Controlled delivery

受控交付
  • 文章类型: Journal Article
    目前雄激素性脱发的药理学管理不方便,需要患者难以遵循的学科。这降低了对治疗的依从性和对结果的满意度。重要的是提出增加患者依从性和减少不良反应的治疗方案。这项工作描述了部分包封在β-环糊精中并通过光声波辅助的米诺地尔的透皮递送。光声波瞬时增加皮肤的渗透性并允许递送包封的米诺地尔。开发了米诺地尔凝胶制剂,并在存在和不存在光声波的情况下进行了体外透皮给药研究。由光-压力换能器产生的光声波的5分钟刺激使米诺地尔透皮递送通量增加约3倍。由光声波促进的1%米诺地尔制剂的通量类似于2%米诺地尔商业制剂的被动通量。米诺地尔从β-环糊精的释放增加了皮肤暴露,而不增加峰值全身暴露。这促进了头发生长,减少了治疗和副作用。使用封装的米诺地尔和光声波的体内研究产生了86%的头发外套恢复(与对照组为29%),血压无变化。
    The current pharmacological management of androgenetic alopecia is inconvenient and requires a discipline that patients find difficult to follow. This reduces compliance with treatment and satisfaction with results. It is important to propose treatment regimens that increase patient compliance and reduce adverse effects. This work describes transdermal delivery of minoxidil partially encapsulated in β-cyclodextrin and assisted by photoacoustic waves. Photoacoustic waves transiently increase the permeability of the skin and allow for the delivery of encapsulated minoxidil. A minoxidil gel formulation was developed and the transdermal delivery was studied in vitro in the presence and absence of photoacoustic waves. A 5-min stimulus with photoacoustic waves generated by light-to-pressure transducers increases minoxidil transdermal delivery flux by approximately 3-fold. The flux of a 1% minoxidil formulation promoted by photoacoustic waves is similar to the passive flux of a 2% minoxidil commercial formulation. Release of minoxidil from β-cyclodextrin increases dermal exposure without increasing peak systemic exposure. This promotes hair growth with fewer treatments and reduced adverse effects. In vivo studies using encapsulated minoxidil and photoacoustic waves yielded 86% hair coat recovery (vs. 29% in the control group) and no changes in the blood pressure.
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  • 文章类型: Journal Article
    免疫疗法已经成为一种有希望的癌症治疗方法,提供提高的生存率和提高患者的生活质量。然而,在临床实践中实现免疫治疗的全部潜力仍然是一个挑战,因为仍然有足够的空间来调节人类免疫系统的复杂性,以支持抗肿瘤免疫原性。纳米技术,凭借其独特的属性,有望增强癌症免疫疗法在生物治疗保护以及免疫调节剂生物制剂的位点和时间控制递送中的功效。聚合物纳米粒子是有前途的生物材料在不同的纳米载体由于其鲁棒性,多功能性,和成本效益的设计和生产。这篇透视论文概述了应用于癌症免疫治疗的纳米先进递送系统的关键概念。我们专注于对当前技术水平的详细探索,以及将聚(β-氨基酯)(pBAE)聚合物用于基于核酸的抗肿瘤免疫疗法的趋势。通过文献中报道的使用pBAE聚合物的不同实例,我们修改了这些聚合物提供的主要优势和一些需要克服的挑战。最后,本文提供了对癌症纳米免疫疗法的临床实施路径的见解和预测,强调pBAE聚合物在这一领域取得进展的潜力。
    Immunotherapy has emerged as a promising approach to cancer treatment, offering improved survival rates and enhanced patients\' quality of life. However, realizing the full potential of immunotherapy in clinical practice remains a challenge, as there is still plenty of room for modulating the complexity of the human immune system in favor of an antitumor immunogenicity. Nanotechnology, with its unique properties, holds promise in augmenting the efficacy of cancer immunotherapies in biotherapeutic protection and site- and time-controlled delivery of the immune modulator biologicals. Polymeric nanoparticles are promising biomaterials among different nanocarriers thanks to their robustness, versatility, and cost-efficient design and production. This perspective paper overviews critical concepts in nanometric advanced delivery systems applied to cancer immunotherapy. We focus on a detailed exploration of the current state of the art and trends in using poly(beta-aminoester) (pBAE) polymers for nucleic acid-based antitumor immunotherapies. Through different examples of the use of pBAE polymers reported in the literature, we revise the main advantages these polymers offer and some challenges to overcome. Finally, the paper provides insights and predictions on the path toward the clinical implementation of cancer nano-immunotherapies, highlighting the potential of pBAE polymers for advancements in this field.
