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

Revolutionizing microneedle array fabrication using additive manufacturing technologies: Potential applications and clinical translation 利用增材制造技术革新微针阵列制造：潜在应用和临床转化

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-13 DOI: 10.1016/j.jddst.2024.106288

Rahul Nadda , Prashant Kumar Singh , Diganta Bhusan Das

Microneedle (MN) arrays offer an effective method for drug delivery that is minimally invasive and pain-free, demonstrating significant potential for medical applications. However, manufacturing adequate MN arrays is challenging because they are micron-scale structures and have complicated morphology. Therefore, innovative manufacturing technologies are highly sought after for developing MN arrays, as they would significantly advance their clinical translations. Additive manufacturing has emerged as a groundbreaking technique in the pharmaceutical realm, offering a distinctive capacity to produce personalised dosage forms and patient-tailored medical devices like MNs. Presently, additive manufacturing technology has been used to create MN arrays, which might help increase the usage of these arrays in medical applications and promote the development of new designs. This work aims to review several key additive manufacturing methods that can produce MNs directly from computer 3D models in a single operation. Additionally, it will include an evaluation of their advantages and disadvantages. This study also provides an overview of current research on 3D-printed MN-assisted delivery systems for drugs and explores the parameters that affect the mechanical characteristics of these MNs. To demonstrate the rate of progress in additive manufacturing of MN, a time series analysis of the publication was also carried out using a “single series” autoregressive integrated moving average (ARIMA) forecast. Overall, the review demonstrates that additive manufacturing has excellent potential to create MNs because of its versatility, simplicity, high reproducibility, and accuracy. However, more research will be required in the future to enhance the strength of the printed parts and decrease manufacturing costs.

微针（MN）阵列是一种有效的给药方法，具有微创和无痛的特点，在医疗应用方面具有巨大的潜力。然而，由于微针阵列是微米级结构，形态复杂，因此制造适当的微针阵列具有挑战性。因此，创新制造技术在开发 MN 阵列方面备受追捧，因为这些技术将大大推动 MN 阵列的临床应用。快速成型制造技术已成为制药领域的一项突破性技术，具有生产个性化剂型和患者定制医疗设备（如 MN）的独特能力。目前，增材制造技术已被用于制造 MN 阵列，这可能有助于提高这些阵列在医疗应用中的使用率，并促进新设计的开发。这项工作旨在回顾几种关键的快速成型制造方法，这些方法可直接从计算机三维模型一次性生产 MN。此外，本研究还将评估这些方法的优缺点。本研究还概述了目前有关三维打印 MN 辅助药物输送系统的研究，并探讨了影响这些 MN 机械特性的参数。为了展示 MN 增材制造的进展速度，还使用 "单序列 "自回归综合移动平均（ARIMA）预测对出版物进行了时间序列分析。总之，综述表明，增材制造因其多功能性、简便性、高可重复性和精确性，在制造 MN 方面具有巨大潜力。不过，未来还需要开展更多研究，以提高打印部件的强度并降低制造成本。

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引用次数: 0

Fabrication and evaluation of a biodegradable electrospun chip loaded with chlorhexidine for periodontal disease 制作和评估装有洗必泰的生物可降解电纺芯片，用于治疗牙周病

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-12 DOI: 10.1016/j.jddst.2024.106271

Seongik Hong , Seung-Jin Kim , Joohee Jung

Electrospinning technique is used for the manufacturing matrices of drug delivery systems. This study aimed at fabricating and evaluating an electrospun chip for prolonged retention and controlled drug release at the lesion site. A biodegradable electrospun chip loaded with chlorhexidine (BESC-CHX) was manufactured to treat periodontal diseases. Then, physicochemical properties and efficacy of BESC-CHXs were investigated. The CHX content of BESC was analyzed using high-performance liquid chromatography. The antimicrobial activity and anti-inflammation effects of BESC-CHX were assessed using a disc diffusion assay and a periodontal disease model. BESC-CHX, which is composed of 700 nm fibers, was observed by scanning electron microscopy. Many BESC-CHX batches maintained consistent CHX levels, with a drug entrapment efficiency of 83.3 %. The chip released CHX for seven days and was completely degraded in artificial saliva. BESC-CHX exhibited 99.99 % antimicrobial activity against 11 species of microorganisms. In a beagle periodontal disease model, BESC-CHX demonstrated improvements in periodontal probing depth and clinical attachment level, but these changes were not statistically significant. However, alveolar bone regeneration was observed in cementoenamel junction-alveolar bone crest measurements. The lowest inflammation scores were observed in this group. These findings suggest that BESC-CHXs may be beneficial for the treatment of periodontal disease.

