Journal of Drug Delivery Science and Technology最新文献_第7页

Development and pharmacokinetic evaluation of novasomes using crodamol oil-carboxymethyl chitosan conjugate for the transnasal delivery of Remdesivir crodamol油-羧甲基壳聚糖缀合物用于瑞德西韦经鼻给药的novasome的研制及药代动力学评价

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-15 DOI: 10.1016/j.jddst.2025.107928

Muhammad Ibrahim, Muhammad Irfan, Ghulam Abbas

Remdesivir (RDV) is thought to be more effective antiviral than other medications for the treatment of coronavirus and associated respiratory infections. It is classified as BCS class II, has a low water solubility, and has a poor oral bioavailability. In order to overcome these obstacles, this study concentrated on transnasal administration, which can avoid hepatic first-pass metabolism and allow for quicker absorption because of the copious blood supply around nasal cavity and microvilli. The goal of this investigation was the preparation and characterization of CO-CMCS-based novasomes for effective nasal delivery of RDV. The CO-CMCS conjugate made up by enduring chemical alteration of the crodamol oil (CO) to integrate carboxylic acid in medium-chain triglyceride oil for novasome formulation. Novasomes were further optimized using software Design Expert version 13, Stat-Ease Inc. USA. A central composite design has been used to examine how crodamol oil (CO) and carboxymethyl chitosan (CMCS) affect the concentration of CO-CMCS conjugates and their characteristics in novasomes. % RDV release, % permeation, and mucoadhesion were picked as the key evaluators. Structural confirmation was performed using FTIR and TLC. The novasome adherence time for the RSCN9 formulation was 11.8 h, with RDV release and penetration rates of 90 % and 98 %, respectively. Compared to the pure RDV suspension given orally, the transnasal administration of the RSCN9 formulation resulted in a 1.9-fold increase in RDV bioavailability and antiviral activity. The entrapment efficiency, zeta potential, and particle size of the generated novasomes were assessed. With a zeta potential of −4.25 mV, a particle size of 82–108 nm, and PDI values below 0.3, the improved formulation (RSCN9) demonstrated a stable and homogeneous nanosized vesicle system. RSCN9 had the highest drug entrapment efficiency (80.8 %). Therefore, nasally delivered RDV-loaded novasomes may represent a breakthrough in the treatment of respiratory viral infections, especially coronavirus. The DSC and TGA studies of the RSCN9 formulation demonstrated that the drug had been dispersed amorphously and uniformly throughout the novasomes.

瑞德西韦（Remdesivir， RDV）被认为比其他治疗冠状病毒和相关呼吸道感染的药物更有效。它被归类为BCS II类，水溶性低，口服生物利用度差。为了克服这些障碍，本研究将重点放在经鼻给药上。经鼻给药可以避免肝脏首过代谢，并且由于鼻腔和微绒毛周围有丰富的血液供应，可以使吸收更快。本研究的目的是制备和表征基于co - cmc的新体，用于有效的鼻腔给药RDV。该CO- cmcs偶联物是通过对crodamol油（CO）进行化学改变，将羧酸整合到中链甘油三酯油中，用于新酶体制剂。使用Stat-Ease Inc.的Design Expert version 13软件对novasome进行了进一步优化。美国。采用中心复合设计研究了crodamol oil （CO）和carboxy甲基壳聚糖（CMCS）如何影响CO-CMCS偶联物的浓度及其在novassomes中的特性。以RDV释放率、渗透率和黏附率为主要评价指标。用FTIR和TLC进行结构确认。RSCN9配方的novasome粘附时间为11.8 h， RDV释放率和穿透率分别为90%和98%。与口服纯RDV混悬液相比，经鼻给药RSCN9制剂可使RDV的生物利用度和抗病毒活性增加1.9倍。对生成的新体的包封效率、zeta电位和粒径进行了评估。改进配方（RSCN9）的zeta电位为- 4.25 mV，粒径为82 ~ 108 nm， PDI值小于0.3，表现出稳定均匀的纳米囊泡体系。RSCN9包封率最高（80.8%）。因此，鼻腔递送装载rdv的新泌体可能代表着呼吸道病毒感染，特别是冠状病毒治疗的突破。RSCN9制剂的DSC和TGA研究表明，该药物在整个novas小体中呈无定形均匀分布。

