Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

Insights on drug and gene delivery systems in liver fibrosis

Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.

Advanced nano drug delivery systems for neuroprotection against ischemic stroke

Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability rates.The efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited bioavailability.Conversely,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug concentrations.This review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of IS.By examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery systems.Leveraging these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.

Loading of tacrolimus containing lipid based drug delivery systems into mesoporous silica for extended release

Many studies had been focused on designing tacrolimus sustained release preparations based on solid dispersion technique, but no one had tried to employ mesoporous silica as the carrier material to realize this goal. The purpose of this study was to develop a novel, simple and environmental friendly drug loading method with mesoporous silica to obtain tacrolimus sustained-release preparation. Tacrolimus was firstly dissolved in the molten mixed lipid composed of Compritol 888 ATO and Gelucire 50/13 to prepare a drug loaded lipid-based drug delivery systems(LBDDS), then the liquid LBDDS was adsorbed by mesoporous silica to transfer the liquid into solid powder, ie. the tacrolimus sustained release silica-lipid hybrid(SLH). The SLH was characterized by SEM, CLSM, XRPD and DSC, and the in vitro drug release was tested using a paddle method. SEM and CLSM observation showed that the LBDDS was efficiently distributed throughout the pores of the silica. The results of DSC and XRPD illustrated that the lipid existed inside the silica at amorphous state. The drug-loaded SLH showed good flowability, compressibility, compactibilty and two-phase in vitro drug release process within 24 hours, which did not change obviously even after storage at 40 °C for 10 d.The present study provided a novel and simple method to prepare tacrolimus sustained release powder, which provided a feasible solution to solidify the liquid LBDDS of not only extended drug release behavior, but also improved stability and micromeritic properties.

Characteristics and pharmacokinetics of tripterygium glycosides nano-carries transdermal delivery systems:skin-blood synchronous microdialysis and numerical simulation

The traditional Chinese medicine tripterygium glycosides(TPG)is used clinically to treat some Rheumatism,Eczema,immunosuppression and tumor,with the activities of hypnosis,antipyretic,analgesic,antiinflammatory,allergy and antitumor.However TPG has low water solubility and low skin permeability,so its clinical use is limited.Transdermal delivery systems can provide a controlled drug release rate that can keep constant concentrations of drug in the plasma for up to multiple days,improved patient compliance,and the possibility ofreducing the rate and severity of side effects.In this study,a fast and sensitive technique skin-blood two sites synchronous microdialysis coupled with LC-MS was used to study the pharmacokinetic parameter of three different formulations(TPG nanoemulsion,TPG nanoemulsion based gels and TPG gel).Creating a multilayer model,use the model to simulate the three formulations dynamics in transdermal-drug delivery system.The experiment results showed that the TPG nanoemulsion,TPG nanoemulsion based gels can significantly raise the drug concentrations in skin more than that of TPG gels.The numerical simulation results indicating that TPG gel and TPG nanoemulsion are close to practical measurements,only in the concentration increase phase the numerical simulation result has some difference with the experimental results.TPG nanoemulsion based gels have significant difference with the experimental results,both in concentration increase stage and concentration decreasing stage,but its trend was same.The study shows that the skin-blood synchronous microdialysis technique provided a new method for the pharmacokinetics study of nanocarriers transdermal delivery systems.In addition,the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery system.

Process Modeling of Ferrofluids Flow for Magnetic Targeting Drug Delivery

Among the proposed techniques for delivering drugs to specific sites within the human body, magnetic targeting drug delivery surpasses due to its non-invasive character and its high targeting efficiency. Although there have been some analyses theoretically for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel of human body. This paper presents a mathematical model to describe the hydrodynamics of ferrofluids as drug carriers flowing in a blood vessel under the applied magnetic field. A 3D flow field of magnetic particles in a blood vessel model is numerically simulated in order to further understand clinical application of magnetic targeting drug delivery. Simulation results show that magnetic nanoparticles can be enriched in a target region depending on the applied magnetic field intensity. Magnetic resonance imaging confirms the enrichment of ferrofluids in a desired body tissue of Sprague-Dawley rats. The simulation results coincide with those animal experiments. Results of the analysis provide the important information and can suggest strategies for improving delivery in favor of the clinical application.