电纺丝技术用于制造给药系统的基质。本研究旨在制造和评估一种电纺芯片，以延长药物在病变部位的保留时间并控制药物释放。研究人员制造了一种负载洗必泰的生物可降解电纺芯片（BESC-CHX），用于治疗牙周疾病。然后，研究了 BESC-CHX 的理化性质和疗效。采用高效液相色谱法分析了 BESC 中的 CHX 含量。采用盘扩散试验和牙周病模型评估了 BESC-CHX 的抗菌活性和抗炎效果。扫描电子显微镜观察了由 700 纳米纤维组成的 BESC-CHX。许多批次的 BESC-CHX 都能保持稳定的 CHX 含量，药物截留效率为 83.3%。该芯片可在七天内释放 CHX，并在人工唾液中完全降解。BESC-CHX 对 11 种微生物具有 99.99% 的抗菌活性。在小猎犬牙周病模型中，BESC-CHX 可改善牙周探诊深度和临床附着水平，但这些变化在统计学上并不显著。不过，在牙本质釉质交界处-牙槽骨嵴测量中观察到了牙槽骨再生。该组的炎症评分最低。这些研究结果表明，BESC-CHX 可用于治疗牙周疾病。

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引用次数: 0

Biocompatible cationic 5-fluorouracil loaded elastic liposomes for ocular delivery: In vitro, ex vivo, and in vivo evaluation 用于眼部给药的生物相容性阳离子 5-氟尿嘧啶负载弹性脂质体：体外、体外和体内评估

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-12 DOI: 10.1016/j.jddst.2024.106278

Mohhammad Ramzan , Tasneem Khan , Mohd Usman Mohd Siddique , Mudassar Shahid

5-fluorouracil (5-FU) is used to treat scleral and episcleral fibroblast proliferations (scarring process) in the eyes. Frequent washing of the conventional solution results in limited drug access to the eyes. Taguchi and central composite design (CCD) oriented optimized mucoadhesive cationic elastic liposomes were prepared and characterized. The optimized F-CEL8 (composed of 85 mg of dipalmitoyl-phosphatidylcholine, 15 mg of sodium cholate, 10 mg of 5-FU, 7 mg of ethanol, and 883 mg of buffer) and its gel were studied for in vitro and ex vivo drug release profiles as compared to the drug solution and the liposomes. In vitro hemolysis and Draize studies corroborated safety concerns. An in vivo pharmacokinetics study was studied in rats. Each mL of F-CEL8 contained dipalmitoyl-phosphatidylcholine (X₁), sodium cholate, and ethanol to deliver 10 mg of 5-FU with optimal vesicle size, low polydispersity index (PDI), and high zeta potential (ZP). The %EE value of spherical F-CEL8 was quite high (82.3 ± 7.1 %) as compared to liposomes (∼53 %) due to the large volume of the inner aqueous chamber of vesicles. F-CEL8-gel exhibited relatively high viscosity for slow and sustained release for 24 h as compared to others. The percent permeation of 5-FU from the solution, F-CEL8, F-CEL8-gel, and the liposomes were found to be 28.6 ± 4.6 %, 69.6 ± 7.4 %, 76.89 ± 12.4 %, and 54.8 ± 5.3 %, respectively. All isotonic formulations did not exhibit hemolysis and irritation to the eyes. The gel illustrated the highest values of pharmacokinetics parameters as compared to the solution and the liposomes, which may be attributed to the maximum residence time achieved through electrostatic interaction (the vesicle internalization with the mucosal layer of eyes).