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引用次数: 0

Intranasal dabigatran etexilate lipid nanoparticles: A targeted approach for management of Alzheimer's disease 鼻内达比加群酯脂质纳米颗粒：治疗阿尔茨海默病的靶向方法

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-14 DOI: 10.1016/j.jddst.2025.107925

Nadine K. Baher , Lamia A. Heikal , Noha S. El-Salamouni , Passent M.E. Gaafar , Basant A. Bakr , Noha M. Badae , Safaa S. ElGamal

Cognitive decline is a hallmark of Alzheimer's disease (AD), a progressive neurological condition. In this work, dabigatran etexilate (DE) was, for the first time, incorporated into chitosan-coated lipid nanoparticles (CS-DE-NPs) designed for non-invasive intranasal delivery to manage cognitive dysfunction. The nanoplatform was developed using both solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), with fish oil incorporated as the liquid lipid to enhance functionality. The formulations were thoroughly evaluated through in-vitro characterization and in-vivo evaluation in a sporadic Alzheimer's disease (SAD) rat model induced by intracerebroventricular administration of streptozotocin (5 mg/kg, ICV-STZ). Both prophylactic and therapeutic regimens of DE suspension and CS-DE-NPs (5 mg/kg) were investigated, administered either 3 days before or 5 h after ICV-STZ, followed by 22 days of daily dosing. The optimized chitosan-coated nanoplatform demonstrated advantageous properties, including nanometric particle size (∼190 nm) with enhanced entrapment efficiency (>98 %), and positive surface charge (∼+21 mV). Intranasal CS-DE-NPs significantly improved short- and long-term spatial memory, reduced amyloid plaque burden, preserved neuronal survival, and exerted strong antioxidant effects. Biochemical assays further revealed a 3-fold reduction in β-amyloid (Aβ) aggregation and a 4-fold suppression of hyperphosphorylated tau, with no signs of nasal irritation, confirming safety and tolerability. Overall, this study introduces a novel dual-functional nanoplatform that integrates pharmaceutical and natural components for brain delivery, providing superior efficacy over DE suspension in attenuating AD pathology and improving cognition in SAD rats. Importantly, the system showed greater prophylactic than therapeutic benefit, highlighting its potential as a first-in-class translational nose-to-brain strategy for AD management.

认知能力下降是阿尔茨海默病（AD）的标志，这是一种进行性神经系统疾病。在这项工作中，达比加群酯（DE）首次被纳入壳聚糖包被脂质纳米颗粒（CS-DE-NPs），设计用于无创鼻内给药以治疗认知功能障碍。该纳米平台采用固体脂质纳米颗粒（sln）和纳米结构脂质载体（NLCs）开发，并加入鱼油作为液体脂质以增强功能。在脑室内给药链脲佐菌素（5 mg/kg, ICV-STZ）诱导的散发性阿尔茨海默病（SAD）大鼠模型中，通过体外表征和体内评价对配方进行了全面评估。研究了DE悬浮液和CS-DE-NPs （5mg /kg）的预防和治疗方案，分别在ICV-STZ前3天或后5小时给药，随后每天给药22天。优化后的壳聚糖包覆纳米平台具有优异的性能，包括纳米粒径（~ 190 nm），包覆效率提高（> 98%），表面带正电荷（~ +21 mV）。经鼻注射的CS-DE-NPs可显著改善短期和长期空间记忆，减少淀粉样斑块负担，保存神经元存活，并具有较强的抗氧化作用。生化分析进一步显示β-淀粉样蛋白（a β）聚集减少3倍，过度磷酸化的tau蛋白抑制4倍，无鼻刺激迹象，证实了安全性和耐受性。总的来说，本研究引入了一种新的双功能纳米平台，该平台整合了药物和天然成分用于脑递送，在减轻AD病理和改善SAD大鼠认知方面具有比DE悬浮液更优越的功效。重要的是，该系统显示出比治疗更大的预防效益，突出了其作为AD管理的一流转化鼻到脑策略的潜力。

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引用次数: 0

Targeting diabetic wounds with nanostructured lipid carriers: A pathogenesis-guided, drug-repurposing approach 用纳米结构脂质载体靶向糖尿病伤口：一种病因导向、药物再利用的方法

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-13 DOI: 10.1016/j.jddst.2025.107923

Abhishek Chauhan , Vaishali Thakur , Sonia Dhiman , Thakur Gurjeet Singh , Mohit Kumar , Syed Mahmood , Bharat Kumar Reddy Sanapalli , Ankit Awasthi

