AAPS PharmSciTech最新文献_第6页

Dosage Optimization Using Physiologically Based Pharmacokinetic Modeling for Pediatric Patients with Renal Impairment: A Case Study of Meropenem 使用基于生理的药代动力学模型优化儿科肾脏损害患者的剂量：以美罗培南为例

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-16 DOI: 10.1208/s12249-024-03026-y

Najia Rahim, Muhammad Sarfraz, Abubakar Bello, Syed Baqir Shyum Naqvi

The pharmacokinetics of renally eliminated antibiotics can be influenced by changes associated with renal function and development in a growing subject. Little is known about the effects of renal insufficiency on the pharmacokinetics of meropenem in pediatric subjects. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of meropenem for pediatric patients that can be used to optimize meropenem dosing in pediatric patients with renal impairment (RI). The PBPK model was developed using GastroPlus™ 9.9 based on clinical data obtained from the literature and then scaled to pediatric patients with RI for dose optimization of meropenem. The goodness of fit of the model was assessed by comparing the predicted values of AUC_0-t, AUC_0-α, and C_max with the observed data and the average fold errors (AFE). The AFE values for AUC_0-t, AUC_0-α, and C_max in the pediatric population were measured to be 1.60, 1.08, and 1.48, respectively. In addition, dose optimization was performed in virtual pediatric populations with varying degrees of RI and a dose reduction to 10 mg/kg and 7.5 mg/kg was recommended for moderate and severe RI, respectively. In all virtual pediatric populations with RI, the plasma concentration reached the recommended time above the minimum inhibitory concentration (MIC) at all optimized doses. The developed PBPK model for meropenem provides a quantitative tool to assess the impact of RI on the pharmacokinetics of meropenem in pediatric patients, which may be useful for optimizing the dosing regimen.

Graphical Abstract

肾脏消除抗生素的药代动力学可能受到与肾脏功能和发展相关的变化的影响。目前对肾功能不全对儿童美罗培南药代动力学的影响知之甚少。本研究的目的是建立一个基于生理的美罗培南儿科患者药代动力学（PBPK）模型，该模型可用于优化美罗培南在儿科肾损害（RI）患者中的剂量。基于文献中获得的临床数据，使用GastroPlus™9.9开发PBPK模型，然后扩展到患有RI的儿科患者中，以优化美罗培南的剂量。将AUC0-t、AUC0-α、Cmax预测值与实测数据及平均折差（AFE）进行比较，评价模型的拟合优度。儿童AUC0-t、AUC0-α和Cmax的AFE值分别为1.60、1.08和1.48。此外，在不同程度的RI的虚拟儿科人群中进行了剂量优化，中度和重度RI的剂量分别减少到10 mg/kg和7.5 mg/kg。在所有具有RI的虚拟儿科人群中，在所有优化剂量下，血浆浓度达到最低抑制浓度（MIC）以上的推荐时间。所建立的美罗培南PBPK模型为评估RI对儿科患者美罗培南药代动力学的影响提供了定量工具，这可能有助于优化给药方案。图形抽象

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引用次数: 0

A New and Safe Delivery of Sildenafil Citrate Co-Evaporate Loaded Emulgels for the Cure of Certain Male Sexual Dysfunctions 一种新的、安全的递送柠檬酸西地那非共蒸发乳剂治疗某些男性性功能障碍

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-16 DOI: 10.1208/s12249-024-03027-x

Shaaban K. Osman, Abobakr M. Yassin, Taher M. Yassin, Ahmed M. Mohammed, Ahmed M. Abdelsalam, Wael A. Mahdi, Sultan Alshehri, Mohamed A. El Hamd, Ahmed A. H. Abdellatif, Mohammed A. Amin, Emad A. Taha

