International Journal of Pharmaceutics: X最新文献_第2页

Multifunctional poloxamer-based thermo-responsive hydrogel loaded with human lactoferricin niosomes: In vitro study on anti-bacterial activity, accelerate wound healing, and anti-inflammation 以聚氧乙烯醚为基础的多功能热响应水凝胶载入人乳铁蛋白纳米体：关于抗菌活性、加速伤口愈合和抗炎的体外研究

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-10-11 DOI: 10.1016/j.ijpx.2024.100291

Sirikwan Sangboonruang , Natthawat Semakul , Kiattikhun Manokruang , Nuttawut Khammata , Kanyaluck Jantakee , Katanchalee Mai-Ngam , Satrawut Charoenla , Phadungkiat Khamnoi , Kanokwan Saengsawang , Usanee Wattananandkul , Sorasak Intorasoot , Khajornsak Tragoolpua

Chronic wound infections are attributed to delayed tissue repair, which remains a major clinical challenge in long-term health care. Particularly, infections with antibiotic resistance have more serious effects on health, often resulting in unsuccessful treatments. Thus, antimicrobial peptide (AMP)-based therapy holds promise as a potential therapeutic approach to overcoming drug resistance. Conventional wound dressing is a passive strategy for wound care that is not capable of eradicating pathogens and promoting tissue repair. In this study, we aim to construct an advanced wound dressing; a thermo-responsive hydrogel incorporated with lactoferricin (Lfcin) niosome (Lfcin-Nio/hydrogel) for bacterial pathogen treatment. The Lfcin-loaded niosome (Lfcin-Nio) has a particle size of 396.91 ± 20.96 nm, 0.38 ± 0.01 of PdI, −10.5 ± 0.3 mV of ζ potential, and 72.30 ± 7.05 % Lfcin entrapment efficiency. Lfcin-Nio exhibited broad antibacterial activity on both drug-susceptible and drug-resistant strains, and also on bacteria residing in the biofilm matrix. The Lfcin-Nio/hydrogel was fabricated from 0.5 % w/v poloxamer 188–20 % w/v poloxamer 407, and supplemented with Lfcin-Nio and epidermal growth factor (EGF). The physical properties of Lfcin-Nio/hydrogels showed elasticity, swelling ability, and strong injectability with responsiveness to 33–37 °C temperatures. The biological properties of Lfcin-Nio/hydrogels exhibited a bactericidal effect against drug-resistant strains of S. aureus and P. aeruginosa, and showed less toxicity to the human skin fibroblast. It also promoted the healing of scratches by 55 % within 6 h, compared to the wound closure rate of 20 % in the cell control. The inflammatory response of the Lfcin-Nio/hydrogel-treated cells was reduced via suppression of IL-1β and COX-2 mRNA expressions. From this study, Lfcin-Nio/hydrogels can be suggested as a modern wound dressing that possesses multifunctional and beneficial properties for the management of chronic wound infections.

慢性伤口感染是由于组织修复延迟造成的，这仍然是长期医疗保健的一大临床挑战。尤其是具有抗生素耐药性的感染对健康的影响更为严重，往往导致治疗失败。因此，基于抗菌肽（AMP）的疗法有望成为克服耐药性的一种潜在治疗方法。传统的伤口敷料是一种被动的伤口护理策略，无法根除病原体和促进组织修复。在本研究中，我们旨在构建一种先进的伤口敷料；一种含有乳铁蛋白（Lfcin）niosome（Lfcin-Nio/hydrogel）的热响应水凝胶，用于治疗细菌病原体。Lfcin-loaded niosome（Lfcin-Nio）的粒径为 396.91 ± 20.96 nm，PdI 为 0.38 ± 0.01，ζ电位为 -10.5 ± 0.3 mV，Lfcin 的夹持效率为 72.30 ± 7.05 %。Lfcin-Nio 对药物敏感菌株和耐药菌株以及生物膜基质中的细菌都具有广泛的抗菌活性。Lfcin-Nio/hydrogel 由 0.5 % w/v poloxamer 188-20 % w/v poloxamer 407 制成，并添加了 Lfcin-Nio 和表皮生长因子（EGF）。Lfcin-Nio/水凝胶的物理性质显示出弹性、溶胀能力和较强的注射性，对 33-37 °C 的温度反应灵敏。Lfcin-Nio/hydrogels 的生物特性表现出对金黄色葡萄球菌和绿脓杆菌耐药菌株的杀菌作用，对人体皮肤成纤维细胞的毒性较低。它还能促进划痕在 6 小时内愈合 55%，而细胞对照组的伤口闭合率仅为 20%。通过抑制 IL-1β 和 COX-2 mRNA 的表达，Lfcin-Nio/水凝胶处理细胞的炎症反应有所减轻。从这项研究中可以看出，Lfcin-Nio/水凝胶是一种现代伤口敷料，具有治疗慢性伤口感染的多功能和有益特性。

