AAPS PharmSciTech最新文献_第3页

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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引用次数: 0

Smart Stings of Nature: Harnessing Microneedles Assisted Targeted Phytoconstituent Delivery for Dermatological Disorders 自然的智能刺：利用微针辅助靶向植物成分递送皮肤疾病

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03311-4

Akshay Kumar, Suresh Babu Kondaveeti, Arpan Kumar Tripathi, Mohit Agrawal, Thakur Gurjeet Singh, Devesh Kumar, Mohit Kumar

Microneedle-mediated transdermal delivery of phytoconstituents represents a sophisticated and emerging paradigm in dermatological therapeutics, bridging the pharmacological efficacy of plant-derived bioactive with the precision of advanced biomedical engineering. Conventional topical dosage forms are often constrained by the formidable barrier function of the stratum corneum, instability of phytochemicals, and suboptimal patient adherence. Microneedle arrays circumvent these limitations by creating transient microchannels that enable minimally invasive, painless, and controlled delivery of therapeutics into the viable epidermal and dermal layers. The bioactive compounds such as curcumin, resveratrol, asiaticoside, and glycyrrhizin exhibit multifaceted pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and pro-regenerative effects, which are beneficial for the management of cutaneous pathologies such as psoriasis, eczema, acne vulgaris, and chronic ulcerations. The incorporation of these phytoconstituents into dissolving or hydrogel-forming microneedles enhances their physicochemical stability, facilitates sustained and localized drug release, and minimizes systemic exposure, thereby improving therapeutic efficacy and safety. The utilization of natural, biodegradable, and biocompatible polymers such as chitosan, hyaluronic acid, silk fibroin, and alginate, further augments the structural integrity and bioperformance of microneedle systems while aligning with eco-sustainable pharmaceutical design principles. This integrative strategy signifies a pivotal advancement toward personalized dermatological interventions, enabling precise dosing and targeted pharmacokinetics. The future research should emphasize material innovation, in vivo pharmacodynamic assessment, and large-scale translational studies to validate the clinical potential of phytoconstituent-loaded microneedles as next-generation bioresponsive platforms for skin therapeutics.

Graphical Abstract

微针介导的植物成分透皮给药代表了皮肤科治疗中一种复杂和新兴的范例，将植物源性生物活性的药理功效与先进生物医学工程的精确性联系起来。传统的外用剂型常常受到角质层强大的屏障功能、植物化学物质的不稳定性以及患者依从性欠佳的限制。微针阵列通过创建瞬时微通道来规避这些限制，从而实现微创、无痛和可控地将治疗药物输送到可存活的表皮和真皮层。姜黄素、白藜芦醇、积雪草苷和甘草酸等生物活性化合物具有多方面的药理活性，包括抗炎、抗氧化、抗菌和促再生作用，对牛皮癣、湿疹、寻常痤疮和慢性溃疡等皮肤疾病的治疗有益。将这些植物成分掺入溶解性或水凝胶形成的微针中可以增强其物理化学稳定性，促进持续和局部药物释放，并最大限度地减少全身暴露，从而提高治疗疗效和安全性。利用天然、可生物降解和生物相容性聚合物，如壳聚糖、透明质酸、丝素蛋白和海藻酸盐，进一步增强了微针系统的结构完整性和生物性能，同时符合生态可持续的药物设计原则。这种综合策略标志着个性化皮肤病学干预的关键进步，使精确的剂量和靶向药代动力学成为可能。未来的研究应强调材料创新、体内药效学评估和大规模转化研究，以验证植物成分负载微针作为下一代皮肤治疗生物反应平台的临床潜力。图形抽象

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引用次数: 0

Amphotericin B-Loaded Bigel: Characterization and in vivo Antileishmanial Evaluation in BALB/c Mice Infected with Leishmania amazonensis 两性霉素b负载Bigel: BALB/c小鼠感染亚马逊利什曼原虫的特性和体内抗利什曼原虫的评价

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03303-4

Rosilene Ribeiro de Sousa, Matheus Oliveira do Nascimento, Leandro Josuel da Costa Santos, Francisco Gesley de Sousa Abreu, André Luiz Pinheiro de Moura, Daniele Costa Lopes, Karla Germana dos Reis Bacelar, Rita de Cássia Vianna de Carvalho, Paulline Paiva Mendes de Souza Leal, Charllyton Luis Sena da Costa, Vitória de Cássia Coelho Rodrigues, Fernando Aécio de Amorim Carvalho, Michel Muálem de Moraes Alves, André Luis Menezes Carvalho

American Tegumentary Leishmaniasis (ATL) is a zoonotic disease characterized by polymorphic cutaneous and mucosal manifestations, caused by protozoa of the genus Leishmania and transmitted through the bite of sandflies. Current treatment relies on pharmacotherapy with drugs such as amphotericin B (AmB), which is limited by adverse effects. Novel topical formulations of AmB, including bigels, have been investigated as alternatives for ATL therapy, aiming to achieve local efficacy with reduced toxicity and lower cost. This study sought to develop and characterize an AmB loaded-bigel for topical application and to evaluate its in vivo antileishmanial activity. The formulations were characterized by organoleptic analysis, pH, stability, oil retention capacity, swelling, spreadability, and texture profile. In vitro drug release and skin permeation were assessed using Franz diffusion cells and murine skin, while the ocular irritation potential was evaluated through the HET-CAM assay. In vivo efficacy was tested in BALB/c mice infected with Leishmania amazonensis, monitoring lesion progression and parasite burden. Treatment with the AmB loaded-bigel resulted in a 74.1% reduction in parasite load. Overall, the bigel demonstrated favorable physicochemical properties, stability, spreadability, and controlled release of AmB. The in vivo findings highlight its promising antileishmanial activity and support the potential of AmB-loaded bigels as a therapeutic alternative for ATL.

