AAPS PharmSciTech最新文献_第3页

Human Serum Albumin-Lipid Nanocapsules of Duvelisib for Hematological Cancers: Characterization, In-Vitro Cell-Culture, Toxicity and Pharmacokinetic Studies 用于血液学癌症的人血清白蛋白脂质纳米胶囊：表征、体外细胞培养、毒性和药代动力学研究

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-15 DOI: 10.1208/s12249-025-03305-2

Srushti Mahajan, Mayur Aalhate, Anamika Sharma, Suman Karadagatla, Santosh Kumar Guru, Pankaj Kumar Singh

Hematological malignancies like leukemia and lymphoma are severe cancers with high relapse rates. Duvelisib (DUV) is a selective dual phosphatidylinositol 3-kinase-delta and gamma inhibitor with good potential for treating hematological malignancies. However, its application is subsided by poor solubility, permeability and side effects. Herein, we have designed a human serum albumin shell and liquid-lipid core type of nanocapsule system (DUV-NCs) for effective drug loading, enhanced circulation and improved anticancer potential of DUV. The DUV-NCs were extensively optimized with DoE, resulting in a mean particle size of 188.2 ± 1.1 nm, PDI of 0.238 ± 0.018 and entrapment efficiency of 86.99 ± 1.40%. Moreover, a sustained release behaviour with around 80% release up to 48 h was observed. DUV-NCs showed an IC₅₀ of (12.78 ± 0.66 µg/mL), which was significantly decreased (P < 0.001) than the free drug (IC₅₀: 26.08 ± 4.04 µg/mL) in the MOLT-4 cell line. Qualitative and quantitative cellular uptake studies in MOLT-4 cells revealed considerably higher internalization of FITC-NCs than free FITC. DUV-NC-treated groups also displayed higher ROS generation, which was also evident from the increase in apoptotic bodies in MOLT-4 cells. Pharmacokinetic studies showed a 2.07-fold increase in MRT with a 3.56-fold rise in AUC_0-t from DUV-NCs compared to free DUV. The DUV-NCs were found to be safe in toxicity studies with no major alterations in biomarkers compared to the control. In conclusion, DUV-NCs is a promising strategy to deliver DUV in hematological malignancies with improved efficacy and safety.

Graphical Abstract

血液恶性肿瘤如白血病和淋巴瘤是复发率高的严重癌症。Duvelisib （DUV）是一种选择性双磷脂酰肌醇3-激酶- δ和γ抑制剂，具有治疗血液系统恶性肿瘤的良好潜力。但其溶解度、渗透性差、副作用大，阻碍了其应用。在此，我们设计了一种人血清白蛋白外壳和液脂核型纳米胶囊系统（DUV- ncs），用于有效的药物装载，促进循环和提高DUV的抗癌潜力。利用DoE对DUV-NCs进行了广泛优化，得到的DUV-NCs平均粒径为188.2±1.1 nm， PDI为0.238±0.018，包封效率为86.99±1.40%。此外，在48小时内观察到约80%的持续释放行为。DUV-NCs的IC50为（12.78±0.66µg/mL），与游离药物（26.08±4.04µg/mL）相比显著降低（P < 0.001）。MOLT-4细胞的定性和定量细胞摄取研究显示，FITC- ncs的内在化程度明显高于游离FITC。duv - nc处理组也显示出更高的ROS生成，这也可以从MOLT-4细胞凋亡小体的增加中看出。药代动力学研究显示，与游离DUV相比，DUV- nc的MRT增加2.07倍，AUC0-t增加3.56倍。在毒性研究中发现，duv - nc是安全的，与对照组相比，生物标志物没有重大变化。总之，DUV- nc是一种很有前途的策略，可以在血液恶性肿瘤中提供DUV，具有更高的疗效和安全性。图形抽象