The present work focuses on the production of sildenafil co-evaporates loaded emulgels as topical dosage forms for the treatment of premature ejaculation and erectile dysfunction. Topical administration of sildenafil citrate (SILD) co-evaporates is expected to improve the bioavailability profile of the drug and to avoid the severe side effects accompanying the traditional SILD dosage forms, especially for prohibited cardiovascular cases. Firstly, the solubility of SILD was improved via solid dispersion via co-evaporation technique using PEG-5KDa and PVP-K90 as hydrophilic carriers. The modified co-evaporates were characterized by DSC, XRD, and solubility studies. Different emulgels, loaded with SILD co-evaporates, were formulated and characterized by different analyses including the viscosity, stability, spreadability, and in vitro release studies. Finally, the clinical activity of the chosen formula was accomplished via the application of the emulgels on volunteers suffering from erectile dysfunction. The results showed that the prepared SILD/PVP K90 of 1:2 w/w ratio exhibited the highest solubility and dissolution rate. All formulated emulgels exhibited good physicochemical properties. Especially, the emulgel formula composed of 2%w/v HPMC, loaded with SILD /PVP- K90, revealed the highest release rate. The release mechanism of SILD from emulgels fits with the Korsmeyer Peppas mechanism. The results of in vivo studies indicated a significant improvement of both IVLT and IIEF-5 parameters in mild to moderate ED, accompanied by PE. The modified SILD emulgel is an alternative promising and safe transdermal drug delivery system for the management and treatment of mild to moderate ED with PE.

Graphical Abstract

目前的工作重点是生产西地那非共蒸发负载乳液作为外用剂型治疗早泄和勃起功能障碍。局部施用柠檬酸西地那非（SILD）共蒸发物有望改善药物的生物利用度，并避免传统SILD剂型伴随的严重副作用，特别是对于禁用的心血管病例。首先，以PEG-5KDa和PVP-K90为亲水性载体，通过共蒸发技术提高了SILD的溶解度。通过DSC、XRD和溶解度研究对改性的共蒸发物进行了表征。不同的乳液，负载SILD共蒸发物，配制和表征不同的分析，包括粘度，稳定性，铺展性和体外释放研究。最后，所选配方的临床活动是通过将乳液应用于患有勃起功能障碍的志愿者来完成的。结果表明，制备的SILD/PVP K90在1:2 w/w比下具有最高的溶解度和溶出率。所配制的乳液均表现出良好的理化性能。其中，2%w/v HPMC的乳液配方，负载SILD /PVP- K90，其释放率最高。乳剂中SILD的释放机制符合Korsmeyer - Peppas机制。体内研究结果表明，轻度至中度ED伴PE时，IVLT和IIEF-5参数均有显著改善。改良的SILD乳凝胶是一种有前途和安全的经皮给药系统，用于管理和治疗轻至中度ED合并PE。图形抽象

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引用次数: 0

A Novel Facile and Efficient Prophylaxis Avenue of Chitosan Oligosaccharide/PLGA Based Polydatin Loaded Nanoparticles Against Bleomycin-Induced Lung Inflammation in Experimental Rat Model 低聚壳聚糖/PLGA负载多聚糖纳米颗粒对博莱霉素诱导大鼠肺炎症的一种新的简便有效的预防途径

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-16 DOI: 10.1208/s12249-024-03022-2

Ahmed Nashaat Alnagar, Amira Motawea, Randa A. Zaghloul, Mamdouh Eldesoqui, Irhan Ibrahim Abu Hashim

Lung inflammation is a hallmark of several respiratory diseases. Despite the great effectiveness of the synthetic antiinflammatory agents, they cause potential side effects. Polydatin (PD), a natural phytomedicine, has antioxidant and antiinflammatory effects. Its clinical applications are hindered due to poor aqueous solubility, low bioavailability, and rapid metabolism by first-pass effect. Herein, we report the development of a novel chitosan oligosaccharide-coated PD-loaded Poly dl-lactide-co-glycolide nanoparticles (COS-coated PD/PLGA NPs) against a bleomycin-induced pulmonary inflammation in a rat model. The NPs exhibited a small particle size of 188.57 ± 5.68 nm and a high zeta potential of + 18.13 ± 2.75 mV with spherical architecture and sustained release pattern of PD. In vivo studies in bleomycin-induced lung inflammation in a rat model revealed the superior prophylactic activity of COS-coated PD/PLGA NPs over the free drug (PD) as demonstrated by histopathological and immunohistochemical analyses, alongside biochemical assays evaluating oxidative stress biomarkers and inflammatory cytokine levels. Overall, the optimized COS-coated PD/PLGA NPs formulation offers a promising prophylactic platform against many respiratory diseases.

