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Multifunctional fluorescent magnetic molecularly imprinted polymer for curcumin delivery: in vivo wound healing, antibacterial activity, and in silico pharmacokinetic evaluation 姜黄素传递的多功能荧光磁性分子印迹聚合物:体内伤口愈合,抗菌活性和硅药代动力学评价
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-07 DOI: 10.1016/j.jddst.2026.107980
Zeeshan Ali , Nadeem Raza , Muhammad Hayat , Hafiz Muhammad Usman Abid , Abdelmonaim Azzouz , Bouchra Rossafi , Imad Hammoudan , Anis Ahmad Chaudhary , Mohamed Khairy , Mohamed Abdel-Megid
Molecularly imprinted polymers (MIPs) stand out in various biomedical realms as potent and expanding nanoplatforms. This research employed a surface molecular imprinting approach, in which a polydopamine shell was polymerized around Fe3O4@SiO2@FITC nanoparticles in the presence of curcumin (template). After template removal, surface-exposed recognition sites complementary to curcumin were formed, confirming successful imprinting. The synthesized fluorescent magnetic MIPs (FMMIPs) exhibited significant drug loading capacity and responsiveness to magnetic fields, serving as efficient carriers for CUR delivery. Characterization of FMMIPs was executed through FTIR, SEM, TGA, XRD, vibrating sample magnetometry, and dynamic light scattering. The magnetization value of FMMIP was measured at 0.045 emu/g, underscoring its robust magnetic responsiveness to external fields. In-vivo studies for CUR loading and release unveiled that under tissue conditions (pH 5 and 41 °C) a maximal CUR release of 71.33 % occurred, following a sustained profile, compared to the standard physiological environment (pH 7.4 and 37 °C). In diabetic rats, treatment with FMMIP-CUR resulted in 97.55 % wound healing, surpassing the standard treatment with silver sulfadiazine. Histopathological evaluations further confirmed marked enhancements in re-epithelialization, fibroblast activity, and angiogenesis in diabetic wounds after 12 days of treatment. To explore the antibacterial potential of CUR, molecular docking and molecular dynamics (MD) simulations were conducted against P. aeruginosa (4KQR) and S. aureus (3Q8U) targets. CUR exhibited stronger binding affinities compared to ciprofloxacin, forming stable hydrogen bonds and hydrophobic interactions with key residues. The MD simulations over 100 ns revealed greater interaction stability and diversity in the 4KQR–CUR complex, while CUR's interaction with 3Q8U was more dynamic. ADMET predictions confirmed favorable pharmacokinetics and drug-likeness for both compounds, with CUR showing good oral bioavailability, moderate solubility, low toxicity, and acceptable metabolic profiles. The adsorption of CUR onto FMMIPs followed the Freundlich isotherm model (R2 = 0.991) indicating heterogeneous surface binding and the presence of multiple adsorption sites with varying affinities. These results demonstrate FMMIP nanocarrier's potential as a viable option for antidiabetic drug delivery systems.
分子印迹聚合物(MIPs)作为一种强大的、不断扩展的纳米平台,在各种生物医学领域脱颖而出。本研究采用表面分子印迹方法,在姜黄素(模板)存在下,聚多巴胺壳在Fe3O4@SiO2@FITC纳米颗粒周围聚合。模板去除后,形成与姜黄素互补的表面暴露的识别位点,证实印迹成功。合成的荧光磁性MIPs (FMMIPs)具有显著的载药能力和对磁场的响应性,是CUR递送的有效载体。通过FTIR, SEM, TGA, XRD,振动样品磁强计和动态光散射对FMMIPs进行了表征。FMMIP的磁化值为0.045 emu/g,表明其对外部磁场具有较强的响应能力。体内研究表明,在组织条件下(pH 5和41°C),与标准生理环境(pH 7.4和37°C)相比,在持续的情况下,CUR的最大释放量为71.33%。在糖尿病大鼠中,FMMIP-CUR治疗的伤口愈合率为97.55%,超过了磺胺嘧啶银的标准治疗。组织病理学评估进一步证实,治疗12天后,糖尿病伤口的再上皮化、成纤维细胞活性和血管生成明显增强。为探索CUR的抗菌潜力,对铜绿假单胞菌(P. aeruginosa, 4KQR)和金黄色葡萄球菌(S. aureus, 3Q8U)靶点进行了分子对接和分子动力学(MD)模拟。与环丙沙星相比,CUR表现出更强的结合亲和力,与关键残基形成稳定的氢键和疏水相互作用。超过100 ns的MD模拟显示,4KQR-CUR复合物具有更大的相互作用稳定性和多样性,而CUR与3Q8U的相互作用更具动态性。ADMET预测证实了两种化合物良好的药代动力学和药物相似性,CUR具有良好的口服生物利用度、中等溶解度、低毒性和可接受的代谢谱。CUR在FMMIPs上的吸附符合Freundlich等温模型(R2 = 0.991),表明其表面结合不均匀,存在多个不同亲和力的吸附位点。这些结果证明了FMMIP纳米载体作为抗糖尿病药物递送系统的可行性。
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引用次数: 0
Liposomal delivery of Ropivacaine prepared with dextran sulfate as drug-trapping polymer agent for long-acting anesthesia 以硫酸葡聚糖为捕集剂制备罗哌卡因的长效麻醉脂质体研究
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-06 DOI: 10.1016/j.jddst.2026.107983
Rifda Tarimi Octavia , Retno Sari , Ira Sari Yudaniayanti , Dewi Melani Hariyadi , Dwi Setyawan , Gwan Young Kim , Ji Yeon Heo , Gwangheum Yoon , Ahreum Choi , Qonita Kurnia Anjani , Andang Miatmoko