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  • 文章类型: Journal Article
    近年来,抗生素耐药性已成为医疗保健的紧迫威胁。药物递送系统的使用提供优于常规抗生素施用的优点,并且可以减缓抗生素抗性的发展。在目前的研究中,我们开发了一种毒素触发的脂质体抗生素递送系统,其中药物释放是由革兰氏阴性病原体产生的白细胞毒素(LtxA)实现的,放线菌聚集杆菌。LtxA先前已被证明通过促进非层状脂质的脂质相变来介导膜破坏,例如1,2-二油酰基-sn-甘油基-3-磷酸乙醇胺-N-甲基(N-甲基-DOPE)。此外,已观察到LtxA与含有大量胆固醇的膜强烈且几乎不可逆地结合。这里,我们设计了由N-甲基-DOPE和胆固醇组成的脂质体递送系统,以利用这些相互作用.具体来说,我们假设由N-甲基-DOPE和胆固醇组成的脂质体,封装抗生素,会对LtxA敏感,能够控制抗生素的释放。我们观察到由N-甲基-DOPE组成的脂质体对低浓度的LtxA的存在敏感,胆固醇增加了内容物释放的程度和动力学。脂质体在各种储存条件下稳定至少7天。最后,我们表明,抗生素的释放在放线菌群产生LtxA的菌株存在下选择性地发生,但在非LtxA表达菌株存在下不发生。一起,这些结果表明,设计的脂质体载体能够将毒素触发的抗生素递送至产生LtxA的放线菌群。
    Antibiotic resistance has become an urgent threat to health care in recent years. The use of drug delivery systems provides advantages over conventional administration of antibiotics and can slow the development of antibiotic resistance. In the current study, we developed a toxin-triggered liposomal antibiotic delivery system, in which the drug release is enabled by the leukotoxin (LtxA) produced by the Gram-negative pathogen, Aggregatibacter actinomycetemcomitans. LtxA has previously been shown to mediate membrane disruption by promoting a lipid phase change in nonlamellar lipids, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-methyl (N-methyl-DOPE). In addition, LtxA has been observed to bind strongly and nearly irreversibly to membranes containing large amounts of cholesterol. Here, we designed a liposomal delivery system composed of N-methyl-DOPE and cholesterol to take advantage of these interactions. Specifically, we hypothesized that liposomes composed of N-methyl-DOPE and cholesterol, encapsulating antibiotics, would be sensitive to LtxA, enabling controlled antibiotic release. We observed that liposomes composed of N-methyl-DOPE were sensitive to the presence of low concentrations of LtxA, and cholesterol increased the extent and kinetics of content release. The liposomes were stable under various storage conditions for at least 7 days. Finally, we showed that antibiotic release occurs selectively in the presence of an LtxA-producing strain of A. actinomycetemcomitans but not in the presence of a non-LtxA-expressing strain. Together, these results demonstrate that the designed liposomal vehicle enables toxin-triggered delivery of antibiotics to LtxA-producing strains of A. actinomycetemcomitans.