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引用次数: 0

Study on the preparation of stabilizer-free silymarin nanocrystals and its oral absorption mechanisms 无稳定剂水飞蓟素纳米晶体的制备及其口服吸收机制研究

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-10-10 DOI: 10.1016/j.ijpx.2024.100292

Liangxing Tu , Ping Han , Yongbing Sun , Yi Jin , Kaili Hu , Meng Cheng , Yisen Shao , Jianfang Feng , Fangying Yuan

Many researchers have studied the oral absorption mechanisms yet, however, considering stabilizers often participate in the absorption process of nanocrystals, these known mechanisms may be incorrect. Hence in this study, we aimed to explore the correct absorption mechanism of nanocrystals by performing related studies on stabilizer-free nanocrystals. We firstly prepared stabilizer-free silymarin nanocrystals by high-pressure homogenization, and then performed absorption-related studies, such as solubility, dissolution rate, pharmacokinetic study, cellular uptake and intracellular transport. Results showed the stabilizer-free silymarin nanocrystals had an average particle size of (450.2 ± 4.46) nm, with PDI of 0.280 ± 0.021 and Zeta potential of −26.9 ± 2.4 mV. The conversion of silymarin crude drug to stabilizer-free silymarin nanocrystals increased the compound's solubility by 1.41 times, with a dissolution rate of 92.2 % in water within 30 min compared to 38.5 % for crude drugs. Pharmacokinetic studies showed the oral bioavailability of stabilizer-free silymarin nanocrystals was found to be 1.48 times greater than that of the crude drugs. The cell experimentation results demonstrated that the stabilizer-silymarin nanocrystals can improve uptake but have poor transmembrane transport properties. Most researchers believe that nanocrystals can enhance transmembrane transport of drugs via an endocytosis-mediated pathway. In fact, nanocrystals are indeed endocytosed more by the cells, but this transport pathway is poor because the cells lack the intracellular transport pathway to transport nanocrystals from the AP side to the BP side. Therefore, we believe that the intracellular transport of nanocrystals can be enhanced by modifications and other carriers if needed to improve nanocrystals' ability to promote oral absorption.

然而，考虑到稳定剂通常会参与纳米晶体的吸收过程，这些已知机制可能并不正确。因此，本研究旨在通过对不含稳定剂的纳米晶体进行相关研究，探索纳米晶体的正确吸收机制。我们首先通过高压均质法制备了不含稳定剂的水飞蓟素纳米晶体，然后进行了吸收相关研究，如溶解度、溶出率、药代动力学研究、细胞摄取和细胞内转运等。结果表明，不含稳定剂的水飞蓟素纳米晶体的平均粒径为（450.2 ± 4.46）nm，PDI为0.280 ± 0.021，Zeta电位为-26.9 ± 2.4 mV。将水飞蓟素原药转化为不含稳定剂的水飞蓟素纳米晶体后，该化合物的溶解度提高了 1.41 倍，30 分钟内在水中的溶解度为 92.2%，而原药的溶解度仅为 38.5%。药代动力学研究表明，不含稳定剂的水飞蓟素纳米晶体的口服生物利用度是原药的 1.48 倍。细胞实验结果表明，含稳定剂的水飞蓟素纳米晶体能提高吸收率，但跨膜转运性能较差。大多数研究人员认为，纳米晶体可通过内吞途径提高药物的跨膜转运。事实上，纳米晶体确实更多地被细胞内吞，但这种转运途径很差，因为细胞缺乏将纳米晶体从 AP 侧转运到 BP 侧的胞内转运途径。因此，我们认为，如果需要，可以通过改性和其他载体来增强纳米晶体的胞内转运，从而提高纳米晶体促进口服吸收的能力。