Diabetic wounds are a major complication of diabetes mellitus, characterized by delayed healing, chronic inflammation, impaired angiogenesis, and microbial colonization. Conventional therapies often fail to address the multifactorial pathogenesis and suffer from poor drug retention, limited penetration, and systemic side effects. Topical drug delivery offers a localized, non-invasive approach to wound management, but its success hinges on overcoming the skin barrier and ensuring sustained therapeutic action. Nanostructured lipid carriers (NLCs), composed of solid and liquid lipid blends, have emerged as a promising platform for topical delivery due to their enhanced skin permeation, occlusive properties, and controlled drug release. This review highlights the potential of NLCs in delivering therapeutics directly to diabetic wound sites, aligning drug release profiles with the wound's pathological timeline. Special emphasis is placed on the repurposing of Biopharmaceutics Classification System (BCS) Class IV drugs—agents with poor solubility and permeability but promising pharmacological activity in modulating oxidative stress, inflammation, and angiogenesis. By encapsulating these drugs in NLCs, their permeability and therapeutic index can be significantly improved for topical application. We discuss formulation strategies, release mechanisms, and physicochemical considerations for NLC-based topical systems, supported by literature on preclinical and clinical studies. Additionally, the review explores translational challenges, proposing future directions.

糖尿病伤口是糖尿病的主要并发症，其特点是愈合延迟、慢性炎症、血管生成受损和微生物定植。传统的治疗方法往往不能解决多因素的发病机制，并且存在药物潴留不良、渗透有限和全身副作用。局部给药为伤口管理提供了一种局部的、非侵入性的方法，但其成功取决于克服皮肤屏障并确保持续的治疗作用。纳米结构脂质载体（nlc）由固体和液体脂质混合物组成，由于其增强的皮肤渗透性、闭塞性和药物释放控制，已成为一种有前途的局部给药平台。这篇综述强调了NLCs在将治疗药物直接输送到糖尿病伤口部位方面的潜力，使药物释放曲线与伤口的病理时间线一致。特别强调的是生物制药分类系统（BCS） IV类药物的重新用途-溶解度和渗透性较差但在调节氧化应激，炎症和血管生成方面有前景的药理活性的药物。通过将这些药物包埋在NLCs中，它们的通透性和治疗指数可以显着提高，用于局部应用。在临床前和临床研究文献的支持下，我们讨论了基于nlc的局部系统的配方策略、释放机制和物理化学考虑。此外，本文还探讨了翻译面临的挑战，并提出了未来的发展方向。

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引用次数: 0

Preparation and evaluation of human serum albumin-based nanoparticles for combined photothermal and chemotherapy in colorectal cancer treatment 光热联合化疗治疗结直肠癌的人血清白蛋白纳米颗粒制备及评价

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-13 DOI: 10.1016/j.jddst.2025.107922

Doudou He , Junli Cui , Jialin Yao , Ying Xu , Kaikai Wang

Colorectal cancer (CRC) remains a major global health challenge, with limited efficacy of conventional chemotherapy due to drug resistance and toxicity. This study introduces human serum albumin (HSA)-based nanoparticles co-loaded with paclitaxel (PTX) and IR780 for synergistic chemotherapy and photothermal therapy (PTT). Nanoparticles were prepared via a dithiothreitol (DTT)-mediated “molecular switch” self-assembly method, optimizing drug addition sequences (Formulation1, F1: IR780 first, then PTX; Formulation2, F2: simultaneous; Formulation3, F3: PTX first, then IR780) to achieve high drug loading and encapsulation efficiencies. Physicochemical characterization revealed spherical particles (∼146 nm for F1). In vitro, F1 exhibited pH- and laser-responsive PTX release (up to 51.26 % under laser), 3.7-fold enhanced cellular uptake in CT-26 cells compared to free IR780, and synergistic cytotoxicity (cell viability <35 % at high doses with laser). In vivo pharmacokinetics in mice showed prolonged half-life (18.56 h for F1 vs. 11.37 h for free IR780), while NIR imaging confirmed superior tumor accumulation via the EPR effect and reduced off-target distribution. Antitumor efficacy in CT-26 tumor-bearing mice demonstrated near-complete tumor suppression with F1 plus laser, outperforming single-modality treatments. These findings highlight the potential of sequence-optimized HSA nanoparticles as a biocompatible platform for multimodal CRC therapy, warranting further clinical exploration.