5-氟尿嘧啶（5-FU）用于治疗眼睛巩膜和巩膜外纤维细胞增生（瘢痕形成过程）。频繁清洗传统溶液会限制药物进入眼睛。本研究制备了以田口和中央复合设计（CCD）为导向的优化粘附性阳离子弹性脂质体，并对其进行了表征。与药物溶液和脂质体相比，研究了优化的 F-CEL8（由 85 毫克二棕榈酰磷脂酰胆碱、15 毫克胆酸钠、10 毫克 5-FU、7 毫克乙醇和 883 毫克缓冲液组成）及其凝胶的体外和体内药物释放曲线。体外溶血和 Draize 研究证实了安全性问题。在大鼠身上进行了体内药代动力学研究。每毫升 F-CEL8 含有二棕榈酰磷脂酰胆碱 (X1)、胆酸钠和乙醇，能以最佳的囊泡大小、低多分散指数 (PDI) 和高 Zeta 电位 (ZP) 输送 10 毫克 5-FU。与脂质体（∼53 %）相比，球形 F-CEL8 的 %EE 值相当高（82.3 ± 7.1 %），这是由于囊泡内水腔的体积较大。与其他凝胶相比，F-CEL8-凝胶的粘度相对较高，可在 24 小时内缓慢持续释放。5-FU 从溶液、F-CEL8、F-CEL8-凝胶和脂质体中的渗透率分别为 28.6 ± 4.6 %、69.6 ± 7.4 %、76.89 ± 12.4 % 和 54.8 ± 5.3 %。所有等渗配方均未出现溶血和对眼睛的刺激。与溶液和脂质体相比，凝胶的药代动力学参数值最高，这可能是由于通过静电作用（囊泡与眼睛粘膜层的内化作用）实现了最长的停留时间。

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引用次数: 0

In situ growth of ZIF-8 on cellulose microspheres with high doxorubicin loading capacity and pH-sensitive for oral drug delivery ZIF-8 在纤维素微球上原位生长，具有高多柔比星负载能力和口服给药的 pH 敏感性

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-11 DOI: 10.1016/j.jddst.2024.106263

Zixuan Zhang , Yaoyao Wang , Simei Wu , Huabing Yuan , Xiaogang Luo

Metal-organic framework (MOF) nanoparticles are a class of porous nanomaterials with wide application prospects. Zeolitic imidazolate framework (ZIF) materials have high loading performance and pH-sensitive characteristics, which means they have great development prospects in the development of drug carrier systems. Herein, cellulose microspheres (CM) were used as a carrier for the nucleation and growth of ZIF-8 nanocrystals. CM@ZIF-8 was prepared in situ, which was more convenient, flexible, cost-effective, and highly safe. CM@ZIF-8, as a novel carrier, was used to monitor the release of the anticancer drug Doxorubicin (DOX) and prevent it from dissipating before reaching its goal. The designed DOX-loaded CM@ZIF-8 (CM@ZIF-8-DOX) system was characterized by FTIR, SEM, N₂ sorption isotherm, XRD, and Cytotoxicity assay (cells survival rate 95.08 %). CM@ZIF-8-DOX exhibited controlled drug release behavior in simulated in-vitro tumor microenvironments (81.2 % drug release throughout 72h). CM@ZIF-8 simultaneously had a high loading capacity of DOX (Q_e = 159.71 mg∙g⁻¹), and the amount released under acidic conditions (pH 5.0) was greater (63.4 % after 15 h) than under neutral conditions (pH 7.4) due to the detachment of the coordination between metal ions and ligands (37.6 % after 15 h).

金属有机框架（MOF）纳米颗粒是一类具有广泛应用前景的多孔纳米材料。沸石咪唑盐酸盐框架（ZIF）材料具有高负载性能和pH敏感性等特点，在药物载体系统的开发中具有广阔的发展前景。本文以纤维素微球（CM）为载体，促进了ZIF-8纳米晶体的成核和生长。CM@ZIF-8采用原位制备，更加方便、灵活、经济、安全。作为一种新型载体，CM@ZIF-8 被用于监测抗癌药物多柔比星（DOX）的释放，并防止其在达到目标之前消散。傅立叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）、N2吸附等温线、X射线衍射（XRD）和细胞毒性试验（细胞存活率为95.08%）对所设计的DOX负载CM@ZIF-8（CM@ZIF-8-DOX）系统进行了表征。在模拟体外肿瘤微环境中，CM@ZIF-8-DOX 表现出可控的药物释放行为（72 小时内药物释放率达 81.2%）。CM@ZIF-8同时具有很高的DOX负载能力（Qe = 159.71 mg∙g-1），在酸性条件（pH 5.0）下的释放量（15小时后为63.4%）大于中性条件（pH 7.4）下的释放量（15小时后为37.6%），这是由于金属离子与配体之间的配位脱离所致。