Graphical Abstract

肺部炎症是几种呼吸系统疾病的标志。尽管人工合成的抗炎药非常有效，但它们会产生潜在的副作用。多叶皂苷（PD）是一种天然植物药，具有抗氧化和抗炎作用。其水溶性差、生物利用度低、首过效应代谢快，阻碍了其临床应用。在此，我们报道了一种新型壳聚糖包被PD负载的聚dl-丙交酯-共糖醇纳米颗粒（cos包被PD/PLGA NPs）在大鼠模型中抗博莱霉素诱导的肺部炎症的发展。NPs的粒径为188.57±5.68 nm， zeta电位为+ 18.13±2.75 mV，呈球形结构，具有PD的缓释模式。在博莱霉素诱导的大鼠肺炎症模型的体内研究显示，通过组织病理学和免疫组织化学分析，以及评估氧化应激生物标志物和炎症细胞因子水平的生化分析，cos包被的PD/PLGA NPs比游离药物（PD）具有更好的预防活性。总的来说，优化的cos包被PD/PLGA NPs配方为预防许多呼吸系统疾病提供了一个有希望的平台。图形抽象

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引用次数: 0

Pediatric Formulation Optimization Using a Rational Design: Exploring Amorphous Solid Dispersion Technology with Terbinafine Hydrochloride as a Case Study 合理设计优化儿科配方：以盐酸特比萘芬为例探索非晶态固体分散技术

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-16 DOI: 10.1208/s12249-024-03012-4

Izabelle Amorim Ferreira Boza, Stéfani Laise da Silva, Nicolly Bittencourt Guedes, Giovana Carolina Bazzo, Hellen Karine Stulzer

Developing orally administered pediatric formulations presents significant challenges due to the unique characteristics of pediatric patients. Terbinafine hydrochloride (TER), a powerful antifungal agent, is effective against various fungal infections, including Tinea capitis, which is common in children. However, its low aqueous solubility necessitates innovative pharmaceutical strategies to enhance its effectiveness. This study describes a rational approach to selecting suitable carriers, approved for use in children, to increase the apparent solubility of TER and to guide the development of amorphous solid dispersions containing this drug. Assessments of solubility parameters, equilibrium solubility measurements, and calculations of pediatric dose numbers guided formulation development using theoretical and experimental methodologies. Carriers like Plasdone S-360 ULTRA®, HPMCAS L, and Soluplus® demonstrated favorable solubility parameter values with TER, indicating potential for drug solubilization. The solubility of TER was strongly dependent on pH. In buffer pH 6.5 containing 10% (w/v) of Soluplus®, TER presented the highest solubility value. The solid-state characterization techniques employed to assess the precipitate formed after equilibrium solubility studies during preformulation demonstrated that there were no phase transitions and no significant interactions between the drug and the evaluated carriers. Furthermore, the results demonstrate that Soluplus® achieved the lowest dose number (0.23) for pediatric patients over 6 years old. So, it was selected for preparing the amorphous solid dispersion via spray drying, which significantly enhanced the apparent solubility of TER while maintaining prolonged supersaturation, offering a promising alternative for developing solid formulations of this drug, particularly for pediatric patients, as it aims to improve oral bioavailability.

