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Formulation and Comparative Characterization of SLNs and NLCs for Targeted Co-Delivery of Paclitaxel and Hydroxytyrosol Carboxylic Acid Esters Against Triple-Negative Breast Cancer. 靶向递送紫杉醇和羟基酪醇羧酸酯治疗三阴性乳腺癌的sln和NLCs的制备和比较表征
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-16 DOI: 10.3390/pharmaceutics17091208
Elena Peira, Simona Sapino, Daniela Chirio, Fabio Bucciol, Flavia Turku, Emanuela Calcio Gaudino, Giancarlo Cravotto, Chiara Riganti, Marina Gallarate
{"title":"Formulation and Comparative Characterization of SLNs and NLCs for Targeted Co-Delivery of Paclitaxel and Hydroxytyrosol Carboxylic Acid Esters Against Triple-Negative Breast Cancer.","authors":"Elena Peira, Simona Sapino, Daniela Chirio, Fabio Bucciol, Flavia Turku, Emanuela Calcio Gaudino, Giancarlo Cravotto, Chiara Riganti, Marina Gallarate","doi":"10.3390/pharmaceutics17091208","DOIUrl":"10.3390/pharmaceutics17091208","url":null,"abstract":"<p><p><b>Background:</b> The management of triple-negative breast cancer (TNBC) remains a therapeutic challenge due to the presence of multidrug resistance (MDR) and hypoxia-induced chemoresistance, both of which substantially reduce the efficacy of conventional chemotherapy. Although certain natural compounds have shown the ability to modulate these resistance mechanisms, their clinical application is hindered by poor solubility and limited bioavailability. Among such phenolic compounds, 7-hydroxytyrosol (HTyr)-a phenolic compound from olive oil and olive leaves-has been reported to modulate hypoxia-inducible factor-1 (HIF-1). <b>Methods:</b> In this study, we developed hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the targeted and synergistic co-delivery of paclitaxel (PTX) and hydroxytyrosol carboxylic acid esters (C<sub>n</sub>-HTyrCA), precursors that share the antioxidant biphenolic moiety with HTyr. <b>Results:</b> Among the formulations tested, SLNs of trilaurin (TL) exhibited the highest entrapment efficiency (EE%), optimal average particle size, Zeta potential, and good colloidal stability. Of the synthesized C<sub>n</sub>-HTyrCA derivatives, C<sub>8</sub>- and C<sub>10</sub>-HTyrCA showed superior loading capacity. In vitro release profiles indicated a sustained drug release pattern for both nanoparticles. HA decoration led to a marked increase in particle size and induced a shift in surface charge, confirming successful decoration and suggesting enhanced targeting potential via HA-CD44 interaction. Cytotoxicity assays conducted on MDA-MB-231 cells showed that PTX-loaded TL-SLNs exerted enhanced antitumor activity, particularly when HA-decorated, and a synergistic effect was observed upon co-administration with SLNs loaded with C<sub>8</sub>-HTyrCA. <b>Conclusions:</b> Overall, our findings support the potential of SLN as a promising strategy to overcome key resistance mechanisms in TNBC, enabling reduced chemotherapeutic dosing and improving therapeutic outcomes.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pancreatic Cancer-Targeting Cascade Nanoamplifier Enables Self-Replenishing H2O2 Generation and Autophagy Disruption in Chemodynamic Therapy. 胰腺癌靶向级联纳米放大器在化学动力学治疗中实现H2O2的自我补充和自噬破坏。
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-16 DOI: 10.3390/pharmaceutics17091201
Jiaqi Yu, Lishuai Feng, Yunpeng Tang, Nianhui Yu, Jianning Lin, Yuan Ji, Hui Li
{"title":"Pancreatic Cancer-Targeting Cascade Nanoamplifier Enables Self-Replenishing H<sub>2</sub>O<sub>2</sub> Generation and Autophagy Disruption in Chemodynamic Therapy.","authors":"Jiaqi Yu, Lishuai Feng, Yunpeng Tang, Nianhui Yu, Jianning Lin, Yuan Ji, Hui Li","doi":"10.3390/pharmaceutics17091201","DOIUrl":"10.3390/pharmaceutics17091201","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Conventional therapeutic strategies exhibit limited efficacy against pancreatic cancer, primarily due to its profoundly hypoxic tumor microenvironment and dense fibrotic stroma. Chemodynamic therapy (CDT) holds promise; however, its application in pancreatic cancer is restricted by insufficient endogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) levels and the activation of protective autophagy in response to oxidative stress. <b>Methods:</b> To overcome these