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引用次数: 0

Biopharmaceutical modulatory effects of newly engineered bile acid-Tyloxapol nanogels for attenuation of cytotoxicity in auditory cells 新设计的胆汁酸-泰乐菌素纳米凝胶对生物制药的调节作用，可减轻听觉细胞的细胞毒性

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-11 DOI: 10.1016/j.jddst.2024.106284

Bozica Kovacevic , Susbin Raj Wagle , Corina Mihaela Ionescu , Thomas Foster , Maja Đanić , Momir Mikov , Armin Mooranian , Hani Al-Salami

This study presents novel thermoresponsive nanogels composed of chenodeoxycholic acid and Tyloxapol for potential inner ear drug delivery. The nanogels exhibit non-Newtonian, shear-thinning fluid behaviour and rapid gelation at body temperature. Biocompatibility studies were conducted on auditory and macrophage cell lines. Nanogels had a minimal impact on cellular viability, glycolysis, and mitochondrial respiration of auditory cells after 24 h of exposure. However, mitochondrial function analysis in macrophages revealed a significant decrease in oxidative phosphorylation and coupling efficiency after nanogel exposure, accompanied by increased proton leakage. Despite these metabolic disruptions, glycolysis remained unaffected. The Poloxamer matrix appears to be responsible for these effects, independent of the presence of bile acids or Tyloxapol. This study highlights the potential of bile acid-enriched nanogels in drug delivery, particularly their biocompatibility and injectability while acknowledging challenges related to mitochondrial dysfunction in immune cells. These findings suggest that thermoresponsive bile acid and Tyloxapol nanogels have the potential to be safe and effective drug delivery vehicles for inner ear applications.

本研究介绍了由苯去氧胆酸和泰乐菌素组成的新型热致伸缩性纳米凝胶，可用于内耳给药。这种纳米凝胶具有非牛顿、剪切稀化流体特性，并能在体温下快速凝胶化。对听觉细胞系和巨噬细胞系进行了生物相容性研究。暴露 24 小时后，纳米凝胶对听觉细胞的细胞活力、糖酵解和线粒体呼吸的影响极小。然而，对巨噬细胞线粒体功能的分析表明，接触纳米凝胶后氧化磷酸化和耦合效率显著下降，同时质子泄漏增加。尽管出现了这些代谢紊乱，但糖酵解仍未受到影响。Poloxamer基质似乎是造成这些影响的原因，而与胆汁酸或泰乐菌素的存在无关。这项研究强调了富含胆汁酸的纳米凝胶在给药方面的潜力，特别是其生物相容性和可注射性，同时也承认了与免疫细胞线粒体功能障碍有关的挑战。这些研究结果表明，热致伸缩性胆汁酸和泰乐菌素纳米凝胶有可能成为安全有效的内耳给药载体。

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引用次数: 0

Chitosan/siRNA complex in mimetic high-density lipoproteins as specific/hybrid transfection technology for SR-B1 expressing cancer cells 壳聚糖/siRNA 复合物在模拟高密度脂蛋白中作为 SR-B1 表达癌细胞的特异性/杂交转染技术

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-11 DOI: 10.1016/j.jddst.2024.106274

Liliana Aranda-Lara , Maydelid Trujillo-Nolasco , Clere M. López-Marmolejo , Karla Cárdenas-Rodríguez , Vanesa O. Gómez-Pulido , Enrique Morales-Avila , Blanca Ocampo-García , Nallely P. Jiménez-Mancilla , José A. Estrada , Gloria Otero , Keila Isaac-Olivé

The development of nanotechnology-based siRNA-delivery systems offers an avenue to improve gene therapy and combined therapies. The radiopharmaceutical ²²⁵Ac-DOTA-Bombesin is internalized in cells with high expression of gastrin release peptide receptor (GRPR), such as breast cancer cells (T47D). α-radiation emitted by ²²⁵Ac is lethal to the cell due to a high rate of induced double-strand breaks (DSBs). siRNA-RAD51 inhibits RAD51 protein synthesis, preventing the repair of DSBs in DNA. If gene silencing of RAD51 and ²²⁵Ac converge in T47D cells, a combined gene/radiation therapy is achieved, since RAD51 silencing by siRNA-RAD51 will prevent cellular repair of ²²⁵Ac-induced DSBs. However, siRNA requires an efficient delivery system. In this work, a hybrid technology based on mimetic high-density lipoprotein (mHDL) was developed for siRNA-RAD51 transport. Chitosan/siRNA (CS/siRNA) complexes were prepared and were coated with lipids and Apo-A1 mimetic peptide (D-4F), to assemble mHDL(CS/siRNA). The presence of D-4F peptide targeted the nanosystem to scavenger receptor B1 (SR-B1), which is overexpressed in cancer cells (e.g., T47D cancer cell line). A CS/siRNA-Cy3 complex, with similar chemical properties to CS/siRNA-RAD51, was used for chemical characterization and evaluation of in vitro transfection. The results showed that mHDL(CS/siRNA-Cy3) is stable in serum, protects siRNA from RNases, and transfects by specific recognition of SR-B1. Pretreatment with mHDL(CS/siRNA-RAD51) resulted in gene silencing and, in combination with ²²⁵Ac-DOTA-Bombesin, significantly reduced the viability of T47D cells. The mHDL(CS/siRNA-RAD51) nanosystem is suitable for siRNA-specific transfection, being an efficient and specific/hybrid technology to sensitize cancer cells overexpressing SR-B1.