Graphical Abstract

由于儿科患者的独特特点，开发口服儿科配方提出了重大挑战。盐酸特比萘芬（TER）是一种强大的抗真菌剂，对各种真菌感染有效，包括儿童常见的头癣。然而，它的低水溶性需要创新的药物策略来提高其有效性。本研究描述了一种合理的方法来选择合适的载体，批准用于儿童，以增加TER的表观溶解度，并指导含有该药物的无定形固体分散体的发展。溶解度参数的评估、平衡溶解度测量和儿科剂量数的计算指导了使用理论和实验方法的配方开发。Plasdone S-360 ULTRA®、HPMCAS L和Soluplus®等载体在TER中表现出良好的溶解度参数值，表明具有药物增溶的潜力。TER的溶解度与pH密切相关，在含有10% (w/v) Soluplus®的pH 6.5缓冲液中，TER的溶解度最高。在预配制过程中，用于评估平衡溶解度研究后形成的沉淀的固态表征技术表明，药物与被评估的载体之间没有相变，也没有显著的相互作用。此外，结果表明，对于6岁以上的儿童患者，Soluplus®达到了最低的剂量数（0.23）。因此，我们选择通过喷雾干燥法制备无定形固体分散体，该方法显著提高了TER的表观溶解度，同时保持了长时间的过饱和状态，为开发该药物的固体配方提供了一个有希望的选择，特别是对于儿科患者，因为它旨在提高口服生物利用度。图形抽象

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引用次数: 0

Development of CPAP Overlay Interfaces for Efficient Administration of Aerosol Surfactant Therapy to Preterm Infants 用于早产儿气溶胶表面活性剂有效给药的CPAP覆盖界面的开发

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-16 DOI: 10.1208/s12249-024-02987-4

Hasan Jubaer, Sarah Strickler, Dale Farkas, Caleb Dalton, Mohammad A. M. Momin, Kelley M. Dodson, Michael Hindle, Worth Longest

The administration of surfactant aerosol therapy to preterm infants receiving continuous positive airway pressure (CPAP) respiratory support is highly challenging due to small flow passages, relatively high ventilation flow rates, rapid breathing and small inhalation volumes. To overcome these challenges, the objective of this study was to implement a validated computational fluid dynamics (CFD) model and develop an overlay nasal prong interface design for use with CPAP respiratory support that enables high efficiency powder aerosol delivery to the lungs of preterm infants when needed (i.e., on-demand) and can remain in place without increasing the work of breathing compared with a baseline CPAP interface. Realistic in vitro experiments were first conducted to generate baseline validation data, and then the CFD model, once validated, was used to explore key design parameters across a range of preterm infant nose-throat geometries and aerosol delivery conditions. The most important factors for efficient aerosol delivery were shown to be (i) maintaining the aerosol delivery flow rate below the tracheal flow rate (to minimize CPAP line loss) and (ii) concentrating the aerosol within the first portion of the inhalation waveform. An optimized design was shown to deliver approximately 37–60% of the nominal dose through the system and to the lungs with low intersubject variability (1050–2200 g infants) across two modes of device actuation (automated and manual) with room for further improvement. Ergonomic curvatures and streamlining of the prong geometries were also found to reduce work of breathing and flow resistance compared with a commercial alternative.

Graphical Abstract

对于接受持续气道正压通气（CPAP）呼吸支持的早产儿，表面活性剂气雾剂治疗具有很高的挑战性，因为其气道小，通气流速相对较高，呼吸急促，吸入量小。为了克服这些挑战，本研究的目的是实施一个经过验证的计算流体动力学（CFD）模型，并开发一种覆盖鼻尖接口设计，用于CPAP呼吸支持，能够在需要时（即按需）高效地将粉末气溶胶输送到早产儿的肺部，并且与基线CPAP接口相比，可以保持在适当的位置，而不会增加呼吸工作。首先进行实际的体外实验以生成基线验证数据，然后使用CFD模型，一旦验证，用于探索一系列早产儿鼻-喉几何形状和气溶胶输送条件的关键设计参数。有效气溶胶输送的最重要因素被证明是(i)保持气溶胶输送流速低于气管流速（以尽量减少CPAP线路损耗）和（ii）将气溶胶集中在吸入波形的第一部分。优化设计表明，通过两种装置驱动模式（自动和手动），通过系统和肺部提供约37-60%的标称剂量，受试者间可变性低（1050-2200 g婴儿），并有进一步改进的空间。与商业替代品相比，符合人体工程学的曲率和尖头几何形状的流线型也减少了呼吸和流动阻力的工作。图形抽象