Graphical Abstract

美洲背囊利什曼病（ATL）是一种人畜共患疾病，其特征是皮肤和粘膜表现多形性，由利什曼属原生动物引起，通过白蛉叮咬传播。目前的治疗依赖于药物治疗，如两性霉素B (AmB)，其副作用有限。包括bigels在内的新型AmB外用制剂已被研究作为ATL治疗的替代方案，旨在以更低的毒性和更低的成本实现局部疗效。本研究旨在开发和表征一种局部应用的AmB负载bigel，并评估其体内抗利什曼原虫活性。通过感官分析、pH值、稳定性、保油能力、溶胀性、涂抹性和质地特征对配方进行了表征。采用Franz扩散细胞法和小鼠皮肤法评估体外药物释放和皮肤渗透，并通过ht - cam法评估眼部刺激电位。在感染亚马逊利什曼原虫的BALB/c小鼠中检测其体内疗效，监测病变进展和寄生虫负荷。用AmB -bigel处理可使寄生虫载量降低74.1%。总体而言，该凝胶具有良好的理化性质、稳定性、展布性和AmB的控释性。在体内的研究结果突出了其有希望的抗利什曼活性，并支持了amb负载bigels作为ATL治疗替代方案的潜力。图形抽象

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引用次数: 0

Development, Stability, and Clinical Efficacy of an Oil-in-Serum Formulation with Olive Extract Standardized in Hydroxytyrosol for Post-Inflammatory Hyperpigmentation Treatment 羟酪醇标准橄榄提取物血清油配方用于炎症后色素沉着治疗的开发、稳定性和临床疗效

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03318-x

B. J. Navarro, L. Kakuda, P. M. B. G. Maia Campos

Post-inflammatory hyperpigmentation (PIH) is a prevalent dermatological condition arising from inflammatory processes that significantly impacts quality of life. Natural alternatives to conventional treatments are increasingly sought to minimize adverse effects while maintaining efficacy. This study aimed to develop and evaluate an innovative oil-in-serum formulation containing olive extract standardized in hydroxytyrosol (HT) for PIH treatment, assessing its stability, sensory properties, and clinical efficacy. Two complementary formulations were developed: a hydroxyethylcellulose-based gel (with/without 0.1% olive extract containing 20% HT) and an olive oil-based formulation. Stability tests, texture analysis, sensory evaluation and clinical efficacy analysis in participants with PIH were conducted. Overall, the formulations were stable and showed favorable sensory properties. The oil-in-serum system exhibited enhanced spreadability, hydration perception, and reduced stickiness compared to individual components. After 45 days of application, the formulation with HT increased stratum corneum water content and reduced transepidermal water loss (TEWL), indicating improved skin barrier function. A significant reduction in color difference between lesional and perilesional areas was observed in high-resolution imaging analysis, showing a reduction in the PIH. Participants reported enhanced skin hydration and reduced dark spots, which corroborate the instrumental measurements results. Finally, the oil-in-serum formulation with olive extract standardized in HT proved effective for PIH treatment, combining excellent sensory properties with clinical efficacy in improving skin hydration, barrier function, and hyperpigmentation control.

Graphical Abstract

炎症后色素沉着（PIH）是一种常见的皮肤病，由炎症过程引起，严重影响生活质量。人们越来越多地寻求传统疗法的天然替代品，以尽量减少副作用，同时保持疗效。本研究旨在开发和评估一种创新的血清油配方，该配方含有标准化的橄榄提取物羟酪醇（HT），用于治疗PIH，评估其稳定性、感官特性和临床疗效。开发了两种互补配方：基于羟乙基纤维素的凝胶（含/不含含20% HT的0.1%橄榄提取物）和基于橄榄油的配方。对PIH患者进行稳定性试验、质地分析、感觉评价和临床疗效分析。总体而言，该配方稳定且具有良好的感官性能。与单个成分相比，血清油系统表现出增强的涂抹性、水合感和降低的粘性。使用45天后，含HT的配方增加了角质层含水量，减少了经皮失水（TEWL），表明皮肤屏障功能得到改善。在高分辨率成像分析中观察到病变区域和病变周围区域之间的色差显著减少，显示PIH减少。参与者报告皮肤水合作用增强，黑斑减少，这证实了仪器测量结果。最后，在HT中标准化的橄榄提取物血清油配方被证明是有效的PIH治疗，结合了优异的感官特性和改善皮肤水合，屏障功能和控制色素沉着的临床疗效。图形抽象

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引用次数: 0