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引用次数: 0

Fabrication of Second-Generation Acalabrutinib Nanocrystals by Employing the Nano-Edge Method for Improving the Physico-Chemical Properties and Forecasting their In-Silico Pharmacokinetic Behaviour 利用纳米边缘法制备第二代阿卡拉替尼纳米晶体，改善其物理化学性质并预测其在硅中的药代动力学行为

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-15 DOI: 10.1208/s12249-025-03298-y

Bharath M, Ujala Gupta, Anish Dhuri, Tanmoy Kanp, Khushi Rode, Sharon Munagalasetty, Vasundhra Bhandari, Soumyadip Mukherjee, Arvind Gulbake, Pankaj Kumar Singh

Acalabrutinib (ACL) is approved by the USFDA and classified as a BCS class II drug, primarily used for treating chronic lymphocytic leukaemia. It is characterised by low solubility, particularly at higher pH levels, which results in reduced systemic absorption. Our current research aims to repurpose ACL for breast cancer treatment by enhancing its solubility and overall bioavailability through a second-generation nanocrystal formulation (SGACNCs). SGACNCs were prepared using the Nano-Edge method, which combines microprecipitation and high-pressure homogenization. The prepared SGACNCs with a mean particle size of 250.5 ± 17nm were characterised by solid-state techniques such as FTIR, DSC, PXRD, SEM, and BET analysis. In vitro dissolution studies indicated that at pH levels of 6.8 and 7.4, there was a 99 ± 0.2% and 99 ± 0.1% release after 6 h, respectively. Furthermore, the apparent permeability of the SGACNCs were observed to be two times greater than that of ACL. The stability studies indicated that the SGACNCs remained stable for 3 months at 5 ± 3 °C. Gastroplus 10.1 software was utilized to predict the pharmacokinetic profiles of SGACNCs based on their in vitro dissolution characteristics. In vitro biological studies on MDA-MB-231 cell lines showed a 1.55-fold reduction in IC₅₀ value in SGACNCs (36.08 ± 2.5 μM) compared to the ACL. SGACNCs showed higher cell internalisation, MMP depolarisation, ROS generation, apoptosis, reduced cell migration, and colony formation. The Nano-Edge technique for the nanonization of ACL showcased its potential to increase both the solubility and dissolution rate of ACL, which will boost its therapeutic efficacy in treating breast cancer.

Graphical Abstract

Acalabrutinib （ACL）获美国fda批准，被列为BCS II类药物，主要用于治疗慢性淋巴细胞白血病。它的特点是溶解度低，特别是在较高的pH水平下，这导致全身吸收减少。我们目前的研究旨在通过第二代纳米晶体配方（sacncs）提高其溶解度和整体生物利用度，从而将ACL重新用于乳腺癌治疗。采用微沉淀和高压均质相结合的纳米边缘法制备了sacncs。采用FTIR、DSC、PXRD、SEM、BET等固态技术对制备的sgarncs进行了表征，平均粒径为250.5±17nm。体外溶出度研究表明，在pH为6.8和7.4时，6 h释放度分别为99±0.2%和99±0.1%。此外，观察到sgacnc的表观通透性是ACL的两倍。稳定性研究表明，sacnc在5±3°C下保持稳定3个月。利用Gastroplus 10.1软件根据sacnc的体外溶出度特征预测其药动学特征。对MDA-MB-231细胞系的体外生物学研究表明，与ACL相比，sgacnc（36.08±2.5 μM）的IC50值降低了1.55倍。SGACNCs表现出更高的细胞内化、MMP去极化、ROS生成、凋亡、细胞迁移减少和集落形成。纳米边缘技术对前交叉韧带进行纳米化处理，可以提高前交叉韧带的溶解度和溶解速率，从而提高前交叉韧带治疗乳腺癌的疗效。图形抽象

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引用次数: 0

Challenges and Opportunities of Drug Delivery for Treatment of Alzheimer’s Disease 阿尔茨海默病药物递送治疗的挑战与机遇

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-15 DOI: 10.1208/s12249-025-03316-z