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引用次数: 0

Microfluidic Approach for Enhanced Paeoniflorin Transdermal Delivery: A Comparative Study on Different Chips and Mixing Dynamics 微流控方法增强芍药苷透皮给药：不同芯片和混合动力学的比较研究

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-16 DOI: 10.1208/s12249-024-03033-z

Qifei Gu, Wuqing Xiao, Yingyin Zhu, Wanling Zhong, Xue Sui, Yongchao Liu, Jie Zhang, Huichao Wu, Rui Zhou

Paeoniflorin is a natural pharmaceutical ingredient with a widely biological activity. However, as a hydrophilic drug, the problem of low transdermal rate limits its clinical application. To overcome this shortage, LUVs were used as biocompatible carriers of paeoniflorin in this study. We prepared paeoniflorin-loaded large unilamellar vesicles (LUVs) with W/O/W structure by microfluidics. We used four kinds of chips to prepare paeoniflorin LUVs and explored the effects of the chip structures on LUVs properties applying both experiments and numerical simulations. The difference of fluid mixing mechanisms was analyzed among four different channels, including straight and curved structures. Then we evaluated the differences in skin permeability among the three groups, paeoniflorin aqueous solution group, drug-loaded liposome group and blank liposome & drug mixture group, using the abdominal skin of male mice. The results showed that the structure of the microfluidic channel was a key factor affecting the flow rate and mixing efficiency. The mixing efficiency further affected the liposome size. The mixing efficiency of curved channel was not better than that of a straight channel due to the low flow rate and long mixing time. By the results of transdermal experiments, LUVs could reduce the transdermal time and increase the total transdermal amount. LUVs effectively improved the transdermal absorption efficiency of paeoniflorin. In conclusion, paeoniflorin LUVs with highly efficient transdermal were successfully prepared by using microfluidics. We explored the underlying fluid dynamics that lead to variations in the preparation with different chip structures. The transdermal effect of the LUVs was verified.

Graphical Abstract

芍药苷是一种具有广泛生物活性的天然药物成分。然而，作为一种亲水性药物，透皮率低的问题限制了其临床应用。为了克服这一不足，本研究将luv作为芍药苷的生物相容性载体。采用微流体技术制备了W/O/W结构的芍药苷大单层囊泡（LUVs）。采用四种芯片制备了芍药苷luv，并通过实验和数值模拟探讨了芯片结构对luv性能的影响。分析了四种不同通道（包括直通道和弯通道）流体混合机理的差异。然后观察芍药苷水溶液组、载药脂质体组和空白脂质体组小鼠皮肤通透性的差异；药物混合组，使用雄性小鼠腹部皮肤。结果表明，微流控通道的结构是影响流量和混合效率的关键因素。混合效率进一步影响了脂质体的大小。由于流量小，混合时间长，曲线通道的混合效率并不比直线通道好。透皮实验结果表明，luv可缩短透皮时间，增加透皮总量。LUVs有效提高了芍药苷的透皮吸收效率。综上所述，利用微流体技术成功制备了高效透皮的芍药苷luv。我们探索了导致不同芯片结构制备变化的潜在流体动力学。验证了luv的透皮效应。图形抽象

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引用次数: 0

Silica Nanoparticles: A Promising Vehicle for Anti-Cancer Drugs Delivery 二氧化硅纳米颗粒：一种有前途的抗癌药物递送载体

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-13 DOI: 10.1208/s12249-024-02982-9