The main problem invariably faced by post-operative patients is persistent pain lasting several days which affects their quality of life. Therefore, therapy providing prolonged analgesic effects is required. Rop is a group of local anesthetics offering a safer alternative to non-opioid analgesics. This study aims to develop and optimize Ropivacaine (Rop)-loaded liposome using Dextran Sulfate as a trapping polymer to enable a sustained release effect. Liposomes were composed of hydrogenated soya phosphatidylcholine and cholesterol and prepared by using the thin-film method. Optimization parameters included drug-to-lipid (D/L) ratios of 1:1 and 1:3, and incubation times of 10, 20, and 30 min. The optimized formulation (D/L ratio 1:1 and 10-min incubation) resulted in a particle size of 177.8 ± 3.82 nm, a PDI of 0.193 ± 0.01, zeta potential of −6.89 ± 4.22 mV, and an encapsulation efficiency of 72.14 ± 1.96 %. In vivo pain behavior was assessed in a postoperative mouse model using a hot plate test at 55 °C. The Rop liposome formulation provided effective analgesia, maintaining % Maximum Possible Effect (%MPE) values above 50 % for up to 8 h longer compared to free Rop with rapid onset within 1 h. The effect was sustained for up to 72 h without adverse reactions. The ability of the liposomal formulation to alleviate chronic pain was also demonstrated by the reduced levels of TNF-α and IL-6 in the postoperative mouse model compared to those of free Rop. In conclusion, the use of Dextran Sulfate has successfully improved the long-acting anesthesia effect of Rop-loaded liposomes.
术后患者面临的主要问题是持续数日的疼痛,影响患者的生活质量。因此,需要提供持久镇痛效果的治疗。Rop是一组局部麻醉剂,为非阿片类镇痛药提供了一种更安全的选择。本研究旨在以硫酸葡聚糖为捕集聚合物,开发并优化罗哌卡因(Ropivacaine, Rop)负载脂质体,使其具有缓释效果。采用薄膜法制备了氢化大豆磷脂酰胆碱脂质体和胆固醇脂质体。优化参数为药脂比(D/L)为1:1和1:3,孵育时间为10、20、30 min。优化后的配方(D/L比为1:1,孵育时间为10 min)制备出粒径为177.8±3.82 nm, PDI为0.193±0.01,zeta电位为- 6.89±4.22 mV,包封率为72.14±1.96%。术后小鼠模型采用55°C热板试验评估体内疼痛行为。Rop脂质体配方提供了有效的镇痛作用,与自由Rop相比,在1小时内快速起效,将%最大可能效应(%MPE)值维持在50%以上长达8小时。效果持续长达72小时,无不良反应。与游离Rop相比,术后小鼠模型中TNF-α和IL-6水平的降低也证明了脂质体制剂减轻慢性疼痛的能力。综上所述,葡聚糖硫酸酯的使用成功地改善了rop负载脂质体的长效麻醉效果。
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引用次数: 0
Self nano-emulsifying drug delivery system based delivery of ketamine for enhanced therapeutic efficacy through behavioral performance in animal model 基于自纳米乳化给药系统的氯胺酮给药,通过动物模型的行为表现提高治疗效果
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-06 DOI: 10.1016/j.jddst.2026.107990
Muhammad I. Afridi , Abdul Jabbar , Muhammad Naseer Abbas , Aziz Balouch , Kausar Amir , Tasmania Kanwal , Huma Ikram , Amjad Khan , Muhammad R. Shah , Sirajuddin , Abdulaziz K. Al Mouslem , Ghallab Alotaibi
Ketamine drug has gained substantial interest owing to its potential for treating depression and chronic pain but its short half-life in body makes it less effective. This study was aimed at enhancing the therapeutic efficacy and safe use of anesthetic, analgesic, and antidepressant drug ketamine for its controlled drug release through self–nanoemulsifying drug delivery system (SNEDDS), following oral administration. Different excipients including Tween 80, cinnamon oil, and propylene glycol with concentration, 30 %, 53.33 %, and 16.67 %, respectively were selected for optimized SNEDDs formulation. All the developed formulations were evaluated for their droplet morphology, zeta potential, size, size distribution, robustness to dilution and thermodynamic stability. Animal studies including Skinner's box activity, open field activity, light dark box activity, plus elevated maze test, forced swim test, hot plate test and novel object recognition test, were carriedout as per standard protocol. Pharmacokinetics analysis was carried out in animal model. KT-SNEDDS demonstrated stability in pH 6.8 buffer with 1000 times dilution without precipitation or phase separation. Less than 100 nm globule size of KT-SNEDDS in solution depicted excellent flow properties. For all tests conducted on animals among all treatment groups KT-SNEDDs proved to be the best with 0.5 mg/kg dose for 12 days. In-vitro study demonstrated controlled and persistent release of 30–84 % drug through KT-SNEDDs as compared to burst release of 60–88 % free KT for 1–12h. In-vivo phamacokinetic study of KT-SNEDDS exhibited maximum time (Tmax) of 4h with maximum residence time (MRT), 4.654h and maximum concentration (Cmax), 339.995 μg/mL with initial dosage of 0.5 mg/kg body weight as compared to free KT with Tmax of 2h, MRT, 2.637h and Cmax, 253.587 μg/mL despite initial dosage of 1 mg/kg body weight. It is concluded from the study that the developed KT-SNEDDS showed better pharmaceutical, pharmacological and pharmacokinetics results, which will lead to its better therapeutic efficacy.