Marwa Adel Abd El-Fattah

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognitive functions. It represents a global health concern with increasing prevalence and devastating outcomes for the quality of life that could ultimately lead to death. AD is associated with deposition of β-amyloid (Aβ) plaques and intracellular buildup of tau proteins forming neurofibrillary tangles (NFTs), which are the main characteristics for AD brain tissues. Approved AD therapy is based mainly on symptomatic relief, and conventional medicaments often fail due to either low bioavailability, limited solubility, or failure to cross blood–brain barrier (BBB). The complexity in AD pathophysiology opens windows for many therapeutic options. So, lecanemab was recently approved by FDA as the first disease-modifying therapy. However, drug delivery to the brain remains challenging due to the nature of BBB. Hence, more extensive research is essential to develop disease-modifying therapies and also to find drug delivery strategies to ensure simplified administration and successful brain delivery. This review article summarizes AD pathogenesis with the corresponding treatment targets. It emphasizes innovative drug delivery strategies and novel formulation approaches to deliver medicines across BBB. The use of recent advancements in drug delivery to deliver medicaments across BBB are highlighted, with focus given to novel drug delivery systems and formulation of nanoparticles for brain targeting. The use of nutraceuticals, gene therapy, and stem cell therapy are is covered.

Graphical Abstract

阿尔茨海默病（AD）是一种以认知功能进行性恶化为特征的神经退行性疾病。它是一个全球性的健康问题，发病率越来越高，对生活质量造成毁灭性后果，最终可能导致死亡。AD与β-淀粉样蛋白（Aβ）斑块沉积和细胞内形成神经原纤维缠结（nft）的tau蛋白积聚有关，这是AD脑组织的主要特征。经批准的AD治疗主要基于症状缓解，而传统药物往往由于生物利用度低、溶解度有限或无法通过血脑屏障（BBB）而失败。阿尔茨海默病病理生理学的复杂性为许多治疗选择打开了窗口。因此，莱卡耐单抗最近被FDA批准为第一个疾病改善疗法。然而，由于血脑屏障的性质，药物递送到大脑仍然具有挑战性。因此，更广泛的研究对于开发疾病改善疗法和寻找药物递送策略以确保简化给药和成功的脑递送至关重要。本文就AD的发病机制及相应的治疗靶点进行综述。它强调创新的药物递送策略和新的配方方法，以跨血脑屏障递送药物。强调了在药物传递方面的最新进展，将药物传递到血脑屏障，重点是新的药物传递系统和脑靶向纳米颗粒的配方。包括营养药品、基因疗法和干细胞疗法的使用。图形抽象

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引用次数: 0

Preparation and Evaluation of Candesartan Cilexetil Solid Supersaturated Self-nanoemulsion Containing Phospholipids 含磷脂坎地沙坦西莱西酯固体过饱和自纳米乳的制备及评价

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-15 DOI: 10.1208/s12249-025-03307-0

Kai Zheng, Tianyi Wang, Hao Chen, Yuyang Zhao, Fucong Jia, Xinggang Yang

Candesartan cilexetil (CC) suffers from poor solubility, first-pass effect, and low bioavailability. In order to solve these problems, a solid supersaturated self-nanoemulsifying drug delivery system containing phospholipids (solid PC-S-SNEDDS) was constructed in this study. The system was based on the traditional self-nanoemulsifying drug delivery system (SNEDDS) with the addition of precipitation inhibitors, phospholipids and solid carriers to inhibit crystallisation, increase lymphatic transport, and facilitate transport and storage. SNEDDS, supersaturated self-nanoemulsifying drug delivery system (S-SNEDDS), supersaturated self-nanoemulsifying drug delivery system containing phospholipids (PC-S-SNEDDS), and solid PC-S-SNEDDS were prepared by central composite design and single factor investigation. The spectra of PXRD and FT-IR showed that the drugs in the solid PC-S-SNEDDS existed in an amorphous or molecular form and did not form new chemical bonds with the excipients. The results of dissolution experiments showed that compared with CC and marketed capsules, the four self-nanoemulsions could significantly increase the dissolution rate and cumulative dissolution of CC. The stability results demonstrate that the stability of the PC-S-SNEDDS was improved after curing. The results of pharmacokinetics in rats showed that the bioavailability of solid PC-S-SNEDDS was 568.17% and 415.00% of CC suspension and marketed capsules. In the lymphatic transport experiment, compared with CC suspension, solid PC-S-SNEDDS increased the proportion of lymphatic transport from 18.69% to 62.14%. The results showed that solid PC-S-SNEDDS improved the solubility, reduced the first-pass effect, and greatly improved the bioavailability of CC, which was a promising drug delivery system to solve the problem of CC.