obstacles, we developed a tumor microenvironment-responsive, pancreatic cancer-targeted CDT nanoamplifier-H-MnO<sub>2</sub>/GOX&CQ-iRGD-comprising a hollow mesoporous MnO<sub>2</sub> shell co-loaded with glucose oxidase (GOX) and chloroquine (CQ), and surface-functionalized with the tumor-penetrating peptide iRGD. GOX catalyzes glucose oxidation to generate H<sub>2</sub>O<sub>2</sub>, enhancing Fenton-like reactions. CQ suppresses autophagy induced by oxidative stress, thereby alleviating therapy resistance. The iRGD peptide targets integrin α<sub>v</sub>β<sub>3</sub>, which is overexpressed on pancreatic cancer cells and tumor vasculature, promoting deep tumor penetration and enhanced delivery efficiency. <b>Results:</b> We comprehensively characterized the nanoplatform's physicochemical properties, tumor microenvironment triggered degradation, controlled drug release, glucose-driven H<sub>2</sub>O<sub>2</sub> generation, and hydroxyl radical production in vitro. Cellular studies assessed nanoparticle uptake, intracellular H<sub>2</sub>O<sub>2</sub> production, autophagy inhibition, and cytotoxicity. In vivo experiments further demonstrated effective tumor targeting and significant therapeutic outcomes in pancreatic cancer models. <b>Conclusions:</b> This nanoplatform addresses major barriers of CDT-namely, insufficient H<sub>2</sub>O<sub>2</sub> levels, autophagy-mediated resistance, and limited intratumoral penetration-offering a promising strategy for pancreatic cancer treatment.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic Potential of Wogonin-Aloperine Co-Amorphous for Oral Squamous Cell Carcinoma. 沃贡-丙operine共无定形治疗口腔鳞状细胞癌的潜力。
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-16 DOI: 10.3390/pharmaceutics17091204
Guoliang Wu, Han Li, Zhongshui Xie, Song Ni, Yiming Zhu, Chunxue Jia, Chenyu Pan, Shaoyan Liu, Hongjuan Wang
{"title":"Therapeutic Potential of Wogonin-Aloperine Co-Amorphous for Oral Squamous Cell Carcinoma.","authors":"Guoliang Wu, Han Li, Zhongshui Xie, Song Ni, Yiming Zhu, Chunxue Jia, Chenyu Pan, Shaoyan Liu, Hongjuan Wang","doi":"10.3390/pharmaceutics17091204","DOIUrl":"10.3390/pharmaceutics17091204","url":null,"abstract":"<p><p><b>Background</b>: Oral squamous cell carcinoma (OSCC) is a major epithelial malignancy of the head and neck with high morbidity and mortality. The conventional antineoplastic medications used in clinical practice have become less effective due to the heterogeneity of tumors, accompanied by severe side effects. Therefore, the development of novel chemotherapeutic agents has become an important goal of anti-OSCC therapy. <b>Methods</b>: Our group has previously developed a novel wogonin-aloperine co-amorphous (Wog-Alop). In this study, the anti-OSCC efficacy of Wog-Alop was evaluated by a patient-derived tumor xenograft (PDX) model. Subsequently, network pharmacology was employed to predict the key targets of Wog-Alop on OSCC, and the predicted key targets were further confirmed by Western blot and immunochemistry. <b>Results</b>: The results revealed that Wog-Alop manifests the higher efficacy in inhibition of OSCC proliferation by regulating the expression of the key targets, Bcl-2, Bax, P53, and Caspase3, implying that the apoptotic mechanism is implicated in Wog-Alop-induced inhibition of proliferation in OSCC. <b>Conclusions</b>: Collectively, the present work demonstrated anti-OSCC bioactivity of Wog-Alop, suggesting that Wog-Alop could be developed as an innovative therapeutic agent for OSCC therapy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Pilot, Randomised, Placebo-Controlled, Double-Blind Trial of a Single Oral Dose of Ivermectin for Post-Exposure Prophylaxis of SARS-CoV-2. 一项单剂量口服伊维菌素用于SARS-CoV-2暴露后预防的随机、安慰剂对照、双盲试验
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-16 DOI: 10.3390/pharmaceutics17091205
Kylie M Wagstaff, Mark S Stein, Alan Herschtal, Jean-Jacques Rajter, Juliana Cepelowicz Rajter, Michele Sallaberger, Alexia Smileski, Amala Kanagalingam, David A Jans