基于纳米技术的 siRNA 给药系统的开发为改进基因疗法和联合疗法提供了一条途径。放射性药物 225Ac-DOTA-Bombesin 能被胃泌素释放肽受体（GRPR）高表达的细胞（如乳腺癌细胞（T47D））内化。siRNA-RAD51 可抑制 RAD51 蛋白的合成，阻止 DNA 中 DSB 的修复。如果 RAD51 基因沉默和 225Ac 基因沉默在 T47D 细胞中汇合，就能实现基因/辐射联合疗法，因为 siRNA-RAD51 沉默 RAD51 会阻止细胞修复 225Ac 诱导的 DSB。然而，siRNA 需要高效的递送系统。本研究开发了一种基于仿高密度脂蛋白（mHDL）的混合技术，用于 siRNA-RAD51 的转运。研究人员制备了壳聚糖/siRNA（CS/siRNA）复合物，并用脂质和载脂蛋白-A1模拟肽（D-4F）包被，组装成 mHDL(CS/siRNA)。D-4F 肽的存在使纳米系统靶向清道夫受体 B1（SR-B1），该受体在癌细胞（如 T47D 癌细胞系）中过度表达。CS/siRNA-Cy3复合物与CS/siRNA-RAD51具有相似的化学特性，被用于化学特征鉴定和体外转染评估。结果表明，mHDL(CS/siRNA-Cy3)在血清中稳定，能保护 siRNA 免受 RN 酶的侵蚀，并能通过特异性识别 SR-B1 进行转染。用 mHDL(CS/siRNA-RAD51)预处理可导致基因沉默，与 225Ac-DOTA-Bombesin 联合使用可显著降低 T47D 细胞的活力。mHDL(CS/siRNA-RAD51)纳米系统适用于siRNA特异性转染，是一种高效、特异性/混合技术，可敏化过表达SR-B1的癌细胞。

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引用次数: 0

Silver loaded functionalized calix [4]arene nanofibers and evaluation in burn wound healing 负载银的功能化钙[4]烯纳米纤维及其在烧伤创面愈合中的应用评估

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-11 DOI: 10.1016/j.jddst.2024.106268

Esra Maltas Cagil , Fatih Ozcan , Cengizhan Ceylan , Seyma Tetik Rama , Kubra Yilmaz , Zeliha Esin Celik , Abdullah Sivrikaya , Harun Yonar

Burn treatments with gene therapy and healing factors requires highly cost techniques. Instead, topical formulations including plant extract or pharmaceuticals are offered for wound-healing effect. However, these have low water solubility and cannot uptake into cells sufficiently. To overcome disadvantages, new effective treatment approaches should have been accessible. This study aimed to develop nanofiber-based wound coverings using four different Ag(I)-calixarene derivatives. Their nanofibers were produced by the electrospin method, and evaluated in vivo in rats with a second-degree burn model. Biochemical analysis has been maintained to exmine the effects of formulations on such as growth factors and some cytokines that are effective in wound healing process. In addition, histopathological analyzes has been performed to evaluate the presence and density of granulation tissue, inflammation, epithelial thickness and fibrosis. All data were compared with a commercial topical, silver sulfadiazine, whose usage is limited due to various disadvantages in the treatment processes of burn wounds. In this study, four different calixarene derivatives were synthesized their nanofibers were produced by the electrospin method, and their effectiveness was evaluated in vivo in rats with a second-degree burn model. Then, various biochemical and histopathological analyses were done to elucidate the possible wound-healing mechanism. When considering both pathological and biochemical data, the nanofibers of CLX-SAMD-Ag (5,11,17,23‐tetra‐tert‐butyl‐25,27‐bis(Sulfadiazine)‐26,28‐propylcalix (Xie and Unser, 2013) [4]arene - Ag) and CLX-MORF- Ag (5,11,17,23‐tetra‐tert‐butyl‐25,27‐bis(3-Morpholinopropil)‐26,28‐dihydroxycalix (Xie and Unser, 2013) [4]arene-Ag) were found to be more effective than silver sulfadiazine -silver content application, also known as traditional burn treatment for wound healing.