Graphical Abstract

坎地沙坦西莱西酯（CC）存在溶解度差、首过效应和生物利用度低的问题。为了解决这些问题，本研究构建了含磷脂的固体过饱和自纳米乳化给药体系（solid PC-S-SNEDDS）。该系统以传统的自纳米乳化给药系统（SNEDDS）为基础，加入沉淀抑制剂、磷脂和固体载体，抑制结晶，增加淋巴运输，便于运输和储存。通过中心复合设计和单因素研究，制备了SNEDDS、过饱和自纳米乳化给药系统（S-SNEDDS）、含磷脂的过饱和自纳米乳化给药系统（PC-S-SNEDDS）和固体PC-S-SNEDDS。PXRD和FT-IR表明，固体PC-S-SNEDDS中的药物以无定形或分子形式存在，未与赋形剂形成新的化学键。溶出实验结果表明，与CC胶囊和市售胶囊相比，4种自纳米乳均能显著提高CC的溶出速率和累积溶出度，稳定性实验结果表明PC-S-SNEDDS固化后的稳定性得到改善。大鼠药代动力学结果表明，固体PC-S-SNEDDS的生物利用度分别为CC悬浮液和市售胶囊的568.17%和415.00%。在淋巴运输实验中，与CC悬浮液相比，固体PC-S-SNEDDS将淋巴运输比例从18.69%提高到62.14%。结果表明，固体PC-S-SNEDDS提高了CC的溶解度，降低了首过效应，大大提高了CC的生物利用度，是一种很有前途的解决CC问题的给药体系

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引用次数: 0

Implementing QbD for Nano-Pharmaceuticals and Complex Formulations to Achieve Predictable and High-Quality Outcomes 实施纳米药物和复杂制剂的QbD以获得可预测和高质量的结果

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-09 DOI: 10.1208/s12249-025-03308-z

Rohan Panwar, Anuradha Mishra, Abhisar Sahu, Syed Naved Quadri, M. Z. Abdin, Saman Fatima

Recent advances in artificial intelligence (AI) and machine learning (ML) are revolutionizing nanopharmaceutical development by enabling data-driven formulation design, process optimization, and prediction of biological performance. AI encompasses computational systems that mimic human cognitive functions, while ML utilizes large datasets to generate predictive models capable of managing complex pharmaceutical variables. Deep learning, a subset of ML, further refines this capability through multilayered neural networks that enhance decision-making and model precision. Integration of AI/ML into nanopharmaceutical research requires structured workflows encompassing data curation, cleaning, annotation verification, algorithm selection, and model validation to ensure reliability and reproducibility. In parallel, the pharmaceutical industry increasingly embraces the Quality by Design (QbD) framework to address raw material variability, limited process control, and incomplete understanding of critical formulation and process parameters. QbD provides a systematic, risk-based approach to embedding quality from the earliest development stages by defining Quality Target Product Profiles (QTPPs), identifying Critical Quality Attributes (CQAs), and controlling Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs). The convergence of AI/ML with QbD principles holds transformative potential for nanopharmaceuticals by enhancing predictive accuracy, minimizing experimental burden, and ensuring consistent, safe, and high-quality products. This review critically examines this integration, explores regulatory perspectives, and highlights current applications, challenges, and opportunities, offering a roadmap for efficient development, clinical translation, and commercialization of robust nanopharmaceutical formulations.