{"title":"A Pilot, Randomised, Placebo-Controlled, Double-Blind Trial of a Single Oral Dose of Ivermectin for Post-Exposure Prophylaxis of SARS-CoV-2.","authors":"Kylie M Wagstaff, Mark S Stein, Alan Herschtal, Jean-Jacques Rajter, Juliana Cepelowicz Rajter, Michele Sallaberger, Alexia Smileski, Amala Kanagalingam, David A Jans","doi":"10.3390/pharmaceutics17091205","DOIUrl":"10.3390/pharmaceutics17091205","url":null,"abstract":"<p><p><b>Background:</b> The efficacy of a single oral dose of Ivermectin as prophylaxis for SARS-CoV-2 is uncertain. This trial sought to evaluate the effectiveness of a single oral low dose of Ivermectin to prevent SARS-CoV-2 infection or reduce symptoms if infection did occur. <b>Methods:</b> Asymptomatic community-dwelling adults were enrolled in this study within 72 h of close contact with a case of SARS-CoV-2. Participants were randomised, stratified by vaccination status and exposure site, to a single oral 200 µg/kg dose of Ivermectin or placebo. The primary outcome was conversion to a positive polymerase chain reaction (PCR) or rapid antigen test (RAT) for SARS-CoV-2 within 14 days of close contact. Secondary outcomes were restricted to those who met the primary outcome. They included the following: days alive free of symptoms in the 14 (DAFS1-14) and 28 (DAFS1-28) days following intervention and days from close contact until a positive PCR or RAT for SARS-CoV-2. <b>Results:</b> A total of 536 participants registered for this trial. Of these, 86 met inclusion criteria and were randomised. 68 adhered to the trial protocol and were included in the analysis. A total of 11/36 (Ivermectin arm) and 11/32 (placebo arm) met the primary outcome. After controlling for age and prior SARS-CoV-2 infection, the estimate (95% confidence interval (95% CI)) of the effect of Ivermectin (compared to placebo) on the absolute value of the proportion of participants converting to a positive PCR or RAT was -0.051 (-0.26 to 0.16), <i>p</i> = 0.63. After controlling for prior SARS-CoV-2 infection, age, body mass index, hypertension and lung disease, the average treatment effect (Ivermectin versus placebo) on DAFS1-14 was 2.5 days (95%CI 1.1 to 4.5), <i>p</i> = 0.036, and for DAFS1-28, was 2.3 days (95% CI 0.7 to 3.3), <i>p</i> = 0.35. The mean (standard deviation) number of days from close contact until a positive PCR or RAT was 5.0 (4.1) days for the Ivermectin group versus 2.6 (0.8) days for the placebo group. After controlling for age and prior SARS-CoV-2 infection, the average treatment effect (95%CI), Ivermectin versus placebo, on days from close contact until a positive PCR or RAT was 2.3 days (95% CI 1.1 to 3.4), <i>p</i> = 0.033. <b>Conclusions:</b> We did not demonstrate that a single oral low dose of Ivermectin administered to asymptomatic adults within 72 h of close contact with a case of SARS-CoV-2 prevents conversion to a positive PCR or RAT. However, the trial had a small sample size and does not exclude a clinically meaningful effect of Ivermectin on conversion to a positive PCR or RAT. Amongst those who did convert to a positive PCR or RAT, the use of Ivermectin significantly lengthened the time from close contact to conversion and increased the number of days alive free of symptoms following intervention.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
BaTiO3 Nanocarriers: Advancing Targeted Therapies with Smart Drug Release. BaTiO3纳米载体:推进药物智能释放靶向治疗。
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-16 DOI: 10.3390/pharmaceutics17091203
Milica Ćurčić, Branka Hadžić, Martina Gilić, Zorica Lazarević, Andjelija Ilić
{"title":"BaTiO<sub>3</sub> Nanocarriers: Advancing Targeted Therapies with Smart Drug Release.","authors":"Milica Ćurčić, Branka Hadžić, Martina Gilić, Zorica Lazarević, Andjelija Ilić","doi":"10.3390/pharmaceutics17091203","DOIUrl":"10.3390/pharmaceutics17091203","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Barium titanate (BaTiO<sub>3</sub>)-based nanocarriers have emerged as versatile and promising platforms for targeted drug delivery, owing to their unique combination of biocompatibility, piezoelectric and ferroelectric properties, as well as responsiveness to external stimuli. These multifunctional ceramic nanoparticles can be precisely engineered to enable spatiotemporally controlled release of therapeutic agents, triggered by physical stimuli such as ultrasound, light, magnetic fields, temperature changes, and pH variations. Such an approach enhances treatment efficacy while