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  • 文章类型: Journal Article
    癌症是全球死亡的主要原因,化疗是一种关键的治疗方法,单独或与其他疗法联合使用。这些疗法的主要目标是抑制癌细胞的生长,同时尽量减少对健康分裂细胞的伤害。常规治疗因其副作用而受到阻碍,经常给患者带来严重的不适。研究人员一直在探索选择性靶向癌细胞的创新方法。在这种情况下,基于生物聚合物的气凝胶作为创新平台出现,展示对不同刺激做出智能反应的独特属性,包括温度,pH值变化,磁场,和氧化还原电位。这种反应能够精确控制抗癌药物的释放,提高治疗效果。这些气凝胶的意义在于它们能够提供具有增加功效的靶向药物递送。生物相容性,和高药物有效载荷。在这次全面审查中,我们讨论了基于生物聚合物的气凝胶作为抗癌药物递送中新兴的功能化平台的作用。该综述讨论了基于生物聚合物的气凝胶的独特特性,显示了它们在响应包括温度在内的不同刺激时的智能行为。pH值,磁性和氧化还原电位来控制抗癌药物的释放。最后,这篇综述讨论了基于生物聚合物的气凝胶在递送不同抗癌药物中的应用,并讨论了这些平台在基因递送应用中的潜力。本文受版权保护。保留所有权利。
    Cancer stands as a leading cause of global mortality, with chemotherapy being a pivotal treatment approach, either alone or in conjunction with other therapies. The primary goal of these therapies is to inhibit the growth of cancer cells specifically, while minimizing harm to healthy dividing cells. Conventional treatments, often causing patient discomfort due to side effects, have led researchers to explore innovative, targeted cancer cell therapies. Thus, biopolymer-based aerogels emerge as innovative platforms, showcasing unique properties that respond intelligently to diverse stimuli. This responsiveness enables precise control over the release of anticancer drugs, enhancing therapeutic outcomes. The significance of these aerogels lies in their ability to offer targeted drug delivery with increased efficacy, biocompatibility, and a high drug payload. In this comprehensive review, the author discuss the role of biopolymer-based aerogels as an emerging functionalized platforms in anticancer drug delivery. The review addresses the unique properties of biopolymer-based aerogels showing their smart behavior in responding to different stimuli including temperature, pH, magnetic and redox potential to control anticancer drug release. Finally, the review discusses the application of different biopolymer-based aerogel in delivering different anticancer drugs and also discusses the potential of these platforms in gene delivery applications.
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  • 文章类型: Journal Article
    抗生素给药是牙周炎治疗中指导组织再生(GTR)的相邻疗法。这是由于病原体生物膜在加重牙周缺损中的主要作用。本研究旨在制造用于持续递送盐酸多西环素(DOX)同时具有空间保持功能的GTR膜。通过静电纺丝技术使用聚己内酯/聚乙烯醇/壳聚糖的聚合物共混物制备膜。所获得的膜在物理化学和生物学性质方面进行了表征。纳米纤维显示出<450nm的亚微米范围内的平均直径,同时具有均匀的随机排列的形态。所获得的膜显示出高强度和柔性。对于制造的制剂,观察到在68小时内延长的体外释放曲线。制备的膜在不同DOX浓度下显示>70%的细胞活力。该制剂对引起牙周炎的常见病原体具有抗微生物功效。体内评估也显示了14天的DOX的延长释放。组织病理学评价证实了GTR膜的生物相容性。总之,开发的负载DOX的纳米纤维GTR膜可能具有有利于持续抗生素递送和通过空间保持功能的牙周再生而不引起任何刺激和组织损伤的有益特征。
    Antibiotic administration is an adjacent therapy to guided tissue regeneration (GTR) in the management of periodontitis. This is due to the major role of pathogen biofilm in aggravating periodontal defects. This study aimed to fabricate a GTR membrane for sustained delivery of doxycycline hydrochloride (DOX) while having a space-maintaining function. The membranes were prepared using a polymeric blend of polycaprolactone/polyvinyl alcohol/chitosan by the electrospinning technique. The obtained membranes were characterized in terms of physicochemical and biological properties. Nanofibers showed a mean diameter in the submicron range of < 450 nm while having uniform randomly aligned morphology. The obtained membranes showed high strength and flexibility. A prolonged in vitro release profile during 68 h was observed for manufactured formulations. The prepared membranes showed a cell viability of > 70% at different DOX concentrations. The formulations possessed antimicrobial efficacy against common pathogens responsible for periodontitis. In vivo evaluation also showed prolonged release of DOX for 14 days. The histopathological evaluation confirmed the biocompatibility of the GTR membrane. In conclusion, the developed nanofibrous DOX-loaded GTR membranes may have beneficial characteristics in favour of both sustained antibiotic delivery and periodontal regeneration by space-maintaining function without causing any irritation and tissue damage.