使用基因疗法和愈合因子治疗烧伤需要高成本技术。相反，外用制剂（包括植物提取物或药物）可以达到愈合伤口的效果。然而，这些药物的水溶性较低，不能充分吸收到细胞中。为了克服这些弊端，我们需要新的有效治疗方法。本研究旨在利用四种不同的银(I)-霞石衍生物开发基于纳米纤维的伤口覆盖物。这些纳米纤维通过电纺丝方法制成，并在二度烧伤模型大鼠体内进行了评估。通过生化分析，确定了制剂对伤口愈合过程中有效的生长因子和某些细胞因子的影响。此外，还进行了组织病理学分析，以评估肉芽组织的存在和密度、炎症、上皮厚度和纤维化。所有数据都与商业外用药磺胺嘧啶银进行了比较，由于磺胺嘧啶银在烧伤伤口治疗过程中的各种缺点，其使用受到了限制。本研究合成了四种不同的钙烯烃衍生物，并通过电纺丝法制成纳米纤维，在二度烧伤模型大鼠体内评估了其有效性。然后，进行了各种生化和组织病理学分析，以阐明可能的伤口愈合机制。考虑到病理和生化数据，CLX-SAMD-Ag（5,11,17,23-四叔丁基-25,27-双（磺胺嘧啶）-26,28-丙基萼片（Xie 和 Unser，2013 年）[4]炔-Ag）和 CLX-MORF- Ag（5,11,17、23-四叔丁基-25,27-双（3-吗啉丙基）-26,28-二羟基萼片（Xie 和 Unser，2013 年）[4]炔-银）比磺胺嘧啶银-银含量应用更有效，后者也被称为传统烧伤愈合疗法。

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引用次数: 0

Curcumin-loaded pickering emulsions based on soy protein isolate aggregates enhance diabetic wound healing 基于大豆分离蛋白聚合体的姜黄素腌制乳剂可促进糖尿病伤口愈合

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-11 DOI: 10.1016/j.jddst.2024.106279

Soroush Behjati Hosseini , Payam Arghavani , Jun Hong , Hamid Reza Rahimi , Saeed Azad-Armaki , Reza Yousefi , Ali Akbar Moosavi-Movahedi

Wound healing in diabetic patients is more complex and prolonged in comparison to nondiabetic persons, and dealing with this problem has attracted considerable attention from researchers. According to its anti-inflammatory and anti-infective properties, Curcumin has a valued place in therapeutics, including wound healing. Still, its low stability and poor bioavailability are significant barriers to using its desirable properties. Hence, various biocompatible and biodegradable delivery systems have been developed to address this issue. In this study, Pickering emulsion (PE) prepared from soybean oil containing curcumin and modified SPI solution at 85 °C at pH 2.0 with 130 mM NaCl for different durations were used as a delivery system for curcumin. Changes in SPI properties were analyzed using fluorescence spectroscopy, Fourier transform infrared spectroscopy, and tensiometry methods. The prepared PEs were studied using microscopic techniques. Curcumin loading efficiency by PE was measured by UV–visible spectroscopy, and the impact of curcumin-loaded PE on wound healing was tested in diabetic rats. Spectroscopic studies and microscopy images revealed SPI amyloid-like aggregates suitable for stabilizing oil-in-water PEs. Tensiometry and creaming stability studies indicated that at least 6 h of heating (HSPI₆) is necessary for optimal stability. Curcumin encapsulation efficiency was 95.7 ± 2.1 %. Curcumin-loaded PE-HSPI₆ increased the healing rate of diabetic wounds in male Wistar rats by 1.46-fold. This study presents an approach for using biocompatible and biodegradable PEs to deliver hydrophobic compounds like curcumin for accelerating diabetic wound healing.