结直肠癌（CRC）仍然是一个主要的全球健康挑战，由于耐药和毒性，传统化疗的疗效有限。本研究介绍了以人血清白蛋白（HSA）为基础的纳米粒子与紫杉醇（PTX）和IR780共载，用于协同化疗和光热治疗（PTT）。采用二硫苏糖醇（DTT）介导的“分子开关”自组装法制备纳米颗粒，优化药物加成顺序（Formulation1, F1: IR780，然后是PTX； Formulation2， F2：同时；Formulation3, F3: PTX，然后是IR780），以获得较高的载药和包封效率。物理化学表征显示球形颗粒（F1为~ 146 nm）。在体外，F1表现出pH和激光响应的PTX释放（激光下高达51.26%），与游离的IR780相比，CT-26细胞的细胞摄取增加3.7倍，并且具有协同细胞毒性（高剂量激光下细胞存活率& 35%）。小鼠体内药代动力学显示，F1的半衰期延长（18.56 h，而游离IR780的半衰期为11.37 h），而近红外成像通过EPR效应证实了较好的肿瘤积累，并减少了脱靶分布。在CT-26荷瘤小鼠中，F1 +激光的抗肿瘤效果几乎完全抑制肿瘤，优于单模态治疗。这些发现强调了序列优化的HSA纳米颗粒作为多模式结直肠癌治疗的生物相容性平台的潜力，值得进一步的临床探索。

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引用次数: 0

Simple and stable (−)-α-Bisabolol-encapsulated nanoemulsion for enhanced topical delivery in atopic dermatitis treatment 简单稳定的(−)-α-双abolol包封纳米乳用于治疗特应性皮炎

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-12 DOI: 10.1016/j.jddst.2025.107920

Yu Lin , Han Liang , Yongtao Yan , Mingkun Li , Xiaomin Li , Xiang Liu , Yan-Long Ma

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by immune dysregulation and skin barrier dysfunction. Current treatments often have adverse effects, necessitating safer alternatives. (−)-α-Bisabolol (BIS), a natural sesquiterpene alcohol, exhibits anti-inflammatory properties but faces limitations in topical delivery due to poor solubility and limited skin permeability. To address these issues, we developed a BIS-loaded oil-in-water nanoemulsion (BIS_O/W_NE) using nanoemulsion technology, optimized with isooctyl palmitate, caprylic/capric triglyceride, Tween 80, and propylene glycol. The optimized BIS_O/W_NE exhibited a particle size of 139.9 ± 1 nm and zeta potential of −58.1 ± 1.2 mV, with 84 % encapsulation efficiency and stability over 12 months. In vitro release studies showed pH-dependent release, optimal at pH 6, aligning with AD skin pH. Skin permeation experiments revealed a 1.75-fold higher flux for BIS_O/W_NE compared to free BIS. In vitro, BIS_O/W_NE suppressed mast cell degranulation and cytokine release (IL-4, IL-13) in RBL-2H3 cells and inhibited LPS-induced macrophage activation in Raw264.7 cells. In a DNCB-induced AD mouse model, BIS_O/W_NE (38.3 mM BIS, topical administration) alleviated symptoms, reducing epidermal thickening and mast cell infiltration, outperforming free BIS. This study highlights BIS_O/W_NE as a topical drug delivery system for AD, overcoming BIS's limitations with enhanced solubility, pH-responsive release, and improved skin permeation and pharmacological effect. The optimized formulation shows therapeutic potential by targeting mast cells and macrophages, offering an effective alternative to current therapies.