reducing systemic side effects. <b>Methods</b>: This review provides a comprehensive overview of the latest advancements in the development and biomedical application of BaTiO<sub>3</sub>-based nanocarriers. Special emphasis is placed on modern synthesis strategies, surface functionalization methods, and the integration of BaTiO<sub>3</sub> with other functional nanomaterials to create hybrid systems with improved therapeutic performance. Key challenges in clinical translation are also discussed, including biocompatibility assessment, biodistribution, and regulatory requirements. <b>Conclusions</b>: BaTiO<sub>3</sub>-based nanocarriers show promise as materials well suited for advanced biomedical applications. The paper concludes with an outline of future research directions aimed at optimizing these advanced nanosystems for precision and personalized medicine, with applications in oncology, anti-infective therapy, and regenerative medicine.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Applications of PBPK Modeling to Estimate Drug Metabolism and Related ADME Processes in Specific Populations. PBPK模型在特定人群中估计药物代谢和相关ADME过程中的应用。
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-16 DOI: 10.3390/pharmaceutics17091207
Pavani Gonnabathula, Miao Li, Suresh K Nagumalli, Darshan Mehta, Kiara Fairman
{"title":"Applications of PBPK Modeling to Estimate Drug Metabolism and Related ADME Processes in Specific Populations.","authors":"Pavani Gonnabathula, Miao Li, Suresh K Nagumalli, Darshan Mehta, Kiara Fairman","doi":"10.3390/pharmaceutics17091207","DOIUrl":"10.3390/pharmaceutics17091207","url":null,"abstract":"<p><p><b>Background:</b> Physiologically based pharmacokinetic (PBPK) models utilize computer-based simulations to predict the pharmacokinetics of drugs. By using mathematical modeling techniques consisting of differential equations to simulate blood flow, tissue compositions, and organ properties, the pharmacokinetic properties of drugs can be better understood. Specifically, PBPK models can provide predictive information about drug absorption, distribution, metabolism, and excretion (ADME). The information gained from PBPK models can be useful in both drug discovery, development, and regulatory science. PBPK models can help to address some of the ethical dilemmas that arise during the drug development process, particularly when examining patient populations where testing a new drug may have significant ethical concerns. Patient populations where significant physiological change (i.e., pregnancy, pediatrics, geriatrics, organ impairment populations, etc.) and pathophysiological influences resulting in PK changes can also benefit from PBPK modeling. Additionally, PBPK models can be utilized to predict variations in drug metabolism resulting from genetic polymorphisms, age, and disease states. <b>Methods:</b> In this mini-review, we examine the various applications of PBPK models in drug metabolism. Current research articles related to drug metabolism in genetics, life-stages, and disease states were reviewed. <b>Results:</b> Several key factors in genetics, life-stage, and disease states that affect metabolism in PBPK models are identified. In genetics, the role of CYP enzymes, genetic polymorphisms, and ethnicity may influence metabolism. Metabolism generally changes over time from neonate, pediatric, adult, geriatric, and perinatal populations. Disease states such as renal and hepatic impairment, weight and other acute and chronic diseases also can also alter metabolism. Several examples of PBPK models applying these physiological changes have been published. <b>Conclusions:</b> The utilization and recognition of these specific areas in PBPK modeling can aid in personalized dosing strategy, clinical trial optimization, and regulatory submission.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Hasan et al. Nitric Oxide-Releasing Bacterial Cellulose/Chitosan Crosslinked Hydrogels for the Treatment of Polymicrobial Wound Infections. Pharmaceutics 2022, 14, 22. 更正:Hasan等人。一氧化氮释放细菌纤维素/壳聚糖交联水凝胶治疗多微生物伤口感染。医药科学,2022,14,22。
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-16 DOI: 10.3390/pharmaceutics17091206