氯胺酮药物由于其治疗抑郁症和慢性疼痛的潜力而获得了极大的兴趣,但其在体内的半衰期短使其效果不佳。本研究旨在提高麻醉、镇痛和抗抑郁药物氯胺酮口服后通过自纳米乳化给药系统(SNEDDS)控制药物释放的疗效和安全性。以Tween 80、肉桂油和丙二醇为辅料,分别以30%、53.33%和16.67%的浓度对sndd进行优化。对所开发的配方进行了液滴形态、zeta势、尺寸、尺寸分布、稀释稳健性和热力学稳定性的评价。动物实验包括斯金纳箱实验、开阔场地实验、明暗箱实验、加高架迷宫实验、强迫游泳实验、热板实验和新物体识别实验。在动物模型上进行药代动力学分析。KT-SNEDDS在pH 6.8的缓冲液中稳定,稀释1000倍,无沉淀或相分离。在溶液中,小于100纳米的KT-SNEDDS具有优异的流动性能。在所有治疗组中进行的所有动物试验中,kt - snedd以0.5 mg/kg剂量持续12天的效果最好。体外研究表明,与60 - 88%游离KT的爆发释放1-12h相比,KT- snedd通过30 - 84%的药物有控制和持续释放。在体内药代动力学研究中,KT- snedds的最大时间(Tmax)为4h,最大停留时间(MRT)为4.654h,最大浓度(Cmax)为339.995 μg/mL,初始剂量为0.5 mg/kg体重,与游离KT相比,Tmax为2h, MRT为2.637h, Cmax为253.587 μg/mL,初始剂量为1 mg/kg体重。本研究表明,研制的KT-SNEDDS具有较好的药理学、药理学和药代动力学结果,这将使其具有较好的治疗效果。
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引用次数: 0
Disulfiram-loaded nanoemulsions for enhanced anticancer efficacy in peritoneal carcinomatosis: Design, optimization, in vitro and in vivo evaluation 负载双硫仑的纳米乳剂增强腹膜癌的抗癌效果:设计、优化、体外和体内评价
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-06 DOI: 10.1016/j.jddst.2026.107994
Ping Wang , Yue Wang , Changjiang Li , Zhongcheng Ke , Yan Gong , Boyuan Liu , Meng Wang , Xiangqun Jin
Disulfiram (DSF), an FDA-approved anti-alcoholism drug, has demonstrated potent anticancer activity against peritoneal carcinomatosis. However, its therapeutic potential is severely hampered by poor aqueous solubility and instability. Nanoemulsion system provides a promising platform to overcome these challenges. Herein, this study developed and optimized a DSF-loaded nanoemulsions (DSF-NE) to enhance the therapeutic efficacy of DSF in peritoneal carcinomatosis. The optimized DSF-NE exhibited several formulation advantages, including a small particle size (∼84 nm), narrow size distribution (∼0.1), high encapsulation efficiency (>90 %) and sustained-release behavior. Subsequently, cytotoxicity assays against MGC-803, SKOV-3 and Caco-2 cells revealed that DSF-NE significantly enhanced cytotoxic effects compared to DSF, with IC50 values reduced by 74 %, 62 % and 56 %, respectively. Consistently, DSF-NE achieved a tumor inhibition rate 108.57 % higher than that of DSF in a murine peritoneal carcinomatosis model. The main mechanism involves enhanced cellular uptake of DSF-NE, which promotes ROS generation and subsequently triggers apoptosis. Collectively, these findings highlight DSF-NE as a nanoformulation strategy that not only improves the therapeutic performance of DSF in peritoneal carcinomatosis but also offers broader implications in the development of effective delivery systems for poorly soluble and unstable drugs.