T. Naga Aparna, Rohit Kumar, Shah Raj Ali, Dhaval J. Patel, Kazi Julekha, Touseef Begum, Jyoti Bala, Pawan Kumar

The prevalence and death due to cancer have been rising over the past few decades, and eliminating tumour cells without sacrificing healthy cells remains a difficult task. Due to the low specificity and solubility of drug molecules, patients often require high dosages to achieve the desired therapeutic effects. Silica nanoparticles (SiNPs) can effectively deliver therapeutic agents to targeted sites in the body, addressing these challenges. Using SiNPs as vehicles for anti-cancer drug delivery has emerged as a promising strategy due to their unique structural properties, biocompatibility, and versatility. This review explores the various aspects of SiNPs in cancer therapy, highlighting their synthesis, functionalization, and application in delivering chemotherapeutic agents, photosensitizers, and nucleic acids. SiNPs offer advantages such as high drug loading capacity, controlled release, and targeted delivery, enhancing therapeutic efficacy and reducing systemic toxicity. Moreover, this review aims to provide an in-depth understanding of the current state and prospects of SiNPs in revolutionizing cancer treatment and improving patient outcomes.

Graphical Abstract

在过去的几十年里，癌症的发病率和死亡率一直在上升，在不牺牲健康细胞的情况下消灭肿瘤细胞仍然是一项艰巨的任务。由于药物分子的特异性和溶解度较低，患者往往需要高剂量才能达到预期的治疗效果。二氧化硅纳米颗粒（SiNPs）可以有效地将治疗剂输送到体内的目标部位，从而解决了这些挑战。由于其独特的结构特性、生物相容性和多功能性，使用sinp作为抗癌药物递送的载体已成为一种有前途的策略。本文综述了SiNPs在癌症治疗中的各个方面，重点介绍了它们的合成、功能化以及在传递化疗药物、光敏剂和核酸方面的应用。sinp具有载药能力强、释放可控、靶向给药、提高治疗效果、降低全身毒性等优点。此外，本综述旨在深入了解SiNPs在革新癌症治疗和改善患者预后方面的现状和前景。图形抽象

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引用次数: 0

Correction: From Bench to Bedside: ROS-Responsive Nanocarriers in Cancer Therapy 更正：从实验室到床边：肿瘤治疗中的ros反应性纳米载体

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-13 DOI: 10.1208/s12249-024-03036-w

Abhishek Chauhan, Raj Kamal, Rohit Bhatia, Thakur Gurjeet Singh, Ankit Awasthi

引用次数: 0

Understanding Microemulsions and Nanoemulsions in (Trans)Dermal Delivery 了解微乳液和纳米乳液在（经）皮递送中的作用

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-10 DOI: 10.1208/s12249-024-02997-2

Jasmine Musakhanian, David W. Osborne

Continuously explored in pharmaceuticals, microemulsions and nanoemulsions offer drug delivery opportunities that are too significant to ignore, namely safe delivery of clinically relevant drug doses across biological membranes. Their effectiveness as drug vehicles in mucosal and (trans)dermal delivery is evident from the volume of published literature. Commonly, their ability to enhance skin permeation is attributed to dispersion size, a characteristic closely related to solubilization capacity. However, the literature falls short on distinctions between microemulsions and nanoemulsions for definitions, behavior, or specific differences in their mechanisms of action in (trans)dermal delivery. The focus is typically on surfactant/cosurfactant ratio and droplet size but the role of mesostructures or the effect of cosolvent (C_sol), oil (O) or water (W) on permeation profile remain poorly explained. Towards a deeper understanding of these vehicles in (trans)dermal drug delivery, this review begins with their conceptual and practical distinctions before delving into the published works for less obvious but potentially important underlying mechanisms; notably composition and the competitive positioning of system constituents in the resulting microstructures and subsequent effect(s) these may have on skin structures and drug permeability. For practical purposes, this review focuses on formulation systems based on ternary diagrams with commonly accepted non-ionic surfactants, cosurfactants, cosolvents, and oils used in pharmaceutical applications.