Nurhasni Hasan, Juho Lee, Hye-Jin Ahn, Wook Ryol Hwang, Muhammad Akbar Bahar, Habibie Habibie, Muhammad Nur Amir, Subehan Lallo, Hong-Joo Son, Jin-Wook Yoo
{"title":"Correction: Hasan et al. Nitric Oxide-Releasing Bacterial Cellulose/Chitosan Crosslinked Hydrogels for the Treatment of Polymicrobial Wound Infections. <i>Pharmaceutics</i> 2022, <i>14</i>, 22.","authors":"Nurhasni Hasan, Juho Lee, Hye-Jin Ahn, Wook Ryol Hwang, Muhammad Akbar Bahar, Habibie Habibie, Muhammad Nur Amir, Subehan Lallo, Hong-Joo Son, Jin-Wook Yoo","doi":"10.3390/pharmaceutics17091206","DOIUrl":"10.3390/pharmaceutics17091206","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Formulation, Optimization, and Evaluation of Transferosomes Co-Loaded with Methotrexate and Sorafenib for Anti-Arthritic Activity. 甲氨蝶呤和索拉非尼共载转移体抗关节炎活性的配方、优化和评价。
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-15 DOI: 10.3390/pharmaceutics17091196
Muhammad Adnan, Lateef Ahmad, Muhammad Junaid Dar, Humzah Jamshaid, Muhammad Noman, Muhammad Faheem
{"title":"Formulation, Optimization, and Evaluation of Transferosomes Co-Loaded with Methotrexate and Sorafenib for Anti-Arthritic Activity.","authors":"Muhammad Adnan, Lateef Ahmad, Muhammad Junaid Dar, Humzah Jamshaid, Muhammad Noman, Muhammad Faheem","doi":"10.3390/pharmaceutics17091196","DOIUrl":"10.3390/pharmaceutics17091196","url":null,"abstract":"<p><p><b>Purpose:</b> This study was designed to develop a nanoparticle-based methotrexate (MTX) and sorafenib (SRF)-loaded transferosome (MTX-SRF-TFS) for effective management of arthritis through the transdermal route. <b>Methods:</b> For the preparation of MTX-SRF-TFS, the thin-film hydration technique was selected and optimized using Box-Behnken Design. The particle size of the nanoparticles was determined using a Malvern Zeta sizer and electron microscopy. An in vivo skin retention and penetration study was also conducted to evaluate the designed delivery system. Furthermore, the therapeutic response of MTX-SRF-TFS was determined using the CFA-induced mouse model. <b>Results:</b> The optimized MTX-SRF-TFS formulation (F4), having an average particle size (PS) of 162.20 ± 2.89 nm and percent entrapment efficiency (%EE) of MTX and SRF of 92.16 ± 4.95 and 81.54 ± 3.23, respectively, was selected for further assessment. Due to the deformable nature of MTX-SRF-TFS, MTX and SRF penetrate more deeply into the cutaneous layers, exhibiting an enhanced transdermal effect, as shown by the results of ex vivo skin permeation and retention studies. Furthermore, in vivo anti-arthritic studies have shown the superior pharmacodynamic response of MTX and SRF when incorporated into transferosomes, as it caused a marked reduction in arthritic score and paw diameter in CFA-induced arthritis in BALB/c mice. Histopathology analysis and X-ray radiography also confirmed the findings that MTX-SRF-TFS has improved anti-arthritic response in contrast to plain MTX-SRF gel. <b>Conclusions:</b> The MTX-SRF-TFS is highly effective in managing CFA-induced arthritis, and the designed delivery system should be further evaluated on pharmacokinetic grounds to progress towards clinical studies.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In-Depth Understanding of the Impact of Material Properties on the Performance of Jet Milling of Active Pharmaceutical Ingredients. 深入了解物料性质对有效药物成分射流研磨性能的影响。
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-15 DOI: 10.3390/pharmaceutics17091197
Viktor Bultereys, Kensaku Matsunami, Laure Descamps, Roel Mertens, Alain Collas, Ashish Kumar
{"title":"In-Depth Understanding of the Impact of Material Properties on the Performance of Jet Milling of Active Pharmaceutical Ingredients.","authors":"Viktor Bultereys, Kensaku Matsunami, Laure Descamps, Roel Mertens, Alain Collas, Ashish Kumar","doi":"10.3390/pharmaceutics17091197","DOIUrl":"10.3390/pharmaceutics17091197","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Among different milling techniques, spiral air jet milling can produce finer particles without the use of solvents or additives, thereby improving the bioavailability and content uniformity of the final dosage form. However, milling can complicate downstream processability of active pharmaceutical ingredients (APIs) due to reduced bulk powder flowability and post-milling lump formation. Process