双硫仑(DSF)是一种fda批准的抗酒精中毒药物,已经显示出对腹膜癌的有效抗癌活性。然而,其水溶性差和不稳定性严重阻碍了其治疗潜力。纳米乳液系统为克服这些挑战提供了一个有希望的平台。本研究开发并优化了DSF负载纳米乳(DSF- ne),以提高DSF对腹膜癌的治疗效果。优化后的DSF-NE具有多种配方优势,包括粒径小(~ 84 nm)、粒径分布窄(~ 0.1 nm)、包封效率高(> 90%)和缓释性能。随后,对MGC-803、SKOV-3和Caco-2细胞的细胞毒实验显示,DSF- ne与DSF相比显著增强了细胞毒作用,IC50值分别降低了74%、62%和56%。在小鼠腹膜癌模型中,DSF- ne的抑瘤率比DSF高108.57%。主要机制涉及增强细胞对DSF-NE的摄取,从而促进ROS的产生并随后触发细胞凋亡。总的来说,这些发现强调了DSF- ne作为一种纳米制剂策略,不仅可以提高DSF在腹膜癌中的治疗效果,而且还可以为开发难溶性和不稳定药物的有效递送系统提供更广泛的意义。
{"title":"Disulfiram-loaded nanoemulsions for enhanced anticancer efficacy in peritoneal carcinomatosis: Design, optimization, in vitro and in vivo evaluation","authors":"Ping Wang ,&nbsp;Yue Wang ,&nbsp;Changjiang Li ,&nbsp;Zhongcheng Ke ,&nbsp;Yan Gong ,&nbsp;Boyuan Liu ,&nbsp;Meng Wang ,&nbsp;Xiangqun Jin","doi":"10.1016/j.jddst.2026.107994","DOIUrl":"10.1016/j.jddst.2026.107994","url":null,"abstract":"<div><div>Disulfiram (DSF), an FDA-approved anti-alcoholism drug, has demonstrated potent anticancer activity against peritoneal carcinomatosis. However, its therapeutic potential is severely hampered by poor aqueous solubility and instability. Nanoemulsion system provides a promising platform to overcome these challenges. Herein, this study developed and optimized a DSF-loaded nanoemulsions (DSF-NE) to enhance the therapeutic efficacy of DSF in peritoneal carcinomatosis. The optimized DSF-NE exhibited several formulation advantages, including a small particle size (∼84 nm), narrow size distribution (∼0.1), high encapsulation efficiency (&gt;90 %) and sustained-release behavior. Subsequently, cytotoxicity assays against MGC-803, SKOV-3 and Caco-2 cells revealed that DSF-NE significantly enhanced cytotoxic effects compared to DSF, with IC<sub>50</sub> values reduced by 74 %, 62 % and 56 %, respectively. Consistently, DSF-NE achieved a tumor inhibition rate 108.57 % higher than that of DSF in a murine peritoneal carcinomatosis model. The main mechanism involves enhanced cellular uptake of DSF-NE, which promotes ROS generation and subsequently triggers apoptosis. Collectively, these findings highlight DSF-NE as a nanoformulation strategy that not only improves the therapeutic performance of DSF in peritoneal carcinomatosis but also offers broader implications in the development of effective delivery systems for poorly soluble and unstable drugs.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107994"},"PeriodicalIF":4.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of a novel liposome nano-formulation of quercetin with optimized cholesterol level [Lipo-Que] for intravenous administration and in vivo toxicity in mice 新型槲皮素脂质体纳米配方优化胆固醇水平[lipoo - que]静脉给药及小鼠体内毒性评价
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-06 DOI: 10.1016/j.jddst.2026.107984
V. Jenitha , D. David Wilson , G. Monith , Nampalli Babu Kokelavani , Ramachandran , S. Viswanathan , M. Srividhya , Vijay Nandana , V. M. Berlin Grace
Quercetin, a synthetic flavonoid phytochemical, has gained attention for its anti-cancer properties due to its anti-oxidant and anti-inflammatory effects, as well as its molecular actions on cancer signaling pathways. However, the therapeutic efficacy of orally administered quercetin is limited due to metabolic conversions. This study aimed to develop a novel liposomal formulation for quercetin administration via intravenous injection, utilizing thermosensitive phospholipids, cholesterol, polyethylene glycol, and folic acid. Two formulations were created (Lipo-Que 7:2:1 and Lipo-Que 5:4:1) and compared against free quercetin [Free-Que] for in vitro characterization, bioactivity, and biocompatibility. Both formulations were tested for anti-oxidant potency and cytotoxicity on a human lung cancer cell line and normal fetal lung fibroblast cells. The optimized dose of 25 μM quercetin was further analyzed for anti-cancer effects. Results showed that Lipo-Que 7:2:1 had significantly higher antioxidant potency and cytotoxicity (IC50 of 5.10 ± 0.19 μM) compared to Lipo-Que 5:4:1 and Free-Que. The formulations demonstrated high drug entrapment efficiency and confirmed successful encapsulation through HPLC, UV–Vis, and FTIR analyses. Additionally, Lipo-Que 7:2:1 showed enhanced quercetin release at higher temperatures and acidic pH, mimicking the cancer microenvironment. In vivo toxicity studies indicated that Lipo-Que 7:2:1 was safer than Free-Que, with no significant toxic effects observed.

Applications

These findings suggest that optimized liposomal quercetin formulations enhance therapeutic efficacy while maintaining stability under hyperthermic conditions (up to 45 °C). The biocompatibility results support their potential clinical application as intravenous drug candidates for lung cancer treatment.