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引用次数: 0

Investigating the effect of whey and casein proteins on drug solubility from a paediatric drug absorption perspective 从儿科药物吸收角度研究乳清蛋白和酪蛋白对药物溶解度的影响

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-10-09 DOI: 10.1016/j.ijpx.2024.100290

Matthias Van der Veken , Joachim Brouwers , Neil Parrott , Patrick Augustijns , Cordula Stillhart

Considering the predominantly milk-based diet of neonates and infants and their immature gastrointestinal digestion, milk proteins may affect drug behaviour and absorption in this population. Using in vitro models, this study investigated the impact of the representative milk proteins, whey and casein, on the solubility and permeation of the lipophilic model drugs spironolactone, clopidogrel and ritonavir. Drug solubility experiments revealed that the presence of milk proteins increased drug solubility. Next, permeation studies demonstrated that the same milk proteins reduced drug permeation across an artificial membrane. These results highlight the importance of the solubility-permeability interplay and indicate the effect of these proteins may be considered during (paediatric) drug development. Lastly, the findings underscore the importance of considering milk protein-drug interactions to optimize drug delivery strategies during (paediatric) drug development and especially for the youngest and most vulnerable part of this population.

考虑到新生儿和婴儿的饮食主要以牛奶为主，而且他们的胃肠道消化功能尚未成熟，牛奶蛋白可能会影响药物在这一人群中的行为和吸收。本研究利用体外模型，研究了代表性牛奶蛋白（乳清蛋白和酪蛋白）对亲脂性模型药物螺内酯、氯吡格雷和利托那韦的溶解度和渗透性的影响。药物溶解度实验表明，牛奶蛋白的存在增加了药物的溶解度。接下来的渗透研究表明，同样的牛奶蛋白降低了药物在人工膜上的渗透。这些结果突显了溶解度和渗透性相互作用的重要性，并表明在（儿科）药物开发过程中可以考虑这些蛋白质的影响。最后，研究结果强调了在开发（儿科）药物过程中考虑牛奶蛋白与药物相互作用以优化给药策略的重要性，尤其是对这一人群中最年轻和最脆弱的部分。

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引用次数: 0

Antiaging synergistic effect in noninvasive transdermal delivery of peptide loaded liposomes by low energy/frequency radiofrequency 低能量/高频射频非侵入性透皮给药多肽脂质体的抗衰老协同效应

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-10-05 DOI: 10.1016/j.ijpx.2024.100289

Nanxi Xiang , Zeting Huang , Chunqiao Zhang , Jiahong Huang , Zhenyuan Wang , Jichuan Zhang , Chengyu Wu , Weihua Peng , Jiaheng Zhang

Low energy/frequency radiofrequency (LRF) combined with the transdermal delivery of liposome (L) encapsulated antiaging peptides technology is a remarkable, newly developed physical noninvasive transdermal penetration technique; it is considered a highly efficient, comprehensive and safe technology. In this study, our objective was to evaluate the physical and chemical mechanisms underlying the efficacy of this innovative technique involving a combination of LRF and L, termed LLRF, that exerts a synergistic anti-aging effect on human skin, via an animal experiment. Physical and chemical analyses indicated that a relatively stable liposome with a uniform nano-size, which was formed, possessed good transdermal permeability that was 2.74 folds higher than that of the free peptide (F). LLRF exhibited a higher transdermal permeation performance that was of 3.65 folds higher than that of the free one, which was substantiated via confocal laser scanning fluorescence microscopy. The mouse UVB photoaging model trial confirmed that the LLRF technology exerted a significant synergistic effect compared to liposome technology, or free peptide, by downregulating inflammatory factors (IL-6, TNF-α), inhibiting the mRNA and protein expression of matrix metalloproteinases (MMP1, MMP3), promoting the mRNA and protein expression of related collagens (Procollagen, Col1α1 and Col3α1), and repairing the stratum corneum barrier function, as evidenced by trans-epidermal water loss (TEWL), skin cuticle hydration (SCH), and decreased expression of β-gal, an aging marker. These findings indicated that photoaging skin can be effectively and comprehensively rejuvenated, and that even photodamage can be reversed, thereby restoring the original physiological characteristics of healthy skin. Clinical tests have confirmed that although liposome technology is an effective antiaging method which helps exert tightening and anti-wrinkle effects on human skin, LLRF is an even more effective anti-aging technique. This study reveals a highly effective technique involving a combination physical and chemical therapy that may be utilized for antiaging purposes as well as repairing lightly damaged skin, and can be made readily available in the future.