特应性皮炎（AD）是一种以免疫失调和皮肤屏障功能障碍为特征的常见炎症性皮肤病。目前的治疗方法往往有副作用，需要更安全的替代方法。（−）-α-双abolol （BIS）是一种天然倍半萜醇，具有抗炎特性，但由于溶解度差和皮肤渗透性有限，局部给药受到限制。为了解决这些问题，我们利用纳米乳液技术开发了一种负载bis的水包油纳米乳液（BIS_O/W_NE），并以棕榈酸异辛酯、癸酸/癸酸甘油三酯、Tween 80和丙二醇为优化剂。优化后的BIS_O/W_NE的粒径为139.9±1 nm， zeta电位为- 58.1±1.2 mV，封装效率为84%，封装稳定性为12个月。体外释放研究显示，pH依赖性释放，在pH 6时达到最佳，与AD皮肤pH一致。皮肤渗透实验显示，BIS_O/W_NE的通量比游离BIS高1.75倍。在体外，BIS_O/W_NE抑制RBL-2H3细胞肥大细胞脱颗粒和细胞因子（IL-4、IL-13）释放，抑制lps诱导的Raw264.7细胞巨噬细胞活化。在dncb诱导的AD小鼠模型中，BIS_O/W_NE （38.3 mM BIS，外用）减轻了症状，减少了表皮增厚和肥大细胞浸润，优于游离BIS。本研究强调BIS_O/W_NE作为AD的局部给药系统，克服了BIS的局限性，增强了溶解度，ph响应性释放，改善了皮肤渗透和药理作用。优化后的配方通过靶向肥大细胞和巨噬细胞显示出治疗潜力，为目前的治疗提供了有效的替代方案。

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引用次数: 0

Multifunctional calcium alginate hydrogels with resveratrol-loaded nanoparticles and adipose derived stem cells for wound healing and photoaging therapy 含有白藜芦醇纳米颗粒和脂肪干细胞的多功能海藻酸钙水凝胶用于伤口愈合和光老化治疗

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-11 DOI: 10.1016/j.jddst.2025.107919

Shiqi Ye , Chunyu Kang , Peng Du

Background

Chronic wounds and skin aging share common pathological mechanisms, including oxidative stress, inflammation, and extracellular matrix (ECM) degradation. Advanced biomaterials capable of addressing these processes simultaneously hold promise for improving healing outcomes.

Methods

Calcium alginate (CALALG)-based nanocomposite hydrogels were fabricated and tested in a rat model of excisional wound healing and photoaging. Hydrogel formulations included CALALG, CALALG with chitosan nanoparticles (CALALG-CNP), CALALG with resveratrol-loaded chitosan nanoparticles (CALALG Resv-CNPs-4), CALALG with adipose-derived stem cells (ASCs) (CALALGASCs), and CALALG with both resveratrol-loaded nanoparticles and ASCs (CALALG-Resv-ASCs). Wound closure, histology, and biochemical assays for growth factors, cytokines, and antioxidant markers were performed to assess regenerative, anti-inflammatory, and anti-aging efficacy.

Results

CALALG-Resv-ASCs demonstrated superior wound closure and collagen deposition compared to control and other hydrogel groups. ELISA revealed significantly increased vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), transforming growth factor beta 1 (TGF-β1), platelet-derived growth factor subunit BB (PDGF-BB), tissue inhibitor of metalloproteinases-1 (TIMP-1), collagen type I alpha 1 (COL1A1), and collagen type III alpha 1 (COL3A1), alongside reduced tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-1 (MMP-1), and matrix metalloproteinase-3 (MMP-3). Antioxidant defense marker superoxide dismutase (SOD) was elevated.

Conclusion

This study demonstrated that CALALG-Resv-ASCs hydrogels enhanced wound repair and exhibited anti-aging potential in vivo. The combination of ASCs and resveratrol within a calcium alginate-based system provides a promising foundation for developing multifunctional biomaterials aimed at improving skin regeneration and preventing tissue degeneration.

慢性伤口和皮肤老化具有共同的病理机制，包括氧化应激、炎症和细胞外基质（ECM）降解。能够同时解决这些过程的先进生物材料有望改善愈合效果。方法制备海藻酸钙（CALALG）纳米复合水凝胶，并在大鼠切除创面愈合和光老化模型上进行实验。水凝胶配方包括CALALG、CALALG含壳聚糖纳米颗粒（CALALG- cnp）、CALALG含白藜芦醇壳聚糖纳米颗粒（CALALG Resv-CNPs-4）、CALALG含脂肪源性干细胞（CALALGASCs）、CALALG含白藜芦醇纳米颗粒和ASCs （CALALG- resv -ASCs）。进行伤口闭合、组织学和生长因子、细胞因子和抗氧化标志物的生化分析，以评估再生、抗炎和抗衰老的功效。结果与对照组和其他水凝胶组相比，scalal - resv - ascs表现出更好的伤口闭合和胶原沉积。ELISA结果显示，血管内皮生长因子A （VEGF-A）、成纤维细胞生长因子2 （FGF-2）、转化生长因子β1 （TGF-β1）、血小板衍生生长因子亚基BB （PDGF-BB）、金属蛋白酶组织抑制剂-1 （TIMP-1）、I型α 1 （COL1A1）、III型α 1 （COL3A1）显著升高，肿瘤坏死因子α (TNF-α)、白细胞介素6 （IL-6）、基质金属蛋白酶1 （MMP-1）、基质金属蛋白酶3 （MMP-3）显著降低。抗氧化防御标志物超氧化物歧化酶（SOD）升高。结论CALALG-Resv-ASCs水凝胶在体内具有促进伤口修复和抗衰老的作用。ASCs和白藜芦醇在海藻酸钙系统中的结合为开发旨在促进皮肤再生和防止组织退化的多功能生物材料提供了有希望的基础。