槲皮素是一种合成的类黄酮植物化学物质,由于其抗氧化和抗炎作用以及在癌症信号通路中的分子作用而受到关注。然而,口服槲皮素的治疗效果是有限的,由于代谢转化。本研究旨在利用热敏磷脂、胆固醇、聚乙二醇和叶酸,开发一种新的槲皮素静脉注射给药脂质体。制备了两种制剂(lipoo - que 7:2:1和lipoo - que 5:4:1),并与游离槲皮素[free - que]进行体外表征、生物活性和生物相容性的比较。在人肺癌细胞系和正常胎儿肺成纤维细胞上测试了两种配方的抗氧化能力和细胞毒性。进一步分析最佳剂量25 μM槲皮素的抗癌作用。结果表明,与lipoo - que 5:4:1和Free-Que相比,lipoo - que 7:2:1具有显著的抗氧化能力和细胞毒性(IC50为5.10±0.19 μM)。通过HPLC、UV-Vis和FTIR分析,证实该制剂具有较高的药物包封效率。此外,Lipo-Que 7:2:1显示在高温和酸性pH下槲皮素释放增强,模拟癌症微环境。体内毒性研究表明lipoo - que 7:2:1比Free-Que更安全,没有观察到明显的毒性作用。这些发现表明,优化的槲皮素脂质体制剂可提高治疗效果,同时在高温条件下(高达45°C)保持稳定性。生物相容性结果支持其作为肺癌静脉注射候选药物的潜在临床应用。
{"title":"Evaluation of a novel liposome nano-formulation of quercetin with optimized cholesterol level [Lipo-Que] for intravenous administration and in vivo toxicity in mice","authors":"V. Jenitha ,&nbsp;D. David Wilson ,&nbsp;G. Monith ,&nbsp;Nampalli Babu Kokelavani ,&nbsp;Ramachandran ,&nbsp;S. Viswanathan ,&nbsp;M. Srividhya ,&nbsp;Vijay Nandana ,&nbsp;V. M. Berlin Grace","doi":"10.1016/j.jddst.2026.107984","DOIUrl":"10.1016/j.jddst.2026.107984","url":null,"abstract":"<div><div>Quercetin, a synthetic flavonoid phytochemical, has gained attention for its anti-cancer properties due to its anti-oxidant and anti-inflammatory effects, as well as its molecular actions on cancer signaling pathways. However, the therapeutic efficacy of orally administered quercetin is limited due to metabolic conversions. This study aimed to develop a novel liposomal formulation for quercetin administration via intravenous injection, utilizing thermosensitive phospholipids, cholesterol, polyethylene glycol, and folic acid. Two formulations were created (Lipo-Que 7:2:1 and Lipo-Que 5:4:1) and compared against free quercetin [Free-Que] for <em>in vitro</em> characterization, bioactivity, and biocompatibility. Both formulations were tested for anti-oxidant potency and cytotoxicity on a human lung cancer cell line and normal fetal lung fibroblast cells. The optimized dose of 25 μM quercetin was further analyzed for anti-cancer effects. Results showed that Lipo-Que 7:2:1 had significantly higher antioxidant potency and cytotoxicity (IC50 of 5.10 ± 0.19 μM) compared to Lipo-Que 5:4:1 and Free-Que. The formulations demonstrated high drug entrapment efficiency and confirmed successful encapsulation through HPLC, UV–Vis, and FTIR analyses. Additionally, Lipo-Que 7:2:1 showed enhanced quercetin release at higher temperatures and acidic pH, mimicking the cancer microenvironment. In vivo toxicity studies indicated that Lipo-Que 7:2:1 was safer than Free-Que, with no significant toxic effects observed.</div></div><div><h3>Applications</h3><div>These findings suggest that optimized liposomal quercetin formulations enhance therapeutic efficacy while maintaining stability under hyperthermic conditions (up to 45 °C). The biocompatibility results support their potential clinical application as intravenous drug candidates for lung cancer treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"117 ","pages":"Article 107984"},"PeriodicalIF":4.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lactoferrin-functionalized bioinspired grapefruit-extracellular vesicles for targeted delivery of pterostilbene in lung cancer therapy 乳铁蛋白功能化的生物启发西柚细胞外囊泡靶向递送紫檀芪在肺癌治疗中
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107991
Eman M. Nour , Salma E. El-Habashy , Ahmed M.R. Fath El-Bab , Basant A. Bakr , Riham M. El-Moslemany , Amal H. El-Kamel
Lung cancer remains the primary cause of cancer-related mortality worldwide, emphasizing the pressing need for novel phytoconstituent-based therapeutic strategies. This study investigates the lung anti-cancer potential of pterostilbene (PS), a bioactive phytochemical, incorporated into a bioinspired delivery system to improve its efficacy. PS was encapsulated within grapefruit-derived extracellular vesicles (GEV) for the development of novel (PS-GEV). Two isolation techniques were investigated: polymer precipitation and a microfluidic-assisted approach, with polymer precipitation offering superior scalability and efficiency. The resulting PS-GEV, isolated using PEG-precipitation, exhibited excellent colloidal stability, a high encapsulation efficiency exceeding 95 %, and a nanoscale particle size (30.85 ± 8.15 nm). To enhance tumor targeting and therapeutic outcomes, lactoferrin functionalization was performed (LF/PS-GEV). These modified nanocarriers showed a zeta potential of −4.03 ± 0.22 mV, particle size of 48.49 ± 13.14 nm, and a sustained release profile with 59.3 ± 4.93 % PS release over 24 h. In vitro studies on A549 lung cancer cells demonstrated enhanced cellular uptake, reduced cell viability, and inhibited cancer cell migration. The developed vesicles demonstrated high hemocompatibility. In vivo evaluation in a urethane-induced lung cancer mouse model confirmed improved therapeutic outcomes, with LF/PS-GEV treatment significantly reducing the tumor weight-to-body weight ratio (5.05 ± 0.37) compared to the untreated group. Additionally, pro-angiogenic (VEGF) and proliferative markers (cyclin D1) were downregulated, while apoptotic markers BAX (1.89 ± 0.04-fold) and caspase-3 (4.91 ± 0.09-fold) were upregulated. Histological and immunohistochemical analyses confirmed notable suppression of chemotherapy resistance-related p53 protein. Collectively, these findings highlight LF/PS-GEV as a potent, active targeting nanotherapeutic platform for effective lung cancer management through enhanced therapeutic efficacy and tumor-specific action.