低能/高频射频（LRF）结合脂质体（L）包裹抗衰老肽透皮给药技术是一种新开发的非侵入性物理透皮渗透技术，被认为是一种高效、全面和安全的技术。在本研究中，我们的目标是通过动物实验来评估这种创新技术的物理和化学机制，包括 LRF 和 L（称为 LLRF）的组合，它能对人体皮肤产生协同抗衰老效果。理化分析表明，形成的相对稳定的纳米级脂质体具有良好的透皮渗透性，比游离肽（F）的透皮渗透性高 2.74 倍。LLRF 的透皮渗透性比游离肽高出 3.65 倍，这一点已通过共聚焦激光扫描荧光显微镜得到证实。小鼠 UVB 光老化模型试验证实，与脂质体技术或游离肽相比，LLRF 技术具有显著的协同效应，能下调炎症因子（IL-6、TNF-α），抑制基质金属蛋白酶（MMP1、MMP3），促进相关胶原蛋白（Procollagen、Col1α1 和 Col3α1）的 mRNA 和蛋白表达，修复角质层屏障功能，具体表现为经表皮失水（TEWL）、皮肤角质层水合（SCH）和衰老标志物 β-gal 的表达减少。这些研究结果表明，光老化皮肤可以有效、全面地恢复青春活力，甚至可以逆转光损伤，从而恢复健康皮肤原有的生理特征。临床试验证实，虽然脂质体技术是一种有效的抗衰老方法，能帮助人体皮肤发挥紧致和抗皱效果，但 LLRF 是一种更有效的抗衰老技术。这项研究揭示了一种结合物理和化学疗法的高效技术，可用于抗衰老和修复轻度受损的皮肤，并可在未来随时投入使用。

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引用次数: 0

Autoencoder-based inverse design and surrogate-based optimization of an integrated wet granulation manufacturing process 基于自动编码器的湿法造粒集成制造工艺的逆向设计和代用优化

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-09-26 DOI: 10.1016/j.ijpx.2024.100287

Ashley Dan, Rohit Ramachandran

In pharmaceutical manufacturing, integrating model-based design and optimization can be beneficial for accelerating process development. This study explores the utilization of Machine Learning (ML) techniques as a surrogate model for the optimization of a three-unit wet-granulation based flowsheet model for solid dosage form manufacturing. First, a reduced representation of a wet granulation flowsheet model is developed, incorporating a granulation and milling process, along with a novel dissolution model that accounts for the effect of particle size, porosity, and microstructure on dissolution rate. Two optimization approaches are compared, including an autoencoder-based inverse design and a surrogate-based forward optimization. Both methods address the bi-objective problem of maximizing dissolution time and product yield by identifying the optimal granulation and mill process parameters. For this case study, both approaches were effective and incurred a similar computational cost, averaging under 4 s. However, the autoencoder approach offers an advantage through dimensionality reduction, a feature not available in surrogate-based optimization. Dimensional reduction is particularly beneficial for complex process designs with numerous inputs and outputs. The lower dimensional representation helps improve process understanding through enhanced visualization of the process design space and facilitates feasibility studies involving multiple constraints. The autoencoder-based inverse design introduced in this work showcases an implementation of AI and ML in pharmaceutical process development, demonstrating the potential to enhance process efficiency and product quality in complex manufacturing scenarios.