Graphical Abstract

人工智能（AI）和机器学习（ML）的最新进展通过实现数据驱动的配方设计，工艺优化和生物性能预测，正在彻底改变纳米药物开发。人工智能包括模拟人类认知功能的计算系统，而机器学习利用大型数据集生成能够管理复杂药物变量的预测模型。深度学习是机器学习的一个子集，通过多层神经网络进一步完善这种能力，从而提高决策和模型精度。将AI/ML集成到纳米制药研究中需要结构化的工作流程，包括数据管理、清理、注释验证、算法选择和模型验证，以确保可靠性和可重复性。与此同时，制药行业越来越多地采用设计质量（QbD）框架来解决原料可变性、有限的工艺控制以及对关键配方和工艺参数的不完全理解。QbD通过定义质量目标产品概要（QTPPs）、识别关键质量属性（cqa）、控制关键材料属性（cma）和关键工艺参数（CPPs），为从最早的开发阶段嵌入质量提供了一个系统的、基于风险的方法。AI/ML与QbD原则的融合通过提高预测准确性、减少实验负担和确保一致、安全和高质量的产品，为纳米药物带来了变革潜力。这篇综述批判性地审视了这种整合，探讨了监管观点，并强调了当前的应用、挑战和机遇，为高效开发、临床转化和强大的纳米药物配方的商业化提供了路线图。图形抽象

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引用次数: 0

Admixture Compatibility Studies in Parenteral Formulations: Packaging, Device, and Regulatory Perspectives 外用制剂中的外加剂相容性研究：包装、设备和监管观点

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-09 DOI: 10.1208/s12249-025-03315-0

Chetana Eknure, Vishvesh Joshi, Yogeshwar Bachhav

Parenteral therapies are vital in critical care, oncology, and nutrition, offering rapid onset, precise dosing, and high bioavailability. However, their safety is often compromised by admixture incompatibilities and drug-device interactions that threaten stability, efficacy, and patient outcomes. This review synthesizes the current scientific understanding of physicochemical and material-based incompatibilities in reconstituted formulations, intravenous drug admixtures, and parenteral nutrition, highlighting their implications for safety and efficacy. Key risks include precipitation, pH shifts, phase separation, leachables, particulates, and adsorption, with documented links to treatment failure, infusion reactions, and product recalls. Interactions with packaging systems-glass, plastics, elastomers, and siliconized components-are critically examined, alongside regulatory requirements for extractables, leachables, and container–closure integrity. Emerging strategies, such as advanced packaging materials, fluoropolymer-coated elastomers, and real-time monitoring technologies, are highlighted as pathways to safer parenteral therapy. By uniting clinical insights with regulatory requirements and emerging technologies, this review highlights admixture compatibility studies as essential to ensuring the safety, efficacy, and reliability of parenteral drug delivery.

Graphical Abstract

肠外治疗在重症监护、肿瘤学和营养学中至关重要，具有快速起效、精确给药和高生物利用度的特点。然而，它们的安全性经常受到混合物不相容和药物-装置相互作用的影响，从而威胁到稳定性、有效性和患者预后。这篇综述综合了目前对重组配方、静脉内药物混合物和肠外营养中物理化学和材料不相容的科学理解，强调了它们对安全性和有效性的影响。主要风险包括沉淀、pH值变化、相分离、可浸出物、颗粒和吸附，与治疗失败、输液反应和产品召回有记录的联系。与包装系统的相互作用-玻璃，塑料，弹性体和硅化组件-严格检查，以及可提取物，可浸出物和容器封闭完整性的监管要求。新兴战略，如先进的包装材料、含氟聚合物涂层弹性体和实时监测技术，被强调为更安全的肠外治疗途径。通过将临床见解与监管要求和新兴技术结合起来，本综述强调了混合物相容性研究对于确保肠外给药的安全性、有效性和可靠性至关重要。图形抽象