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引用次数: 0

Tanshinone IIA and quercetin loaded nanoemulsion-thermogel composite system for enhanced acne management: In-vitro/ in-vivo evaluation 丹参酮IIA和槲皮素负载纳米乳剂-热凝胶复合系统增强痤疮管理：体外/体内评价

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-11 DOI: 10.1016/j.jddst.2025.107918

Haiyun Zhang , Xiujuan Wang , Yilun Wang , Yuanyuan Zhao , Yibing Chen , Yuanlu Cui , Qiangsong Wang

The combination of Tanshinone IIA (Tan IIA) and quercetin (QU) demonstrates therapeutic potential for acne treatment. However, their poor water solubility and limited epidermal permeation hinder their effective deposition and delivery within the skin. A novel composite system, referred to as TQ hydrogel, was developed to co-deliver Tan IIA and QU. This system integrated nanoemulsion and thermosensitive gels. The nanoemulsion formulation was optimized through pseudo-ternary phase diagram. The TQ hydrogel was prepared by incorporating a poloxamer-based matrix with the drug-loaded nanoemulsion. The morphology, in vitro drug release profiles, antioxidant capabilities, and antimicrobial efficiency of the TQ hydrogel were assessed. Furthermore, the in vivo anti-acne effects and underlying mechanisms of the TQ hydrogel were evaluated. The prepared nanoemulsion were spherical in shape with a mean particle size of 60 nm and zeta potential was about −8.12 mV. The TQ hydrogel exhibited temperature-triggered sol-gel transition at 30.4 °C. The cumulative release of QU and Tan IIA from TQ hydrogel was 88.69 % and 17.61 % for 24 h, respectively. TQ hydrogel displayed notable antioxidant activity and bactericidal properties. In vivo, TQ hydrogel significantly ameliorated the inflammatory microenvironment of acne tissues, suppressed the expression of androgen receptors (AR), and showed promising potential in reducing acne-induced scarring. TQ hydrogel, as a co-delivery carrier integrating nanoemulsion and thermosensitive gels, represented an ideal platform for acne treatment.

丹参酮IIA （Tan IIA）和槲皮素（QU）的联合应用显示了治疗痤疮的潜力。然而，它们的水溶性差和有限的表皮渗透性阻碍了它们在皮肤内的有效沉积和递送。研究人员开发了一种新型的复合系统，称为TQ水凝胶，该系统将纳米乳液和热敏凝胶结合在一起，共同递送Tan IIA和QU。通过拟三元相图优化了纳米乳液的配方。将波洛莫胺基基质与载药纳米乳结合制备TQ水凝胶。考察了TQ水凝胶的形态、体外药物释放谱、抗氧化能力和抗菌效率。此外，还对TQ水凝胶的体内抗痤疮作用及其机制进行了评价。制备的纳米乳液为球形，平均粒径为60 nm， zeta电位约为−8.12 mV。TQ水凝胶在30.4℃时表现出温度触发的溶胶-凝胶转变。TQ水凝胶24 h的累积释放量分别为88.69%和17.61%。TQ水凝胶具有显著的抗氧化活性和杀菌性能。在体内，TQ水凝胶显著改善痤疮组织的炎症微环境，抑制雄激素受体（AR）的表达，在减少痤疮诱导的瘢痕形成方面显示出良好的潜力。TQ水凝胶作为纳米乳液和热敏凝胶的共递送载体，是治疗痤疮的理想平台。

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引用次数: 0

Repurposing drugs against Leishmania donovani: in vitro efficacy of loratadine and cyproheptadine and their liposomal formulations 重新利用药物治疗多诺瓦利什曼原虫：氯雷他定和赛庚啶及其脂质体制剂的体外疗效