Research progress of triptolide-loaded nanoparticles delivery systems

This paper reviewed the study of triptolide-loaded nano delivery systems (NDOS) in our group during the past. It was investigated for the preparation, characterization, pharmacology and toxicology of solid lipid nanoparticles (SLN), microemulsion and polymeric nanoparticles. The results indicated that the NDS presented more powerful activity and a lower toxicity in comparison with other drug carrier.

Recent advances in endogenous and exogenous stimuli-responsive nanoplatforms for bacterial infection treatment

As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,targeted or longer half-life characteristics,also plays an important role in improving the therapeutic effect and reducing the toxic side effects of conventional drugs.Despite its potential benefits,the traditional nanomedical drug delivery system has some practical limitations,including incomplete and slow drug release,as well as insufficient accumulation at infection sites.Stimuli responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles,which can provide several advantages like:enhancing the pharmacokinetics and biodistribution of antimicrobial drugs,increasing their effective bioavailability,reducing their dosage frequency,and improving their antimicrobial efficacy against biofilm-related infections,while slowing down the development of antimicrobial resistance,which is expected to trigger a medical revolution in the field of human health,thus bringing huge clinical benefits.In this review,we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area.Using specific infectious microenvironments(pH,enzymes,reactive oxygen species and toxins),this review systematically presents the design principles of nano delivery systems and the mechanisms by which endogenous stimuli induce changes in the morphology or properties of delivery systems to achieve programmed drug release.Furthermore,exogenous stimuli such as light,heat,and magnetic fields can also control the release of drugs.Last but not least,we discussed the challenges and opportunities for future clinical translation of stimuli-responsive nanoplatforms in bacterial infections.

基于中药单体构建的环境响应型纳米递药系统在肿瘤治疗中的研究进展

中药单体对肿瘤具有一定的疗效,但其低靶向性、难以在肿瘤部位聚集等不足限制了其应用。环境响应型纳米递药系统作为一种新型药物递送方式,具有靶向性递药、减少药物毒副作用、环境响应性释放等优势,在肿瘤治疗中得到广泛应用。该文通过查阅并整理相关文献,从中药单体治疗肿瘤的概况、环境响应型中药单体纳米递药系统的分类以及其在肿瘤治疗中的应用3个方面进行概括总结,旨在为解决中药单体治疗肿瘤的局限性提供思路。

一种氟化纳米给药系统通过抑制阿霉素外排逆转MCF-7/ADR细胞耐药性的研究

目的通过合成氟化纳米材料完成对阿霉素(doxorubicin,dox)的高效负载,并实现纳米药物对抗肿瘤耐药的机制研究。方法评估不同氟化程度(PF4和PF8)的纳米药物(nano dox)的理化性能,筛选出更为优良的氟化nano dox;通过细胞毒性、细胞摄取、凋亡以及对抗外排泵P-糖蛋白(P-glycoprotein,P-gp)的研究,考察nano dox对抗肿瘤多药耐药以及体外抗肿瘤活性研究。结果通过考察各种理化指标,PF8相对于PF4显示出更优良的负载dox性能;通过细胞毒性实验证明,nano dox的IC 50值只有游离dox IC 50值的1/40,显示出nano dox在对抗耐药性方面优良的体外活性;细胞摄取和凋亡研究说明nano dox可以有效提高耐药MCF-7/ADR细胞对dox的摄取并能成功地进入细胞核内,最终导致凋亡诱导的抗癌活性;P-gp的药物外排研究说明nano dox可以有效绕过P-gp外排泵,达到增加耐药细胞对药物的摄取同时减少外排量的双重作用。结论通过氟化nano dox的设计可以有效绕过P-gp对药物的外排作用,增加药物在耐药肿瘤细胞内的摄取,减少其外排,从而达到有效的对抗肿瘤多药耐药效果。