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引用次数: 0

Pharmacokinetics of Inhaled Clofazimine Dry Powder in Healthy Mice 吸入氯法齐明干粉在健康小鼠体内的药动学

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-09 DOI: 10.1208/s12249-025-03301-6

Prachi Agrawal, Kinnari Arte, Justin A. Tolman

Clofazimine (CFZ), an old and highly lipophilic antimycobacterial drug, is a second-line agent for the treatment of multi-drug-resistant tuberculosis (MDR-TB) and has demonstrated antitubercular efficacy when administered to the lung as different inhalation dry powder formulations. While its efficacy has been established, consensus has not been identified regarding the lung dose, pharmacokinetic (PK) properties, and biodistribution following inhalation. This study aimed to establish the biodistribution and inhaled PK of CFZ dry powder inhalation (DPI) formulation after single and multiple doses in healthy mice. Following a single low or high inhaled dose in healthy mice, lung concentrations of CFZ were ~ 20 folds higher than the corresponding plasma concentrations. Administering eight consecutive inhaled doses (twice weekly) maintained high and sustained lung concentrations (28 to 69 times higher than plasma concentrations), remaining significantly above the minimum inhibitory concentration (MIC: 0.6 – 2.0 μg/mL) of the free drug. Notably, CFZ concentrations in the lungs and plasma showed no discernable elimination phase up to four weeks post-dosing, with prolonged retention. Biodistribution studies indicated preferential CFZ retention in lung and spleen tissue following both single and multiple inhaled doses. In conclusion, these results suggest the novel dry powder inhaled CFZ formulation can produce high therapeutic concentration in lung tissues for extended periods of time after single and multiple doses, thereby, underscoring the potential of using inhaled CFZ as the treatment of MDR-TB.

Graphical Abstract

氯法齐明（CFZ）是一种古老的高度亲脂性抗细菌药物，是治疗耐多药结核病（MDR-TB）的二线药物，作为不同的吸入干粉制剂给予肺部时已显示出抗结核疗效。虽然其疗效已确定，但尚未就吸入后的肺剂量、药代动力学（PK）特性和生物分布达成共识。本研究旨在建立CFZ干粉吸入制剂单次和多次给药后在健康小鼠体内的生物分布和吸入PK。健康小鼠单次低剂量或高剂量吸入后，CFZ的肺浓度比相应的血浆浓度高约20倍。连续8次吸入剂量（每周2次）保持了高且持续的肺浓度（比血浆浓度高28 - 69倍），显著高于游离药物的最低抑制浓度（MIC: 0.6 - 2.0 μg/mL）。值得注意的是，肺和血浆中的CFZ浓度在给药后4周内没有明显的消除期，保留时间延长。生物分布研究表明，在单次和多次吸入剂量后，CFZ在肺和脾组织中都有优先保留。综上所述，这些结果表明，新型干粉吸入型CFZ制剂在单次和多次给药后可在肺组织中产生较长时间的高治疗浓度，从而强调了使用吸入型CFZ治疗耐多药结核病的潜力。图形抽象

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引用次数: 0

Vanillic Acid-Loaded Niosomes for Diabetic Wound Healing: Formulation, Optimization by Box–Behnken Design, and In Vivo Evaluation 用于糖尿病伤口愈合的香草酸负载Niosomes：配方、Box-Behnken设计优化和体内评估

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03249-7

Shervin Amirkhanloo, Reza Enayatifard, Jafar Akbari, Mohammad Seyedabadi, Majid Saeedi, Mohammad Ranaee