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-09 DOI: 10.1016/j.jddst.2025.107915

Nicky Didwania , Chantal Reigada , Melisa Saye , Claudio A. Pereira , Nahid Ali

In a previous study, we identified the trypanocidal drugs loratadine (LTD) and cyproheptadine (CPH). Both compounds are antihistamines already approved for clinical use. The aim of this work was to evaluate the effectiveness of LTD and CPH for drug repurposing against another protozoan parasite, Leishmania donovani, the causative agent of visceral leishmaniasis. LTD and CPH inhibited promastigote proliferation and amastigote growth in murine peritoneal macrophages. Furthermore, with the aim of improving their leishmanicidal activity, we also formulated liposomes of LTD and CPH, composed of phosphatidylcholine and stearylamine. The liposomal formulations significantly enhanced the efficacy against both promastigotes and intracellular amastigotes, reducing the IC₅₀ values by 5-fold and 2.5-fold, respectively, compared to the free drugs. The reference drug amphotericin B presented a higher effect against these parasites but it remains a second-line drug to treat leishmaniasis because of its high toxicity. The results obtained demonstrate that LTD and CPH liposomes formulations are promising antileishmanial agents, with great potential to be repurposed against L. donovani. Both drugs are approved for human use, which could reduce significantly the requirements for their possible application in the treatment of this neglected disease.

在之前的研究中，我们鉴定出了杀锥虫的药物氯雷他定（LTD）和环己基乙胺（CPH）。这两种化合物都是已经被批准用于临床的抗组胺药。这项工作的目的是评估LTD和CPH对另一种原生动物寄生虫多诺瓦利什曼原虫（内脏利什曼病的病原体）药物再利用的有效性。LTD和CPH抑制小鼠腹膜巨噬细胞中promastigote增殖和amastigote生长。此外，为了提高它们的利什曼尼杀灭活性，我们还配制了由磷脂酰胆碱和硬脂胺组成的LTD和CPH脂质体。脂质体制剂显著增强了对promastigotes和胞内amastigotes的疗效，IC50值分别比游离药物降低了5倍和2.5倍。参考药物两性霉素B对这些寄生虫的作用更高，但由于其高毒性，它仍然是治疗利什曼病的二线药物。结果表明，LTD和CPH脂质体制剂是很有前途的抗利什曼原虫药物，具有很大的潜力用于治疗多诺瓦氏杆菌。这两种药物都已批准供人使用，这可能大大减少它们在治疗这种被忽视疾病方面的应用需求。

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引用次数: 0

Silk fibroin and keratin electrospun nanofibers loaded with acetylsalicylic acid as potential transdermal patches decorated with metallic microneedles 载乙酰水杨酸的丝素蛋白和角蛋白静电纺纳米纤维作为金属微针修饰的潜在透皮贴片

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-09 DOI: 10.1016/j.jddst.2025.107908

Sahra Ezgi Sungu , Bengi Yilmaz Erdemli , Ozge Erdemli , Omer Akturk

Herein, a transdermal patch composed of silk fibroin (SF) and keratin (K) fibers was developed with electrospinning and then loaded with acetylsalicylic acid (ASA) drug and integrated with metallic microneedles for enabling a minimally invasive, pain free application providing high drug release, prone to rapid mixing into the systemic circulation via the dermal route, alternative to hypodermic needles. Fiber diameters around 1 μm were obtained, decreasing significantly to nanofiber size with the presence of keratin. The ethanol (EtOH) treatment rendered the pore sizes more uniform and caused structural changes in the amide bands (transformations from random coil/α-helix to β-sheet structure). The aqueous stability of groups varied between 8 and 9 % (weight loss) and the water uptake (10–16 times their dry weight) and hydrophilicity abilities of groups were high. The amount of keratin had a remarkable influence on mechanical characteristics, tending to increase the brittleness of the structure, while the group without keratin could elongate more. The hand-made design of microneedles (500–1000 μm) allowed high penetration depths and thus the drug permeation and drug release rate enhanced dramatically in microneedle patches that can compete with the free drug. Finally, L929 fibroblast cell viability tests by MTT assay, and seeding studies confirmed that all test groups have cell viability greater than 94 % and desirable cell adhesion, spreading, and proliferation behavior. The developed transdermal skin patches integrated with microneedles might be promising candidates in future clinical applications with their improved physicochemical properties suitable for ASA loading and release, and biocompatibility.