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  • 文章类型: Journal Article
    这项研究的目的是将分子印迹聚合物(MIPs)评估为环丙沙星的控释系统。通过三种不同的方法进行MIPs合成:乳液,散装,和共沉淀。乳酸(LA)和甲基丙烯酸(MA)用作功能单体,乙二醇二甲基丙烯酸酯用作交联剂。此外,合成了非印迹聚合物(NIPs)。MIP和NIP通过扫描电子显微镜进行表征,傅里叶变换红外反射,比表面积,孔径,和释放动力学。它们对金黄色葡萄球菌和大肠杆菌的功效,并证明了它们在真皮成纤维细胞中的细胞毒性。结果表明,MIP是介孔材料,孔径在10至20nm之间。发现以MA为单体的共沉淀MIP具有更高的吸附。释放动力学证明发生了非Fickian过程,并且与LA共沉淀的MIP在8h内表现出最高的释放速率(90.51mg/L)。金黄色葡萄球菌的最低抑菌浓度为0.031至0.016mg/L,大肠杆菌的最低抑菌浓度为0.004至0.031mg/L。在细胞培养物中没有发现细胞毒性;此外,细胞生长是有利的。这项研究表明,MIP为药物施用及其在临床实践中的应用提供了有希望的特性。
    The aim of this study was the molecular imprinting polymers (MIPs) assessment as a controlled release system of ciprofloxacin. The MIPs synthesis was performed by three different methods: emulsion, bulk, and co-precipitation. Lactic acid (LA) and methacrylic acid (MA) were used as functional monomers and ethylene glycol dimethacrylate as crosslinker. Also, nonimprinted polymers (NIPs) were synthesized. MIPs and NIPs were characterized by scanning electron microscopy, Fourier Transform Infrared Reflection, specific surface area, pore size, and release kinetics. Their efficiency against Staphylococcus aureus and Escherichia coli, and their cytotoxicity in dermal fibroblast cells were proven. Results show that MIPs are mesoporous materials with a pore size between 10 and 20 nm. A higher adsorption with the co-precipitation MIP with MA as a monomer was found. The release kinetics proved that a non-Fickian process occurred and that the co-precipitation MIP with LA presented the highest release rate (90.51 mg/L) in 8 h. The minimum inhibitory concentration was found between 0.031 and 0.016 mg/L for Staphylococcus aureus and between 0.004 and 0.031 mg/L for the Escherichia coli. No cytotoxicity in cellular cultures was found; also, cellular growth was favored. This study demonstrated that MIPs present promising properties for drug administration and their application in clinical practice.
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  • 文章类型: Journal Article
    多糖是食品级口服给药系统领域的一个突出的选择,因为它们抵抗消化酶在口服,胃,和小肠环境,以及它们易于生产,成本效益,和作为益生元的潜在健康益处。此外,它们对pH诱导的溶解反应的能力,以及它们的乳化特性,可以策略性地用于实现亲脂性生物活性物质对小肠的精确靶向。在这项研究中,柑橘皮果胶和藻酸盐可用作乳液颗粒的稳定剂,而无需补充乳化剂或胶凝剂。在这个系统中,果胶作为乳化剂,而海藻酸盐充当胶凝剂,由Ca2+诱导的离子交联促进。果胶和藻酸盐之间的协同相互作用有效地保护了姜黄素在胃病和小肠中的受控溶解。取决于果胶/藻酸盐的比例。这些受控现象促进了脂解,姜黄素释放,并最终增强姜黄素的生物可获得性。此外,一旦乳化颗粒释放出小肠中所有的姜黄素,果胶酶和藻酸盐裂解酶容易降解残留的多糖,产生可发酵的单糖。这证实了乳化凝胶颗粒在结肠中用作益生元的潜力。这些发现为增强封装亲脂性生物活性物质的食品级递送系统的系统设计提供了重要的前景。实现控制释放,增强稳定性,和改善生物可及性。重要的是,该系统可以包括经过完全消化的组件,吸收,以及在人体中的利用,包括石油等材料,营养食品,和益生元,所有这些都不会带来健康风险。
    Polysaccharides are a prominent choice in the realm of food-grade oral delivery systems due to their resistance to degradation by digestive enzymes in the oral, gastric, and small intestinal environments, as well as their ease of production, cost-effectiveness, and potential health benefits as prebiotics. Furthermore, their ability to respond to pH-induced dissolution, along with their emulsifying properties, can be strategically employed to achieve precise targeting of lipophilic bioactives to the small intestine. In this study, citrus