In this study, a niosomal formulation of vanillic acid was successfully developed to enhance its poor aqueous solubility and antioxidant therapeutic potential. Niosomes were prepared using Span 60 and cholesterol via thin-film hydration method followed by probe sonication and were optimized using a Box–Behnken design. The optimized formulation exhibited a vesicle size of 129.91 ± 2.78 nm, a polydispersity index (PDI) of 0.152 ± 0.06, a zeta potential of − 8.698 ± 0.52 mV, and an entrapment efficiency (EE%) of 35.893 ± 3.45%. Physicochemical analyses confirmed spherical morphology and amorphous drug dispersion. In vitro drug release showed a sustained profile governed by the Korsmeyer–Peppas model, indicating diffusion-controlled release as the main mechanism. Antioxidant assays, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), revealed significantly elevated enzymatic activity in the nanoformulation-treated groups. In vivo evaluation using a diabetic Wistar rat model showed that the 1% Niosome–Vanillic Acid containing formulation led to superior wound closure, increased hydroxyproline content, and improved histopathological features. These findings highlighted nano-encapsulated vanillic acid as a promising therapeutic strategy for diabetic wound healing.

Graphical Abstract

在这项研究中，成功开发了香草酸的niosomal配方，以改善其差的水溶性和抗氧化治疗潜力。以Span 60和胆固醇为原料，采用薄膜水化法制备了脂质体，并采用Box-Behnken设计对脂质体进行了优化。优化后的微泡尺寸为129.91±2.78 nm，多分散指数（PDI）为0.152±0.06，zeta电位为−8.698±0.52 mV，包封效率（EE%）为35.893±3.45%。理化分析证实其呈球形和非晶态分散。体外释放受Korsmeyer-Peppas模型控制，表明扩散控制释放是主要机制。抗氧化测试，包括超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx），显示纳米配方处理组的酶活性显著升高。使用糖尿病Wistar大鼠模型进行的体内评估显示，含有1% nio质体香草酸的配方可以更好地关闭伤口，增加羟脯氨酸含量，改善组织病理学特征。这些发现强调了纳米封装香草酸作为糖尿病伤口愈合的一种有前途的治疗策略。图形抽象

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引用次数: 0

Effect of Process and Formulation Variables on Quality, Stability, and Taste of Lamivudine Printlets Manufactured by Binder Jetting 3D Printing Method 工艺和配方对粘合剂喷射3D打印拉米夫定小片质量、稳定性和口感的影响

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03289-z

Tahir Khuroo, Linh H. Maracchini, Ziyaur Rahman, Mansoor A. Khan

This study investigated effect of formulation and process variables on the quality attributes of lamivudine printlets manufactured by binder jetting 3D printing method. The variables studied through fractional design of experiment were number of solvent sprays, delay time, powder layer thickness, drying temperature and hydroxypropyl methyl percentage. The printlets were assessed for hardness, disintegration time (DT), and dissolution and chemical information by X-ray powder diffraction (XRPD) and Fourier transformed spectroscopy, near infrared hyperspectroscopy, and taste evaluation by electronic tongue. The printlet hardness and DT ranged from 2.5 to 21.1 N, and 2.3 to 317 s, respectively. The dissolution profile met USP specifications of > 85% drug dissolved in 30 min. XRPD indicated partial amorphization of the drug in the printlets and hyperspectroscopy indicated uniform distribution of the components in the formulation. Stability data indicated no significant change in quality of the printlets in terms of dissolution and assay. Excipients used in the formulation reduced the bitterness of the drug to some degree. In summary, binder jetting can be used to print personalized medication with quality control characteristics.

Graphical Abstract

本研究考察了配方和工艺变量对粘合剂喷射3D打印法制备拉米夫定小片质量属性的影响。通过分级设计的实验，研究了溶剂喷雾次数、延迟时间、粉层厚度、干燥温度和羟丙基甲基含量。采用x射线粉末衍射（XRPD）、傅立叶变换光谱、近红外超光谱和电子舌法测定样品的硬度、崩解时间、溶出度和化学信息。试样硬度和DT范围分别为2.5 ~ 21.1 N和2.3 ~ 317 s。溶出度符合USP标准：30 min溶出85%。XRPD显示药物在小片中部分非晶化，高光谱显示制剂中成分分布均匀。稳定性数据表明，在溶出度和测定方面，样品的质量没有显著变化。配方中使用的辅料在一定程度上减轻了药物的苦味。综上所述，活页胶喷射可用于打印具有质量控制特性的个性化药物。图形抽象