settings are often optimized only for particle size reduction, without sufficient consideration of manufacturability, largely because of limited API availability and a lack of knowledge about influential material properties. This study aimed to investigate the impact of material properties and process settings on milling performance and downstream manufacturability. <b>Methods:</b> Four APIs, examined in a total of eight grades, were characterized for their bulk mechanical properties and compression energy parameters using a compaction simulator. These grades were subjected to milling experiments within a design-of-experiments framework. Statistical analyses were performed, and population balance models (PBMs) were developed and calibrated for each experiment to link material properties and process settings to milling outcomes. <b>Results:</b> A higher gas flow rate was identified as the most significant contributor to particle size reduction. The influence of mechanical properties, particularly Young's modulus and Poisson's ratio, was evident and correlated with unmilled particle sizes. PBM analyses showed that a higher gas feed rate decreased the critical particle size for breakage, while intrinsic mechanical properties affected the breakage rate function. <b>Conclusions:</b> By integrating material properties and process settings into PBM analyses, specific breakage mechanisms could be identified. These findings provide a framework for optimizing jet milling not only for particle size reduction but also for downstream processability of APIs.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stimuli-Responsive Cationic Lyotropic Liquid Crystalline Nanoparticles: Formulation Process, Physicochemical and Morphological Evaluation. 刺激响应型阳离子溶性液晶纳米颗粒:配方、理化和形态学评价。
IF 5.5 3区 医学
Pharmaceutics Pub Date : 2025-09-15 DOI: 10.3390/pharmaceutics17091199
Maria Chountoulesi, Natassa Pippa, Varvara Chrysostomou, Aleksander Forys, Barbara Trzebicka, Stergios Pispas, Costas Demetzos
{"title":"Stimuli-Responsive Cationic Lyotropic Liquid Crystalline Nanoparticles: Formulation Process, Physicochemical and Morphological Evaluation.","authors":"Maria Chountoulesi, Natassa Pippa, Varvara Chrysostomou, Aleksander Forys, Barbara Trzebicka, Stergios Pispas, Costas Demetzos","doi":"10.3390/pharmaceutics17091199","DOIUrl":"10.3390/pharmaceutics17091199","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Lyotropic liquid crystalline nanoparticles are promising drug delivery nanocarriers, exhibiting significant technological advantages, such as their extended internal morphology. In this study, cationic non-lamellar lyotropic-lipidic liquid crystalline nanoparticles were formulated by phytantriol lipid. <b>Methods</b>: The poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) block copolymer carrying tri-phenyl-phosphine cations (TPP-QPDMAEMA-b-PLMA), was employed as a stabilizer co-assisted by other polymeric guests. The exact qualitative and quantitative formulation of the systems was investigated. Their physicochemical profile was depicted from a variety of light scattering techniques, while their microenvironmental parameters were determined by fluorescence spectroscopy using adequate probe molecules. The effect of environmental conditions was monitored, confirming stimuli-responsiveness properties. Their morphology was illustrated by cryo-TEM, revealing expanded internal assemblies. Resveratrol was incorporated into the nanoparticles and the entrapment efficiency was calculated. <b>Results</b>: Their properties were found to be dependent on the formulation characteristics, such as the lipid used, as well as the architecture of the polymeric stabilizer, also being found to be stealth toward proteins, exhibiting stimuli responsiveness and high entrapment efficiency. <b>Conclusions</b>: The studied liquid crystalline nanoparticles, being stimuli-responsive, with high cationic potential, high loading capacity and showing intriguing 3D structures, are suitable for pharmaceutical applications.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"17 9","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12473691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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