在制药过程中，将基于模型的设计与优化结合起来有利于加速工艺开发。本研究探讨了如何利用机器学习（ML）技术作为代用模型，优化固体制剂生产中基于湿法制粒的三单元流程表模型。首先，开发了湿制粒流程表模型的简化表示法，其中包含制粒和研磨过程，以及考虑到粒度、孔隙率和微观结构对溶出率影响的新型溶出模型。比较了两种优化方法，包括基于自动编码器的逆向设计和基于代理的正向优化。这两种方法都通过确定最佳制粒和研磨工艺参数来解决溶解时间和产品产量最大化的双目标问题。然而，自动编码器方法通过降维提供了优势，这是基于代理的优化所不具备的功能。降维对于具有大量输入和输出的复杂流程设计尤为有利。低维表示法有助于通过增强工艺设计空间的可视化来提高对工艺的理解，并促进涉及多个约束条件的可行性研究。这项工作中介绍的基于自动编码器的逆向设计展示了人工智能和 ML 在制药工艺开发中的应用，证明了在复杂的生产场景中提高工艺效率和产品质量的潜力。

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引用次数: 0

Multifunctional Bi2S3-Au nanoclusters for fluorescence/infrared thermal imaging guided photothermal therapy 用于荧光/红外热成像引导光热疗法的多功能 Bi2S3-Au 纳米团簇

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-09-17 DOI: 10.1016/j.ijpx.2024.100286

Hongmei Sun , Yuyu Cao , Beibei Zhai , Xiaoshuang Zhao , Xuejun Zhang , Jiangtao Su

Nanotechnology has attracted extensive attention in the diagnosis and treatment of cancer. Therefore, the research aimed at developing new nanomaterials and exploring their applications in biomedicine has attracted more attention. In this study, Bi₂S₃-Au nanoclusters (Bi₂S₃-AuNCs) as fluorescence/infrared thermal imaging-guided photothermal therapy (PTT) was prepared for the first time. It was achieved in a facile and mild way by optimizing the amount of Bi³⁺ and Au³⁺ using bovine serum albumin (BSA) as reducer and stabilizer. The as-prepared Bi₂S₃-AuNCs with special morphology showed high stability, excellent biocompatibility and good photostability. Apart from these, it also can accumulate at tumor sites and exhibit considerable fluorescence/infrared thermal imaging-guided PTT. Bi₂S₃-AuNCs nanoparticles integrate imaging and therapeutic functions into an advanced application platform, which provides the possibility to build a novel nano-cancer diagnosis and treatment platform.

纳米技术在癌症诊断和治疗方面引起了广泛关注。因此，旨在开发新型纳米材料并探索其在生物医学中的应用的研究引起了更多关注。本研究首次制备了作为荧光/红外热成像引导的光热疗法（PTT）的 Bi2S3-Au 纳米团簇（Bi2S3-AuNCs）。该研究以牛血清白蛋白（BSA）作为还原剂和稳定剂，通过优化 Bi3+ 和 Au3+ 的用量，以简便、温和的方法实现了这一目标。制备出的具有特殊形貌的 Bi2S3-AuNCs 具有高稳定性、优异的生物相容性和良好的光稳定性。除此以外，它还能在肿瘤部位积聚，并在荧光/红外热成像引导下显示出可观的 PTT。Bi2S3-AuNCs 纳米粒子集成像和治疗功能于一体，是一种先进的应用平台，为构建新型纳米癌症诊断和治疗平台提供了可能。

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引用次数: 0

Tacrolimus: Physicochemical stability challenges, analytical methods, and new formulations 他克莫司理化稳定性挑战、分析方法和新制剂

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-09-15 DOI: 10.1016/j.ijpx.2024.100285

Sara Sajjadi , Ali Shayanfar , Farhad Kiafar , Mohammadreza Siahi-Shadbad

Tacrolimus, a potent immunosuppressant, is widely used in several formulations to treat organ rejection in transplant patients. However, its physicochemical stability poses significant challenges, including thermal instability, photostability issues, low solubility, and drug-excipient incompatibility. This review article focuses on the details of these challenges and discusses the analytical methods employed to study tacrolimus stability, such as thermal, spectroscopic, and chromatographic methods in different formulations. New formulations to enhance tacrolimus stability are explored, including lipid-based nanocarriers, polymers, and thin film freezing. Researchers and formulators can optimize tacrolimus formulations to improve efficacy and patient outcomes by understanding and addressing these stability challenges.