肺癌仍然是世界范围内癌症相关死亡的主要原因,强调迫切需要新的基于植物成分的治疗策略。本研究探讨了紫檀芪(pterostilbene, PS)作为一种具有生物活性的植物化学物质,加入到生物激励给药系统中,以提高其抗肺癌的潜力。PS被包裹在葡萄柚源性细胞外囊泡(GEV)中,用于开发新的(PS-GEV)。研究了两种分离技术:聚合物沉淀法和微流体辅助方法,其中聚合物沉淀法具有优越的可扩展性和效率。通过聚乙二醇沉淀法分离得到的PS-GEV具有优异的胶体稳定性,包封效率超过95%,粒径为纳米级(30.85±8.15 nm)。为了提高肿瘤靶向性和治疗效果,进行了乳铁蛋白功能化(LF/PS-GEV)。这些修饰的纳米载体的zeta电位为- 4.03±0.22 mV,粒径为48.49±13.14 nm, 24小时的缓释率为59.3±4.93%。在体外对A549肺癌细胞的研究表明,细胞摄取增强,细胞活力降低,癌细胞迁移受到抑制。发育的囊泡表现出高度的血液相容性。在氨基甲酸乙酯诱导的肺癌小鼠模型中进行的体内评估证实了治疗效果的改善,与未治疗组相比,LF/PS-GEV治疗显著降低了肿瘤重量与体重比(5.05±0.37)。促血管生成(VEGF)和增殖标志物(cyclin D1)下调,凋亡标志物BAX(1.89±0.04倍)和caspase-3(4.91±0.09倍)上调。组织学和免疫组织化学分析证实化疗耐药相关p53蛋白明显抑制。总之,这些发现突出了LF/PS-GEV作为一种有效的、活性靶向的纳米治疗平台,通过增强治疗效果和肿瘤特异性作用,有效地管理肺癌。
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引用次数: 0
Effect of ionizable lipid head and tail group modification on mRNA delivery efficiency 可电离脂质头尾基团修饰对mRNA传递效率的影响
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107981
Soan Park , Kanghun Lee , Hyun-Jung An , Enhui Lin , Sugyeom Kim , Hyeongseok Kim , Siheon Jeong , Snehagni Roy , Yeon Woo Kang , Jaehyuk Yang , Seung-Woo Lee , Gi-Ra Yi , Hyomin Lee , Dong-won Seo , Dong Soo Hwang , Joongoo Lee , Jeong Wook Lee
Ionizable lipids are crucial components of lipid nanoparticles (LNPs) that significantly impact mRNA therapeutic delivery efficiency. While SM-102 and ALC-0315 demonstrated success in Moderna and Pfizer/BioNTech COVID-19 vaccines, the relationship between their structural features and delivery performance remains unclear. We systematically modified SM-102 by incorporating ALC-0315 features: converting its asymmetric tail to a symmetric structure and replacing the 2-aminoethanol head group with ALC-0315's 4-aminobutanol group. Both modifications decreased mRNA delivery efficiency in vitro and in vivo compared to unmodified SM-102. To investigate the underlying mechanisms, we conducted independent labeling assays using DiI to track LNP internalization, and Cy3 to monitor mRNA cargo delivery. Our results revealed that while tail-modified LNPs exhibited rapid and sustained cellular uptake (DiI signal), head-modified LNPs showed relatively lower internalization. Interestingly, despite the lower uptake, the head-modified LNPs achieved significantly higher GFP expression. These findings demonstrate a clear discrepancy between internalization quantity and translation efficiency. We conclude that the absolute amount of internalized mRNA is not the sole determinant of delivery success; rather, the effective translation (functional delivery) is more critical. This study suggests that LNP structural optimization should prioritize post-internalization functional release and translation quality over simple uptake efficiency.