Graphical Abstract

在制药领域，微乳和纳米乳不断被探索，提供了不容忽视的药物递送机会，即通过生物膜安全递送临床相关药物剂量。它们在粘膜和（跨）皮肤递送中作为药物载体的有效性从已发表的文献中可以明显看出。通常，它们增强皮肤渗透的能力归因于分散大小，这一特性与增溶能力密切相关。然而，文献缺乏微乳液和纳米乳液之间的定义，行为，或在（反）皮肤递送中的作用机制的具体差异的区别。重点通常是表面活性剂/助表面活性剂的比例和液滴大小，但介观结构的作用或助溶剂（Csol）、油(O)或水(W)对渗透剖面的影响仍然没有得到很好的解释。为了更深入地了解这些（经）皮药物输送的载体，本综述从它们的概念和实践区别开始，然后深入研究已发表的不太明显但潜在重要的潜在机制；值得注意的是，系统成分在所产生的微观结构中的组成和竞争性定位，以及这些可能对皮肤结构和药物渗透性产生的后续影响。为了实际的目的，这篇综述的重点是基于三元图的配方系统与普遍接受的非离子表面活性剂，共表面活性剂，共溶剂，以及在制药应用中使用的油。图形抽象

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引用次数: 0

Advancements in Transdermal Drug Delivery Systems: Harnessing the Potential of Macromolecular Assisted Permeation Enhancement and Novel Techniques 经皮给药系统的进展：利用大分子辅助渗透增强的潜力和新技术

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-01-09 DOI: 10.1208/s12249-024-03029-9

Pratikeswar Panda, Tejaswini Mohanty, Rajaram Mohapatra

Transdermal drug delivery (TDD) represents a transformative paradigm in drug administration, offering advantages such as controlled drug release, enhanced patient adherence, and circumvention of hepatic first-pass metabolism. Despite these benefits, the inherent barrier function of the skin, primarily attributed to the stratum corneum, remains a significant impediment to the efficient permeation of therapeutic agents. Recent advancements have focused on macromolecular-assisted permeation enhancers, including carbohydrates, lipids, amino acids, nucleic acids, and cell-penetrating peptides, which modulate skin permeability by transiently altering its structural integrity. Concurrently, innovative methodologies such as iontophoresis, electroporation, microneedles, ultrasound, and sonophoresis have emerged as potent tools to enhance drug transport by creating transient microchannels or altering the skin's microenvironment. Among the novel approaches, the development of nanocarriers such as Liposome, niosomes, and transethosomes etc. has garnered substantial attention. These elastic vesicular systems, comprising lipids and edge activators, exhibit superior skin penetration owing to their deformability and enhanced payload delivery capabilities. Furthermore, the integration of nanocarriers with physical enhancement techniques demonstrates a synergistic potential, effectively addressing the limitations of conventional TDD systems. This comprehensive convergence of macromolecular-assisted enhancers, advanced physical techniques, and next-generation nanocarriers underscores the evolution of TDD, paving the way for optimized therapeutic outcomes.

Graphical Abstract

经皮给药（TDD）代表了药物管理的变革范式，具有诸如药物释放控制，增强患者依从性和绕过肝脏第一过代谢等优点。尽管有这些好处，皮肤固有的屏障功能，主要归因于角质层，仍然是治疗药物有效渗透的一个重大障碍。最近的进展集中在大分子辅助渗透增强剂上，包括碳水化合物、脂质、氨基酸、核酸和细胞穿透肽，它们通过短暂改变皮肤结构完整性来调节皮肤的渗透性。同时，离子电泳、电穿孔、微针、超声和声电泳等创新方法已经成为通过创建瞬时微通道或改变皮肤微环境来增强药物运输的有效工具。在这些新方法中，纳米载体如脂质体、乳质体和转运体等的发展引起了人们的广泛关注。这些弹性囊泡系统由脂质和边缘激活剂组成，由于其可变形性和增强的有效载荷传递能力，表现出优越的皮肤穿透性。此外，纳米载体与物理增强技术的集成展示了协同潜力，有效地解决了传统TDD系统的局限性。这种大分子辅助增强剂、先进物理技术和下一代纳米载体的全面融合强调了TDD的发展，为优化治疗结果铺平了道路。图形抽象

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