他克莫司是一种强效免疫抑制剂，被广泛应用于多种制剂中，用于治疗移植患者的器官排斥反应。然而，它的理化稳定性带来了巨大的挑战，包括热不稳定性、光稳定性问题、低溶解度以及药物与辅料不相容等。这篇综述文章重点介绍了这些挑战的细节，并讨论了研究他克莫司稳定性所采用的分析方法，如不同制剂中的热分析法、光谱法和色谱法。文章探讨了提高他克莫司稳定性的新配方，包括脂质纳米载体、聚合物和薄膜冷冻。研究人员和配方设计师可以通过了解和应对这些稳定性挑战来优化他克莫司配方，从而提高疗效和患者预后。

引用次数: 0

Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model 开发新型肌肉注射脂质体，用于美洛昔康的高级给药：骨科疼痛模型的制备、表征、体内药代动力学、药效学和疼痛评估

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-09-14 DOI: 10.1016/j.ijpx.2024.100284

Pierre A. Hanna , Hatim A. Al-Abbadi , Mohamed A. Hashem , Aziza E. Mostafa , Yasmina K. Mahmoud , Eman A. Ahmed , Ibrahim M. Hegab , Ibrahim E. Helal , Mahmoud F. Ahmed

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t_1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t_1/2 and AUC₀_–₂₄ and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

疼痛会产生多种生理和退行性并发症。本研究旨在将美洛昔康（MLX）配制成脂质体，以增加其溶解度，并以可控方式递送 MLX，从而克服其水溶性差和 t1/2 较短的问题。脂质体的制备方法是薄膜水合，然后进行超声处理。表征制剂特性的测试包括粒度、跨度、夹持效率、载药量、稳定性、差示扫描量热法（DSC）、傅立叶变换红外光谱法（FT-IR）、形态学、体外释放、释放动力学数学建模，以及在接受骨科手术的狗身上进行的体内疼痛模型试验，随后进行了体内药代动力学、药效学和疼痛评估研究，并与参考标准 Mobitil® 进行了比较。脂质体 MLX 的粒径约为 100 纳米，包埋效率为 82%，药物负载率为 4.62%。稳定性研究、DSC 和傅立叶变换红外光谱显示，脂质体具有很高的稳定性。与 Mobitil® 相比，该制剂的体外控释模式得到了改善，体内药代动力学行为也得到了增强，表现为更高的 t1/2、AUC0-24 和更低的 Cl/F。药效学研究和疼痛量表显示，脂质体 MLX 比 Mobitil® 能更好地控制术后疼痛。总之，在脂质体中加入 MLX 可提高其溶解度和稳定性，以及镇痛特性。

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引用次数: 0

Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery 用于递送 RNA 的脂质纳米粒子配方和制备的综合分析

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-09-10 DOI: 10.1016/j.ijpx.2024.100283

Md. Anamul Haque , Archana Shrestha , Constantinos M. Mikelis , George Mattheolabakis

Nucleic acid-based therapeutics are a common approach that is increasingly popular for a wide spectrum of diseases. Lipid nanoparticles (LNPs) are promising delivery carriers that provide RNA stability, with strong transfection efficiency, favorable and tailorable pharmacokinetics, limited toxicity, and established translatability. In this review article, we describe the lipid-based delivery systems, focusing on lipid nanoparticles, the need of their use, provide a comprehensive analysis of each component, and highlight the advantages and disadvantages of the existing manufacturing processes. We further summarize the ongoing and completed clinical trials utilizing LNPs, indicating important aspects/questions worth of investigation, and analyze the future perspectives of this significant and promising therapeutic approach.