与非糖尿病患者相比，糖尿病患者的伤口愈合更为复杂，时间也更长。姜黄素具有抗炎和抗感染的特性，因此在伤口愈合等治疗领域具有重要地位。然而，姜黄素的低稳定性和低生物利用度是利用其理想特性的重大障碍。因此，人们开发了各种生物相容性和可生物降解的给药系统来解决这一问题。在本研究中，使用含有姜黄素的大豆油制备的皮克林乳液（PE）和改良的 SPI 溶液作为姜黄素的给药系统，SPI 溶液在 85 ℃、pH 值为 2.0、130 mM NaCl 的条件下持续不同的时间。使用荧光光谱法、傅立叶变换红外光谱法和张力测定法分析了 SPI 性能的变化。使用显微技术对制备的 PE 进行了研究。利用紫外可见光谱法测量了姜黄素在 PE 中的负载效率，并测试了负载姜黄素的 PE 对糖尿病大鼠伤口愈合的影响。光谱研究和显微图像显示，SPI 淀粉样聚集体适用于稳定水包油聚乙烯。张力测定法和起皱稳定性研究表明，要达到最佳稳定性，至少需要加热 6 小时（HSPI6）。姜黄素的封装效率为 95.7 ± 2.1 %。负载姜黄素的 PE-HSPI6 使雄性 Wistar 大鼠糖尿病伤口的愈合率提高了 1.46 倍。本研究提出了一种使用生物相容性和生物可降解聚乙烯来递送疏水性化合物（如姜黄素）以加速糖尿病伤口愈合的方法。

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引用次数: 0

Enhancing doxorubicin efficacy with vitamin E-TPGS nanosystems in cancer therapy 在癌症治疗中利用维生素 E-TPGS 纳米系统提高多柔比星疗效

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-11 DOI: 10.1016/j.jddst.2024.106286

Mohd Shoab Ali , Amirhossein Sahebkar , Garima Gupta , Zia Ul-Sabah , Shadma Wahab , Prashant Kesharwani

Doxorubicin, a commonly used chemotherapeutic medication, poses substantial hurdles due to the development of resistance in tumor cells. Resistance mechanisms include up-regulation of efflux pumps such as P-gp, improved drug metabolism, and evasion of apoptosis. P-gp is an important membrane-bound efflux pump involved in multidrug resistance in cancer cells. It decreases the intracellular concentration and efficiency of many medicines, including chemotherapeutics like doxorubicin, by actively moving them out of cells. The MDR1 gene encodes this protein, which is highly expressed in a variety of organs, including the liver, kidney, and intestines, as well as many cancers. Inhibiting P-gp activity is a critical method for combating drug resistance and improving chemotherapeutic effectiveness. Due to this, novel approaches are being investigated, such as adding TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate) to therapeutic formulations, which can block efflux pumps and improve drug solubility and bioavailability. TPGS is a water-soluble vitamin E derivative that functions well as an enhancer of drug delivery and because of its amphiphilic nature, it can function as a surfactant which enhances the solubility and bioavailability of poorly soluble medications. Another well-known property of TPGS is its capacity to inhibit P-glycoprotein (P-gp), which allows cancer cells to withstand drugs and overcome drug efflux. Because of this, TPGS is a useful ingredient in the formulation of chemotherapy drugs like doxorubicin by improving their therapeutic effectiveness. The potential of TPGS in overcoming the resistance of doxorubicin was discussed in this review article.

多柔比星是一种常用的化疗药物，但由于肿瘤细胞产生抗药性而造成了巨大的障碍。抗药性机制包括 P-gp 等外排泵的上调、药物代谢的改善以及凋亡的逃避。P-gp 是一种重要的膜结合外排泵，参与癌细胞的多药耐药性。它能主动将许多药物（包括多柔比星等化疗药物）移出细胞，从而降低这些药物的细胞内浓度和效率。MDR1 基因编码这种蛋白质，它在肝脏、肾脏、肠道等多种器官以及许多癌症中都高度表达。抑制 P-gp 活性是对抗耐药性和提高化疗效果的关键方法。因此，人们正在研究新的方法，例如在治疗配方中添加 TPGS（d-α-生育酚聚乙二醇 1000琥珀酸酯），它可以阻断外排泵，提高药物的溶解度和生物利用度。TPGS 是一种水溶性维生素 E 衍生物，具有良好的给药增强功能，由于其两亲性，它可以作为一种表面活性剂，提高溶解性差的药物的溶解度和生物利用度。TPGS 的另一个众所周知的特性是它能够抑制 P-糖蛋白（P-gp），从而使癌细胞能够承受药物并克服药物外流。正因为如此，TPGS 可提高多柔比星等化疗药物的疗效，是配制此类药物的有效成分。本综述文章讨论了 TPGS 在克服多柔比星耐药性方面的潜力。