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引用次数: 0

Development of Diclofenac Acid Encapsulated Transferosomal gel with Enhanced Antioxidant and Anti-Inflammatory Activities for the Management of Musculoskeletal Pain 具有增强抗氧化和抗炎活性的双氯芬酸胶囊转移体凝胶的开发用于肌肉骨骼疼痛的治疗

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03276-4

Subhrasima Nayak, Arka Karmakar, Sampada Shinde, Lalit Kumar

Myopathies, joint impairment, muscle spasm, and torn muscles cause an excessive amount of musculoskeletal inflammation, which ultimately causes muscular soreness and stiffness, leading to difficulty in mobility. NSAIDs can suppress the COX enzyme, crucial for converting arachidonic acid into prostaglandin-E₂. Oxidative burden increases during impaired health conditions, alleviating and prolonging the inflammatory phase and pain sensation. DA is a widely accepted NSAID that functions as a non-specific inhibitor of COX and is reported to have antioxidant properties. However, it has low solubility and severe adverse effects when used at high doses over a long-term therapy. Thus, the objective of this study is to develop a DA-loaded transferosomal gel with promising anti-inflammatory and antioxidant activity that resembles the commercially available gel, with improved solubility, decreasing the higher dose regimen, minimize potential side effects, and facilitating muscular pain relief over a long period of time. Transferosomes were prepared with a modified thin film hydration technique. The optimized formulation attained the desired particle size, PDI, and zeta potential with high entrapment. The transferosomal gel was investigated for physical characterization, in vitro diffusion, ex vivo permeation, and cellular studies. A cumulative drug release of 92.89 ± 4.21% was achieved after 10 h. The transferosomal gel demonstrated exceptional regulated drug diffusion of 90.68 ± 1.42% over 24 h and permeation of 99.57 ± 6.41% over 48 h. This formulation also exhibited better antioxidant and anti-inflammatory activities than the marketed gel after investigation of in vitro cellular studies. Based on acquired results, it is concluded that DA-loaded transferosomal gel may be potentially effective for reducing musculoskeletal inflammation and providing pain relief.

Graphical Abstract

肌病、关节损伤、肌肉痉挛和肌肉撕裂会引起过多的肌肉骨骼炎症，最终导致肌肉酸痛和僵硬，导致行动困难。非甾体抗炎药可以抑制COX酶，而COX酶是花生四烯酸转化为前列腺素e2的关键。在健康受损的情况下，氧化负担增加，减轻和延长炎症期和疼痛感觉。DA是一种被广泛接受的非甾体抗炎药，作为COX的非特异性抑制剂，据报道具有抗氧化特性。然而，它具有低溶解度和严重的不良反应，当使用在高剂量长期治疗。因此，本研究的目的是开发一种具有抗炎和抗氧化活性的da负载转移体凝胶，与市售凝胶相似，具有更好的溶解度，减少高剂量方案，最大限度地减少潜在的副作用，并促进长期肌肉疼痛缓解。采用改进的薄膜水合技术制备了转移体。优化后的配方获得了理想的粒径、PDI和zeta电位，并具有较高的包裹度。研究了转移体凝胶的物理特性、体外扩散、体外渗透和细胞研究。10 h后的累积释药率为92.89±4.21%，24 h内的药物扩散率为90.68±1.42%，48 h内的药物渗透率为99.57±6.41%。体外细胞研究表明，该制剂比市售凝胶具有更好的抗氧化和抗炎活性。基于已获得的结果，我们得出结论，负载da的转移体凝胶可能对减少肌肉骨骼炎症和缓解疼痛有潜在的有效作用。图形抽象

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