peel pectin and alginate served as stabilizers for emulgel particles without supplementary emulsifiers or gelling agents. Within this system, pectin functioned as an emulsifier, while alginate acted as a gelling agent, facilitated by Ca2+-induced ionic crosslinking. The synergistic interplay between pectin and alginate efficiently protected curcumin in gastric conditions and controlled dissolution in the small intestine, depending on the pectin/alginate ratio. These controlled phenomena facilitated lipolysis, curcumin release, and ultimately enhanced curcumin bioaccessibility. Furthermore, once the emulgel particle released all the entrapped curcumin in the small intestine, residual polysaccharides underwent facile degradation by pectinase and alginate lyase, yielding fermentable monosaccharides. This confirms the potential of the emulgel particles for use as a prebiotic in the colon. These findings offer significant promise for enhancing the systematic design of food-grade delivery systems that encapsulate lipophilic bioactives, achieving controlled release, enhanced stability, and improved bioaccessibility. Importantly, this system can comprise components that undergo complete digestion, absorption, and utilization in the human body, encompassing materials such as oil, nutraceuticals, and prebiotics, all without presenting health risks.
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  • 文章类型: Journal Article
    天然材料是各向异性的。自然界中出现的输送系统,如病毒,血细胞,花粉,和许多其他人,确实有各向异性,而人工制造的输送系统大多是各向同性的。在设计具有微米和亚微米尺寸的各向异性颗粒或胶囊时存在明显的复杂性。然而,已经开发了如何制造具有各向异性形状或具有各向异性化学和/或物理性质的颗粒的一些有希望的示例。粒子的各向异性,一旦他们面对生物系统,影响他们的行为。细胞的内部化,在血液中流动,器官和组织的生物分布,定向释放,和颗粒的毒性,而不管相同的化学性质,都被报道为递送系统的各向异性的因素。这里,我们回顾了当前将各向异性引入颗粒或胶囊的方法,包括装载各种治疗货物,可变的物理性质主要由各向异性磁性,控制方向运动,制造Janus粒子.在一个实体中组合不同的各向异性以用于递送的优点以及制造的常见问题和限制正在讨论中。本文受版权保护。保留所有权利。
    Natural materials are anisotropic. Delivery systems occurring in nature, such as viruses, blood cells, pollen, and many others, do have anisotropy, while delivery systems made artificially are mostly isotropic. There is apparent complexity in engineering anisotropic particles or capsules with micron and submicron sizes. Nevertheless, some promising examples of how to fabricate particles with anisotropic shapes or having anisotropic chemical and/or physical properties are developed. Anisotropy of particles, once they face biological systems, influences their behavior. Internalization by the cells, flow in the bloodstream, biodistribution over organs and tissues, directed release, and toxicity of particles regardless of the same chemistry are all reported to be factors of anisotropy of delivery systems. Here, the current methods are reviewed to introduce anisotropy to particles or capsules, including loading with various therapeutic cargo, variable physical properties primarily by anisotropic magnetic properties, controlling directional motion, and making Janus particles. The advantages of combining different anisotropy in one entity for delivery and common problems and limitations for fabrication are under discussion.