纳米技术在骨质疏松症治疗中的研究进展

目的 总结纳米技术在骨质疏松症治疗中的研究进展,展望其在临床上的应用前景。方法 应用计算机检索Pubmed、中国期刊全文数据库(CNKI)中2006-2023年的相关文献。在标题、摘要、关键词中以“nano, osteoporosis, bone marrow mesenchymal stem cells(BMMSCs),treatment”或“纳米,骨质疏松,骨髓间充质干细胞,治疗”为检索词进行检索。选择与纳米技术治疗骨质疏松症密切相关的文章,优先选择时间最近且发表于权威杂志的文章。结果 对筛选到的文献进行精选得到34篇文献进行综述。结论 纳米技术由于其高靶向性、高利用率和低不良反应的特性,在骨质疏松症的治疗研究中备受关注。目前常用的纳米技术包括药物纳米化和纳米载药两大类。但目前纳米技术尚未在临床上应用于骨质疏松症的治疗,仍有许多问题待解决。

治疗肺部疾病的中药活性成分可吸入纳米给药系统研究进展

肺部给药能直接将药物运送至肺部,是肺部疾病的优选给药方式。中药活性成分如槲皮素、紫杉醇等对肺部疾病具有良好的治疗效果,但其存在水溶性差和肺清除率高等问题。将中药活性成分负载在纳米给药系统中,可提高药物的水溶性、稳定性及其在肺部的渗透性和滞留性。基于此,本研究综述了治疗肺部疾病的中药活性成分可吸入纳米给药系统的研究进展,发现有基于壳聚糖、脂质(包括脂质体、固体脂质纳米粒、纳米结构脂质载体)、靶向配体(包括靶向叶酸受体、靶向转铁蛋白受体、外泌体)的中药活性成分可吸入纳米给药系统,这些纳米给药系统综合考虑了粒径、表面电荷和疏水性等关键因素,可避免药物被黏液、纤毛和巨噬细胞清除,具有较好的应用潜力。

刺激响应型纳米载体的设计和研究进展

刺激响应型纳米载体主要包括内源性、外源性、双重和多重刺激响应型纳米载体等。内源性刺激响应型纳米载体的设计主要基于肿瘤组织和健康组织之间存在的一些内在生理学显著差异;外源性刺激响应型纳米载体的设计,通常会采用远程装置,具有靶点特异性和药物时-空可控释放的优点;双重和多重刺激响应型纳米载体与单刺激响应型纳米载体相比,具有多功能协同功效的优点。本文主要综述了内源性、外源性、双重和多重刺激响应型纳米载体的设计和研究进展,并对其在肿瘤治疗中的应用前景进行了展望。

影响姜黄素口服吸收的因素及药物递送策略

姜黄素是一类存在于姜黄根茎中的脂溶性多酚类化合物,具有抗氧化、抗炎、抗纤维化、抗肿瘤、抗菌、抗病毒等多种药理作用。由于姜黄素的水溶性低、化学稳定性差和首关效应强等因素导致口服吸收效果差,阻碍了其临床应用。增加姜黄素的口服生物利用度的策略包括加入代谢酶抑制剂或P-糖蛋白(P-gp)抑制剂,或者采用纳米药物递送系统。该文综述影响姜黄素口服吸收的关键因素及相关药物递送策略,建议对姜黄素纳米制剂的设计和工业化进行更深入研究;选择兼具P-gp和CYP酶抑制活性的药用辅料递送药物;对于药物浓度需求较高的治疗,靶向递送或皮肤局部给药使药物精确作用于病变部位可能更合理;基于药动学和药效学方面的协同作用进行药物联用。