可电离脂质是脂质纳米颗粒(LNPs)的重要组成部分,它显著影响mRNA的治疗递送效率。虽然SM-102和ALC-0315在Moderna和辉瑞/BioNTech的COVID-19疫苗中取得了成功,但它们的结构特征与递送性能之间的关系尚不清楚。我们将ALC-0315的不对称尾部转化为对称结构,并用ALC-0315的4-氨基丁醇基团取代2-氨基乙醇基团,对SM-102进行了系统的修饰。与未修饰的SM-102相比,这两种修饰都降低了mRNA在体外和体内的传递效率。为了研究潜在的机制,我们进行了独立的标记分析,使用DiI来跟踪LNP的内化,使用Cy3来监测mRNA的货物递送。我们的研究结果显示,虽然尾部修饰的LNPs表现出快速和持续的细胞摄取(DiI信号),但头部修饰的LNPs表现出相对较低的内化。有趣的是,尽管摄取较低,头部修饰的LNPs获得了显著更高的GFP表达。这些研究结果表明,内化量与翻译效率之间存在明显的差异。我们得出结论,内化mRNA的绝对数量不是递送成功的唯一决定因素;相反,有效的翻译(功能交付)更为关键。本研究表明,LNP结构优化应优先考虑内化后的功能释放和翻译质量,而不是简单的吸收效率。
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引用次数: 0
Fabrication of hairpin DNA-functionalized polydopamine-coated gold nanoparticles as a theranostic nanoplatform for effective delivery of daunorubicin: Binding affinity, drug release and cytotoxicity study 发夹dna功能化聚多巴胺包覆金纳米颗粒作为柔红霉素有效递送治疗纳米平台的制备:结合亲和力、药物释放和细胞毒性研究
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107982
Jie Liu , Xiangtai Wang , Yushu Wu , Lixia Yuan , Xiusheng Zhang , Xiaoyan Wu , Min Liu
Enhanced drug efflux in breast cancer cells is mediated by multiple transporters (e.g., P-glycoprotein), and the breast cancer resistance protein (BCRP) represents a key biomarker and therapeutic target among them. To address this, we constructed a pH-responsive multifunctional nanocarrier, hpDNA-PDA-AuNPs, by functionalizing polydopamine-coated gold nanoparticles with hairpin DNA (hpDNA) to deliver daunorubicin (DAU). This system integrated diagnostic imaging with three therapeutic modalities: chemotherapy, gene therapy, and photothermal therapy. It demonstrated specific targeting toward BCRP mRNA, achieving a detection limit of 0.64 nM. Spectroscopic and calorimetric analyses revealed that DAU binds more strongly to hpDNA-PDA-AuNPs than to PDA-AuNPs, which was attenuated under acidic conditions. The hpDNA-PDA-AuNPs + DAU system exhibited pH-responsive drug release, enhanced by NIR irradiation and BCRP mRNA. The combined treatment demonstrated potent synergistic antitumor activity with nuclear accumulation of DAU, offering a promising platform to overcome multidrug resistance via programmable drug release, gene silencing, and photothermal ablation.
乳腺癌细胞内药物外排增强是由多种转运蛋白(如p -糖蛋白)介导的,其中乳腺癌耐药蛋白(breast cancer resistance protein, BCRP)是关键的生物标志物和治疗靶点。为了解决这个问题,我们构建了一个ph响应的多功能纳米载体,hpDNA- pda - aunps,通过发夹DNA (hpDNA)功能化聚多巴胺包被的金纳米颗粒来传递柔红霉素(DAU)。该系统将诊断成像与三种治疗方式相结合:化疗、基因治疗和光热治疗。对BCRP mRNA具有特异性靶向作用,检测限为0.64 nM。光谱分析和量热分析表明,DAU与hpDNA-PDA-AuNPs的结合比与PDA-AuNPs的结合更强,在酸性条件下减弱。hpDNA-PDA-AuNPs + DAU系统表现出ph响应性药物释放,近红外照射和BCRP mRNA增强了药物释放。联合治疗显示出强大的协同抗肿瘤活性和核累积的DAU,提供了一个有前途的平台,通过可编程的药物释放,基因沉默和光热消融克服多药耐药。
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引用次数: 0
Dual release of miRNA-424-3p and doxorubicin using layer-by-layer stimuli-responsive dendritic mesoporous nanoparticles 利用一层一层的刺激响应树突状介孔纳米颗粒双重释放miRNA-424-3p和阿霉素
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107986
Oznur Akbal Vural , Tayfun Vural , Vicente Martí-Centelles , Estela Climent , Alba García-Fernández , Ramón Martínez-Máñez
The prevalence of cancer is on the rise on a global scale, and lung cancer represents one of the most common types of cancer worldwide that leads to high cancer-related deaths. Over the past decade, nanotechnology has made tremendous progress in cancer treatment. Moreover, combination therapy, including chemotherapy and gene therapy, has turned out to be a promising strategy that could enhance therapeutic efficacy in the treatment of lung adenocarcinoma. The tumor-suppressive miRNA-424-3p has demonstrated to significantly downregulate galectin-3 (Gal3) which is an anti-apoptotic protein and highly expressed in A549 cells. This has been shown to promote apoptosis, decrease proliferation, and increase sensitivity to the chemotherapeutic drug doxorubicin (Dox). However, miRNA-424-3p-based combination therapies with Dox have not yet been reported. Since dendritic mesoporous silica nanoparticles (DMSNs) have the potential to act as carriers for nucleic acids and drugs simultaneously, in this study we have successfully introduced for the first time anti-Gal3 functionalized DMSNs for the co-delivery of miRNA-424-3p and Dox protected with a layer-by-layer polyethyleneimine and poly-L-lysine coating. Whereas there is no or minimal Dox and miRNA release under neutral pH from the nanoparticles, conversely, a significant delivery of Dox and miRNA is seen in lysosomal extract medium. The effects of the co-delivery system, i.e. miRNA-424-3p and Dox, on A549 cells is evaluated by analyzing cell proliferation, cellular uptake, cell apoptosis assay, and the expression of related proteins and genes. The results demonstrate that miRNA-424-3p effectively transfected into A549 lung cancer cells, dramatically reducing the expression of Gal3 at the protein level. Forward transfection of the cell line with the DMSN loaded with miRNA-424-3p and Dox causes both a decrease in cell viability and an increase in apoptosis induction. Our data shows that the designed DMSN has a good performance as a combined drug and gene delivery system for cancer therapy.