本研究采用静电纺丝技术开发了一种由丝素蛋白（SF）和角蛋白(K)纤维组成的透皮贴片，然后加载乙酰水杨酸（ASA）药物，并与金属微针结合，实现了微创、无痛的应用，药物释放高，易于通过皮肤途径快速混合进入体循环，可替代皮下注射针头。得到的纤维直径约为1 μm，随着角蛋白的存在，纳米纤维的尺寸显著减小。乙醇（EtOH）处理使孔径更加均匀，并引起酰胺带的结构变化（从随机线圈/α-螺旋结构转变为β-片状结构）。各组的水稳定性在8% ~ 9%（失重）之间变化，吸水性（10 ~ 16倍于其干重）和亲水性都很高。角蛋白的添加量对结构的力学特性有显著影响，倾向于增加结构的脆性，而不添加角蛋白的组可以拉长。手工设计的微针（500 ~ 1000 μm）具有较高的穿透深度，从而大大提高了微针贴片的药物渗透和药物释放速度，可以与游离药物竞争。最后，通过MTT法进行L929成纤维细胞活力测试和播种研究证实，所有实验组的细胞活力均大于94%，具有理想的细胞粘附、扩散和增殖行为。所开发的微针透皮贴片具有较好的理化性能，适合ASA的加载和释放，且具有良好的生物相容性，在未来的临床应用中具有广阔的应用前景。

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引用次数: 0

Spin freeze-drying in continuous biomanufacturing: Boon or mirage? 连续生物制造中的自旋冷冻干燥：福音还是海市蜃楼？

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2025-12-09 DOI: 10.1016/j.jddst.2025.107909

Teja Kumar Ponduri , G.S.N. Koteswara Rao

Spin freeze-drying (SFD) has emerged as a potential breakthrough in pharmaceutical lyophilization. It promises over 90 % reductions in cycle time and is compatible with continuous aseptic manufacturing. SFD generates thin frozen films through centrifugal spreading and improves sublimation and desorption with radiative heating. This approach fundamentally changes heat and mass transfer compared to traditional shelf-based drying. Mechanistic studies connect thin-film structure to sublimation flux, desorption speed, and interactions between excipients and proteins. Case studies involving monoclonal antibodies, viral vectors, and mRNA–lipid nanoparticles show opportunities for better stability and quicker processing. On the manufacturing side, SFD introduces new ideas for batch definition, container and closure interactions, and aseptic assurance. It requires integrating process analytical technologies (PAT), mechanistic modeling, and digital twin control. Regulatory translation must consider Quality by Design (QbD) principles and ICH Q13 guidelines for continuous manufacturing. While the potential benefits of SFD for biopharma are clear, like shorter cycles and smaller footprints, risks still exist. These include unproven industrial scalability, regulatory uncertainty, and challenges in optimizing specific formulations. The future of SFD will depend on whether mechanistic control, PAT-enabled validation, and regulatory acceptance can come together to support routine GMP use. If successful, SFD could become a key part of next-generation continuous biomanufacturing; if not, its use may stay limited to specific areas.

自旋冷冻干燥（SFD）已成为制药冻干的潜在突破。它承诺减少90%以上的周期时间，并与连续无菌生产兼容。SFD通过离心扩散产生冷冻薄膜，并通过辐射加热改善升华和解吸。与传统的架子干燥相比，这种方法从根本上改变了传热和传质。机理研究将薄膜结构与升华通量、解吸速度以及赋形剂和蛋白质之间的相互作用联系起来。涉及单克隆抗体、病毒载体和mrna -脂质纳米颗粒的案例研究显示了更好的稳定性和更快的处理机会。在制造方面，SFD引入了批定义，容器和封闭相互作用以及无菌保证的新想法。它需要集成过程分析技术（PAT）、机械建模和数字孪生控制。法规翻译必须考虑设计质量（QbD）原则和连续生产ICH Q13指南。虽然SFD对生物制药的潜在好处是显而易见的，比如更短的周期和更小的足迹，但风险仍然存在。其中包括未经证实的工业可扩展性、监管不确定性以及优化特定配方的挑战。SFD的未来将取决于机械控制、pat支持的验证和监管接受是否能够共同支持常规GMP使用。如果成功，SFD将成为下一代连续生物制造的关键部分；否则，它的使用可能仅限于特定领域。

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引用次数: 0