硬脂酸改性纳米递送系统递送药物的研究进展

近年来,纳米技术在生物医学中的应用发展迅猛,尤其在药物递送领域取得了巨大进展。基于纳米材料开发的新型纳米递送系统具有提高药物生物利用度和降低药物不良反应等优点,在生物医药领域具有重要的应用价值。作为一种天然的脂肪酸,硬脂酸具有提高药物肿瘤靶向和抗酸降解等多重作用,硬脂酸的接枝修饰可有效提高难溶性药物生物利用度,在药物治疗方面具有广泛的应用前景。对硬脂酸修饰纳米递送系统材料在靶向肿瘤、神经系统疾病和炎症疾病治疗等方面的研究进行总结,以期为纳米递送系统在药物治疗的深入研究和应用提供参考。

多载药纳米递药系统用于提高多西紫杉醇抗肿瘤疗效的研究进展

目的对多西紫杉醇与其他抗癌药物共载药纳米递药系统在肿瘤治疗中的作用机制进行综述,旨在为以多西紫杉醇为代表的化疗药物共载药纳米递药系统研究提供一定的参考。方法以“多西紫杉醇”、“联合治疗”、“纳米递药系统”、“肿瘤”等检索词对国内外文献进行查阅,总结多西紫杉醇与其他药物共载药纳米递药系统对肿瘤的治疗效果,并对其治疗机制进行归纳。结果多西紫杉醇属于典型的紫杉烷类抗肿瘤药物,在临床中,多西紫杉醇对多种恶性肿瘤具有显著的治疗效果。然而,现有多西紫杉醇注射剂由于其组织特异性差、使用有机溶剂增溶、易产生耐药性等原因,一定程度上影响其抗肿瘤疗效的发挥及产生一定的不良反应。将其他药物与多西紫杉醇联用是提高多西紫杉醇抗肿瘤效果、克服其耐药性和减少其不良反应的一种有效方法。然而,将多种药物简单物理混合所构建的制剂尚不能解决多西紫杉醇制剂现有的缺陷;而借助于纳米递药系统,可以有效克服以上缺陷。结论今后应深度挖掘纳米递药系统在共载抗肿瘤药物递送方面的意义,促使以多西紫杉醇为代表的化疗药物共载药在肿瘤治疗方面取得更大的进展。

原位自组装纳米递药系统用于肿瘤免疫治疗的研究进展

目的对原位自组装纳米递药系统的构建及其在肿瘤免疫治疗中的作用机制进行综述,旨在为基于肿瘤免疫治疗的药物递送提供新的思路。方法以“原位自组装”、“免疫治疗”、“肿瘤”等检索词对国内外文献进行查阅,总结自组装纳米递药系统在肿瘤部位的构建情况,并对其增强免疫疗效的机制进行归纳。结果原位自组装纳米递药系统能够通过体外辅助靶向到达病灶部位,在疏水相互作用、静电作用、配位键等多种作用力的驱动下,触发体外刺激或体内生理病理环境刺激进而原位自组装形成新的物质。该策略能够通过增加免疫药物滞留、提高肿瘤免疫原性、促进抗原呈递细胞的成熟以及增加免疫效应细胞浸润来增强机体免疫,综合提高免疫效力。结论今后应深度挖掘原位自组装纳米药物在抗肿瘤药物递送方面的意义,促使自组装药物在肿瘤治疗方面取得更大的进展。