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  • 文章类型: Journal Article
    绿原酸(CGA)是一种重要的生物活性多酚,具有广泛的生物学特性。本研究旨在制造优化的三维(3D)打印胶囊支架和CGA胶囊,用于将疏水性CGA靶向递送至结肠。使用神经网络模型确定的优化打印参数是170°C的温度,20毫米/秒的印刷速度,喷嘴直径为0.3mm。胶囊表现出CGA的缓释特性,Eudragit®FS30D密封胶囊的释放速率(由于更多的裂缝和空隙)比Eudragit®S100密封胶囊的释放速率更快。Ritger-peppas模型是描述8个CGA胶囊(R2≥0.98)中CGA释放过程的最佳拟合模型。所有CGA胶囊均表现出剪切稀化特性,在低剪切速率下具有稳定的溶胶-凝胶粘度。FTIR光谱证实在CGA和溶胶之间形成非共价键。总的来说,获得的3D打印胶囊为个性化膳食补充剂的开发中CGA的靶向递送提供了有希望的载体。
    Chlorogenic acid (CGA) is an important bioactive polyphenol with extensive biological properties. This study aimed to fabricate an optimized three-dimensional (3D)-printed capsule scaffold and CGA capsules for targeted delivery of hydrophobic CGA to the colon. The optimized printing parameters identified using the neural network model were a temperature of 170 °C, a printing speed of 20 mm/s, and a nozzle diameter of 0.3 mm. The capsules exhibited slow releasing properties of CGA, and the releasing rates of Eudragit®FS 30D-sealed capsules (due to more cracks and voids) were faster than those of Eudragit®S100-sealed capsules. The Ritger-peppas model was the best fitting model to describe the releasing process of CGA from 8 CGA capsules (R2 ≥ 0.98). All CGA capsules exhibited shear-thinning properties with stable sol-gel viscosity at low shear rates. FTIR spectra confirmed the formation of non-covalent bonds between CGA and the sol. Overall, the obtained 3D-printed capsules provided a promising carrier for the targeted delivery of CGA in the development of personalized dietary supplements.
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  • 文章类型: Journal Article
    在各种药物递送系统中,固体脂质纳米颗粒主要是基于脂质的纳米载体。盐酸胺碘酮是一种抗心律失常药,用于治疗严重的节律紊乱。由于其低溶解度和高渗透性,它在胃肠道中具有可变且难以预测的吸收。这项研究的目的是通过使用两种赋形剂-Compritol®888ATO(颗粒)(C888)作为脂质基质和Transcutol®(T)作为表面活性剂将胺碘酮包封到固体脂质纳米颗粒中来提高其溶解度。使用热均质化技术获得六种类型的负载胺碘酮的固体脂质纳米颗粒(AMD-SLN),然后使用不同的超声处理参数进行超声处理。AMD-SLN的特征在于它们的大小分布,多分散指数,zeta电位,截留效率,和药物装载。基于对截留效率的初步评估,仅三种固体脂质纳米颗粒制剂(P1、P3和P5)被进一步测试。通过扫描电子显微镜对它们进行了评估,傅里叶变换红外光谱法,近红外光谱法,热重分析,差示扫描量热法,和体外溶出度测试。P5配方显示出最佳的药物技术性能,并且它具有最大的潜力用于口服药物产品,用于控制胺碘酮的递送。
    In various drug delivery systems, solid lipid nanoparticles are dominantly lipid-based nanocarriers. Amiodarone hydrochloride is an antiarrhythmic agent used to treat severe rhythm disturbances. It has variable and hard-to-predict absorption in the gastrointestinal tract because of its low solubility and high permeability. The aims of this study were to improve its solubility by encapsulating amiodarone into solid lipid nanoparticles using two excipients-Compritol® 888 ATO (pellets) (C888) as a lipid matrix and Transcutol® (T) as a surfactant. Six types of amiodarone-loaded solid lipid nanoparticles (AMD-SLNs) were obtained using a hot homogenization technique followed by ultrasonication with varying sonication parameters. AMD-SLNs were characterized by their size distribution, polydispersity index, zeta potential, entrapment efficiency, and drug loading. Based on the initial evaluation of the entrapment efficiency, only three solid lipid nanoparticle formulations (P1, P3, and P5) were further tested. They were evaluated through scanning electron microscopy, Fourier-transform infrared spectrometry, near-infrared spectrometry, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The P5 formulation showed optimum pharmaco-technical properties, and it had the greatest potential to be used in oral pharmaceutical products for the controlled delivery of amiodarone.
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