癌症的患病率在全球范围内呈上升趋势,肺癌是全球最常见的癌症类型之一,导致与癌症相关的高死亡率。在过去的十年里,纳米技术在癌症治疗方面取得了巨大的进步。此外,包括化疗和基因治疗在内的联合治疗已被证明是一种有前途的策略,可以提高治疗肺腺癌的疗效。肿瘤抑制miRNA-424-3p已被证明可显著下调半乳糖凝集素-3 (Gal3), Gal3是一种在A549细胞中高表达的抗凋亡蛋白。这已被证明可以促进细胞凋亡,减少增殖,并增加对化疗药物阿霉素(Dox)的敏感性。然而,基于mirna -424-3p与Dox的联合治疗尚未报道。由于树突状介孔二氧化硅纳米颗粒(DMSNs)具有同时作为核酸和药物载体的潜力,在本研究中,我们首次成功地引入了抗gal3功能化的DMSNs,用于共同递送miRNA-424-3p和Dox,并使用一层一层的聚乙烯亚胺和聚l -赖氨酸涂层保护。在中性pH下,纳米颗粒没有或只有很少的Dox和miRNA释放,相反,在溶酶体提取物培养基中可以看到Dox和miRNA的大量释放。通过分析细胞增殖、细胞摄取、细胞凋亡实验以及相关蛋白和基因的表达,评估miRNA-424-3p和Dox共递送系统对A549细胞的影响。结果表明,miRNA-424-3p有效转染A549肺癌细胞,在蛋白水平上显著降低Gal3的表达。负载miRNA-424-3p和Dox的dmn正向转染细胞系可导致细胞活力下降和细胞凋亡诱导增加。我们的数据表明,所设计的DMSN作为一种药物和基因联合传递系统在癌症治疗中具有良好的性能。
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引用次数: 0
Microalgae-derived vesicles as potential carriers for therapeutic biomacromolecules 微藻衍生囊泡作为治疗性生物大分子的潜在载体
IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2026-01-05 DOI: 10.1016/j.jddst.2026.107985
Mária Klacsová , Krisztina Sebők-Nagy , Tibor Páli , Marcela Chovancová , László Almásy , Daniela Uhríková
Microalgae-derived vesicles (AGVs) were investigated as potential carriers for therapeutic biomacromolecules. AGVs were prepared by rehydration of a lyophilisate of proteolipid ghost membranes from Dunaliella tertiolecta and subsequent extrusion or sonication. Based on our results, extrusion is suggested to be a more suitable method because of the low loss of the lipid and protein content. Applying small-angle neutron scattering and dynamic and electrophoretic light scattering, we found that the formed AGVs are spherical, unilamellar, with moderate polydispersity, and a negative surface charge of −27 mV. EPR findings show that they retain the membrane dynamics, and possibly the degree of lipid chain saturation, of the ‘mother’ algal cells. The drug-binding efficiency of the reconstructed AGVs was tested for two model biomacromolecules, DNA and BSA, using an ethidium bromide exclusion assay and tryptophane autofluorescence, respectively. The electrostatic interaction between AGVs and DNA polyanion was mediated by Ca2+ ions, while for the interaction of BSA with AGVs hydrophobic interactions are assumed to play a dominant role. For both macromolecules tested, 40 % binding of the total drug amount was achieved by passive incubation, which indicates that reconstructed AGVs might expand the repertoire of potential delivery systems for therapeutic biomacromolecules.
研究了微藻衍生囊泡(agv)作为治疗性生物大分子的潜在载体。agv是由杜氏藻蛋白脂鬼膜冻干液再水化,然后挤压或超声制备的。根据我们的研究结果,挤出法是一种更合适的方法,因为它的脂肪和蛋白质含量损失较小。采用小角中子散射、动态光散射和电泳光散射等方法研究发现,制备的agv呈球形、单层、多分散性适中,表面负电荷为- 27 mV。EPR结果表明,它们保留了“母”藻细胞的膜动力学,可能还有脂链饱和的程度。采用溴化乙啶排除法和色氨酸自身荧光法分别检测重组agv对DNA和BSA两种模型生物大分子的药物结合效率。agv与DNA多阴离子之间的静电相互作用是由Ca2+离子介导的,而BSA与agv的相互作用被认为是疏水相互作用起主导作用。对于这两种被测试的大分子,通过被动孵育可以达到总药物量的40%,这表明重建的agv可能会扩大治疗性生物大分子的潜在递送系统。
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引用次数: 0
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Journal of Drug Delivery Science and Technology
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