纳米药物递送系统用于炎症性肠病治疗的研究进展

炎症性肠病(inflammatory bowel disease,IBD)是一种反复发作的慢性非特异性肠道炎性疾病,主要分为溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn disease,CD)两种主要形式。其致病原因十分复杂,目前普遍认为遗传因素、免疫系统的异常激活、环境因素以及肠道微生物群的失调都可能对IBD的发病起到重要作用,且伴随多种并发症,还会增加患结直肠癌(colorectal cancer,CRC)的风险。目前临床治疗主要以预防复发和延缓炎症发展为目的,缺乏更加有效的治疗手段。近年来,随着IBD研究的深入,纳米药物递送系统(nano drugs delivery systems,NDDS)的发展,许多纳米药物被开发用于IBD治疗。本综述系统总结了IBD发病诱因、NDDS治疗IBD的优势及其在IBD治疗中的应用,为开发有前途的精准医疗纳米平台提供理论指导。

甘草酸、姜黄素和羟基喜树碱自组装纳米粒递药系统的工艺优化研究

目的:以两亲性药物分子甘草酸(GA)、疏水性药物姜黄素(CUR)和羟基喜树碱(HCPT)为材料,通过自组装形式构建GA、CUR和HCPT纳米粒递药系统(GA/CUR/HCPT-NPs),考察其制备工艺并进行质量评价。方法:采用反溶剂沉淀法和透析法相结合制备GA/CUR/HCPT-NPs,利用响应面Box-Behnken法对制备工艺进行优化,最终获得尺寸合适,稳定电荷,高载药量的GA/CUR/HCPT-NPs;并对优化出来的GA/CUR/HCPT-NPs进行核磁共振氢谱(1HNMR)、差示扫描量热法(DSC)、高分辨X射线衍射法(XRD)、傅里叶红外分光光度法(FTIR)、紫外分光光度法(UV)等表征和微观形态观察,并测定GA/CUR/HCPT-NPs中GA、CUR和HCPT含量大小。结果:得到的最优处方为去离子水体积30 mL,二甲基亚砜(DMSO)1 min内滴入去离子水,制备温度为40℃,确定GA、CUR、HCPT投药量分别为6.00 mg、10.03 mg、5.01 mg;测量GA/CUR/HCPT-NPs粒径为(146.37±0.15)nm,且带较高的稳定电荷-(34.43±0.77)mV,PDI为0.157±0.01,透射电子显微镜(TEM)和扫描电子显微镜(SEM)可观察到GA/CUR/HCPT-NPs是类球形或球形,并且均匀分布;1HNMR、DSC、XRD等证明了成功自组装成稳定的GA/CUR/HCPT-NPs,并且在7 d内4℃保存条件下稳定性良好;高效液相色谱(HPLC)测定GA/CUR/HCPT-NPs中GA、CUR、HCPT的载药量分别为57.19%、39.17%和3.07%。结论:本研究通过优化的反溶剂沉淀法结合透析法成功制备尺寸合适、均匀分布的GA/CUR/HCPT-NPs,为进一步实验奠定了基础。

小分子纯药自组装递药系统用于抗肿瘤的研究进展

近年来,纳米技术在抗肿瘤小分子药物递送方面显示出巨大潜力。然而,大部分基于载体的纳米递药系统都存在载药量低、制备工艺复杂、载体具有毒性和免疫原性等问题,阻碍了纳米制剂的临床转化。自组装技术的出现为此开辟了一条新途径,其中由小分子药物自组装得到的纯药递送系统引起了研究者们的广泛关注。小分子纯药自组装递药系统制备工艺简单、载药量高、毒性低,具有可调式的分子结构,更强的药物保留性、生物相容性、可降解性以及更高的患者依从性,在抗肿瘤领域的应用愈加广泛,具有良好的临床转化前景。本综述在肿瘤治疗的背景下,梳理和介绍了小分子纯药自组装递药系统的原理、分类、制备方法(传统及新型)等方面的研究进展,并重点分析了单一纯药自组装递药系统和多药共组装递药系统在化疗、光疗、免疫治疗以及联合治疗中的最新应用进展,旨在探讨小分子纯药自组装递药系统在抗肿瘤治疗方面的发展潜力以及临床转化前景,为进一步优化小分子纯药自组装纳米递药系统并拓展其在抗肿瘤领域的应用提供研究思路。