基于核酸的疗法是一种常见的方法，在治疗各种疾病方面越来越受欢迎。脂质纳米颗粒（LNPs）是一种很有前景的递送载体，它具有 RNA 稳定性、转染效率高、药代动力学良好且可定制、毒性有限、可转化性强等特点。在这篇综述文章中，我们介绍了基于脂质的递送系统，重点是脂质纳米颗粒及其使用需求，全面分析了每种成分，并强调了现有生产工艺的优缺点。我们进一步总结了正在进行和已经完成的利用 LNPs 的临床试验，指出了值得研究的重要方面/问题，并分析了这种重要而有前景的治疗方法的未来前景。

引用次数: 0

A simple nanoplatform of thermo-sensitive liposomes and gold nanorods to treat bone metastasis through improved chemotherapy combined with photothermal therapy 一种简单的热敏脂质体和金纳米棒纳米平台，通过改进化疗结合光热疗法治疗骨转移瘤

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X

Pub Date : 2024-08-30 DOI: 10.1016/j.ijpx.2024.100282

Jia Gu , Lifan Jiang , Zhongping Chen , Jun Qi

Bone metastasis remains a clinical challenge and is still considered incurable. While nanoparticles-based drug delivery and photothermal therapy (PTT) show promise in treating subcutaneous solid tumor, their therapeutic outcome in treating bone metastasis is limited, due to the inaccessibility of bone metastatic site and the complexity of bone metastasis. Herein, we reported a simple nanoplatform composed of thermo-sensitive liposomes (TSL) and gold nanorods (GNR) to treat bone metastasis through improved chemotherapy combined with GNR-assisted PTT. Lipid combination of TSL was firstly tailored to regulate its stability under physiological condition as well as its sensitivity in responding to PTT-caused mild hyperthermia. The obtained TSL with loaded drug was then combined with GNR to form the nanoplatform through unsophisticated incubation. Cell experiments revealed that upon near-infrared (NIR) irradiation, the nanoplatform effectively inhibited the viability and migration ability of tumor cells through PTT, PTT-triggered thermo-sensitive drug release, and PTT-augmented sensitivity of tumor cells to drug. In a murine model of bone metastasis, the nanoplatform enabled effective delivery of loaded drug and GNR to bone metastatic site for rapid drug release upon local NIR irradiation. Through killing tumor cells and rebalancing the turnover of osteoclasts and osteoblasts, the nanoplatform largely preserved bone structure for pain relief and survival extension. Inspired by the simplicity of nanoplatform acquirement and treatment operation, the strategy of liposomes-based thermo-sensitive drug delivery in combination with GNR-assisted PTT is considered greatly promising in treating bone metastasis.

骨转移瘤仍是一项临床难题，目前仍被认为是不治之症。虽然基于纳米颗粒的给药和光热疗法（PTT）在治疗皮下实体瘤方面显示出前景，但由于骨转移部位的不可接近性和骨转移的复杂性，它们在治疗骨转移方面的疗效有限。在此，我们报道了一种由热敏脂质体（TSL）和金纳米棒（GNR）组成的简单纳米平台，通过改进化疗结合 GNR 辅助 PTT 治疗骨转移瘤。首先对 TSL 的脂质组合进行了定制，以调节其在生理条件下的稳定性以及对 PTT 引起的轻度高热反应的敏感性。然后将得到的载药 TSL 与 GNR 结合，通过简单的孵育形成纳米平台。细胞实验表明，在近红外（NIR）照射下，纳米平台通过PTT有效抑制了肿瘤细胞的活力和迁移能力，PTT触发的热敏药物释放，以及PTT增强的肿瘤细胞对药物的敏感性。在小鼠骨转移模型中，该纳米平台能将负载的药物和 GNR 有效地输送到骨转移部位，并在局部近红外照射时快速释放药物。通过杀死肿瘤细胞并重新平衡破骨细胞和成骨细胞的新陈代谢，纳米平台在很大程度上保护了骨结构，从而缓解了疼痛并延长了存活时间。受纳米平台获取和治疗操作简便的启发，基于脂质体的热敏给药策略结合 GNR 辅助 PTT 被认为在治疗骨转移瘤方面大有可为。

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引用次数: 0