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引用次数: 0

Design of an oral formulation combining PVA nanofibers and PEGylated liposomes for enhanced drug delivery 设计一种结合 PVA 纳米纤维和 PEG 化脂质体的口服制剂，以增强给药效果

IF 4.5 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology

Pub Date : 2024-10-11 DOI: 10.1016/j.jddst.2024.106285

Momona Iwai , Eriko Yamazoe , Takaaki Ito , Kouji Hara , Kohei Tahara

Modifying the surface properties of nanoparticles is crucial for enhancing the oral absorption of encapsulated drugs. Although both mucoadhesion and mucus permeability are essential properties for improving oral absorption, their opposing characteristics render their combination in a single formulation challenging. The present study aimed to integrate both strategies and design a novel oral formulation by creating nanofibers from a mucoadhesive polymer solution containing approximately 100 nm PEGylated liposomes. First, we evaluated the physicochemical properties of PEGylated liposomes released from nanofibers made of sodium carboxymethylcellulose (CMC-Na) and polyvinyl alcohol (PVA), as well as from PVA alone nanofibers. Liposomes released from CMC-Na/PVA nanofibers had a particle size of 533.9 ± 85.0 nm, showing aggregation, while those from PVA nanofibers maintained a particle size without aggregation (142.8 ± 7.31 nm). To increase the liposome content in PVA nanofibers, we used hydroxypropyl-β-cyclodextrin (HPβCD) as a cryoprotectant, converting the suspension to powder and increasing liposome content by approximately 30-fold. PVA nanofibers increasing liposome content had a fiber diameter of 355.5 ± 77.1 nm, and liposomes released from nanofibers retained their morphology. We then used the flow-through method to evaluate the formulation's adhesive properties, and our findings confirmed its better mucosal adhesion and reduced excretion by mucus clearance (about 1/10) compared to a liposome suspension. Subsequent application to rat intestinal tissue showed that the mucus partially dissolved the nanofibers, allowing PEGylated liposomes to penetrate the mucus layer. Oral administration to rats showed improved gastrointestinal retention, thereby confirming that this novel oral formulation may improve drug oral absorption.

改变纳米颗粒的表面特性对于提高封装药物的口服吸收至关重要。虽然粘液粘附性和粘液渗透性都是促进口服吸收的基本特性，但由于两者的特性截然相反，因此在单一配方中将两者结合起来具有挑战性。本研究旨在整合这两种策略，设计出一种新型口服制剂，即从含有约 100 纳米 PEG 化脂质体的粘液黏附性聚合物溶液中生成纳米纤维。首先，我们评估了由羧甲基纤维素钠（CMC-Na）和聚乙烯醇（PVA）制成的纳米纤维释放的 PEG 化脂质体以及仅由 PVA 制成的纳米纤维释放的 PEG 化脂质体的理化性质。从 CMC-Na/PVA 纳米纤维中释放的脂质体的粒径为 533.9 ± 85.0 nm，出现了聚集现象，而从 PVA 纳米纤维中释放的脂质体的粒径保持不变（142.8 ± 7.31 nm）。为了增加 PVA 纳米纤维中的脂质体含量，我们使用羟丙基-β-环糊精（HPβCD）作为低温保护剂，将悬浮液转化为粉末，使脂质体含量增加了约 30 倍。增加脂质体含量的 PVA 纳米纤维的直径为 355.5 ± 77.1 nm，从纳米纤维中释放的脂质体保持了其形态。与脂质体悬浮液相比，我们的研究结果证实该制剂具有更好的粘膜粘附性，并减少了通过粘液清除的排泄量（约为1/10）。随后在大鼠肠道组织中的应用表明，粘液部分溶解了纳米纤维，使聚乙二醇脂质体得以穿透粘液层。对大鼠的口服给药显示，胃肠道保留率有所提高，从而证实这种新型口服制剂可改善药物的口服吸收。

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引用次数: 0