredients are assessed simultaneously. A bivariate guard-band approach therefore provided more restrictive acceptance regions to maintain the total consumer’s risk at approximately 5%. The main contribution of this study is the integration of AQbD-based analytical development, degradation-product characterization, measurement uncertainty, and multiparametric decision rules within a single analytical framework. This strategy extends analytical validation beyond conventional performance assessment and provides a risk-based basis for conformity decisions in multicomponent pharmaceutical products.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12247-026-11137-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149339222","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":"Development and Characterization of Hyaluronic Acid-Functionalized Docetaxel-Loaded Cubosomes for Targeted Breast Cancer Treatment","authors":"Nitish Kumar,&nbsp;Anupama Panday,&nbsp;Nitin Gautam,&nbsp;Sree Prakash Pandey,&nbsp;Dharmendra Kumar,&nbsp;Avadh Biharee,&nbsp;Akhlesh Kumar Jain","doi":"10.1007/s12247-026-11136-2","DOIUrl":"10.1007/s12247-026-11136-2","url":null,"abstract":"<div><h3>Purpose</h3><p>Breast cancer remains a major global health burden, and the clinical utility of docetaxel is frequently compromised by poor aqueous solubility, non-specific biodistribution, and dose-limiting systemic toxicity. The present study aimed to develop and optimize hyaluronic acid (HA)-conjugated docetaxel-loaded cubosomes for targeted breast cancer therapy.</p><h3>Methods</h3><p>Docetaxel-loaded cubosomes were optimized using a three-factor, three-level Box–Behnken design. The optimized formulation was coated with chitosan and hyaluronic acid to obtain HA-conjugated cubosomes. The developed cubosomes were characterized for particle size, zeta potential, entrapment efficiency, Fourier transform infrared spectroscopy, scanning electron microscopy, in vitro drug release, stability, and cytotoxicity against MCF-7 breast cancer cells using the MTT assay.</p><h3>Results</h3><p>The optimized docetaxel-loaded cubosomes exhibited a particle size of 156.23 ± 1.44 nm, PDI of 0.25 ± 0.05, and entrapment efficiency of 88.48 ± 1.35%. Following HA functionalization, the particle size increased to 194.62 ± 3.72 nm, with a shift in zeta potential to − 27.4 mV, supporting surface modification. HA-conjugated cubosomes demonstrated a prolonged drug release profile, with approximately 70.8% docetaxel release after 24 h at pH 7.4 compared with 89.1% from unconjugated cubosomes. At pH 5.5, approximately 85% and 94% drug release were observed from HA-conjugated and unconjugated cubosomes, respectively. The release profiles predominantly followed the Higuchi model at both pH conditions. In the MTT assay, the IC₅₀ values were 0.47 µM for HA-conjugated cubosomes and 0.53 µM for unconjugated cubosomes. At 20 µM HA-conjugated cubosomes produced 85% cell death compared with 70% for unconjugated cubosomes. The formulation remained stable under refrigerated conditions for three months.</p><h3>Conclusion</h3><p>HA-conjugated cubosomes represent a promising targeted nanocarrier for breast cancer treatment by combining sustained drug release with enhanced tumor cytotoxicity, thereby improving the anticancer efficacy of docetaxel and offering potential for future translational applications. Further investigations involving in vivo pharmacokinetic, biodistribution, and antitumor efficacy studies are currently envisaged as a part of another study to validate the translational potential of the developed nanocarrier.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"22 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149338628","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}