Characteristics and Transdermal Drug Delivery of Triamcinolone-Acetonide-Acetate-Loaded Solid Lipid Nanoparticles Carbomer Gel

Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.

Recent advances in arsenic trioxide encapsulated nanoparticles as drug delivery agents to solid cancers

Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago,its anti-cancer properties for various malignancies have been under intense investigation.However,the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers.This is due to arsenic＇s rapid clearance by the body＇s immune system before reaching the tumor site.Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success.This review summarizes the past and current utilization of arsenic trioxide in the medical field with primary focus on the implementation of nanotechnology for arsenic trioxide delivery to solid cancer cells.Different approaches that have been employed to increase arsenic＇s efficacy,specificity and bioavailability to solid cancer cells were evaluated and compared.The potential of combining different approaches or tailoring delivery vehicles to target specific types of solid cancers according to individual cancer characteristics and arsenic chemistry is proposed and discussed.

Preparation and evaluation of alpha-mangostin solid self-emulsifying drug delivery system

Alpha-mangostin(AMG),a natural xanthone extracted from Garcinia mangostana Linn,has a variety of pharmacological therapeutic effects such as antioxidant activity,antibacterial activity,anticancer,and anti-inflammatory[1].However,it has poor aqueous-solubility and dissolution,which results in low bioavailability.Solid self-emulsifying drug delivery system(solid-SEDDS),an effective pharmaceutical strategy,offers the potential for enhancing the oral bioavailability of poorly water-soluble drugs[2].Therefore,solid-SEDDS is of interest as a potential method for enhancing the solubility and dissolution of AMG.

Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-microemulsifying drug delivery systems

The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of SMEDDS.Through the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the SMEDDS.Therefore, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.

Inhibitive Effect of Cremophor RH40 or Tween 80-based Self-microemulsiflying Drug Delivery System on Cytochrome P450 3A Enzymes in Murine Hepatocytes

This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.

脂质纳米粒在经皮给药系统中治疗皮肤病的应用

经皮给药作为一种非侵入性给药方式,正逐渐受到广大医药工作者和患者的青睐。然而,皮肤角质层的屏障功能限制了药物的经皮吸收。脂质纳米粒作为一种新型的药物载体能够有效提高皮肤渗透性、减少药物相关副作用。本文就脂质纳米粒的特点、透皮作用机制以及在多种皮肤病中的应用做一综述,阐明脂质纳米粒在经皮给药领域的广阔发展前景,为脂质纳米粒的开发及临床应用提供参考。

Effect of mesopores on solidification of sirolimus self-microemulsifying drug delivery system

To investigate the influence of mesopores towards the solidification of self-microemulsifying drug delivery system(SMEDDS), mesoporous silica nanospheres(MSNs) and Santa Barbara Amorphous-15(SBA-15) were compared. The MSNs had hydrodynamic size of 195.35 ± 5.82 nm, and pore diameter of 2.70 nm. The SBA-15 had hydrodynamic size of 2312.19 ± 106.93 nm, and pore diameter of 10.91 nm. The MSNs and SBA-15 showed similar loading efficiency of SMEDDS containing sirolimus(SRL). However,MSNs had higher drug dissolution and in vivo absorption, with relative bioavailability of 174.62%. Thus,the length of mesopores played a more important role in solidification of SMEDDS as compared with the pore diameter. This study suggests that the SMEDDS-MSNs can be a potential candidate for oral administration of hydrophobic drugs.

微针技术在经皮给药系统中应用的研究进展

微针在研发初期主要用于药物的输送,可以克服传统经皮给药的局限性,是继口服和注射之后的一种给药新途径。介绍了微针的类型及其释药机制,阐述了固体、涂层、空心、溶解、水凝胶5种类型微针的给药方式的优缺点及其在经皮给药领域中应用的最新研究进展。说明了不同的微针类型适用于不同性质的药物输送,当前先进的微针经皮给药系统可以显著提高药物经皮的渗透量,达到良好的治疗效果。此外,还对微针在当前发展中可能存在的问题进行了探讨,并对其在未来的发展前景进行了展望。

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.

In vitro and in vivo evaluation of a self-microemulsifying drug delivery system for silybin

To enhance the oral absorption of the poorly water-soluble drug silybin, a self-microemulsifying drug delivery system （SMEDDS） composed of ethyl linoleate, Cremophor EL and PEG 400 for oral administration of silybin was formulated, and its physicochemical properties and bioavailability of silybin were evaluated. The in vitro release of silybin from microemulsion and dispersion of silybin from SMEDDS were significantly faster than those from the commercial silybin hard capsule, respectively. The area under the drug concentration-time curve （AUC） and the mean maximum plasma level （Cmax） of the SMEDDS were remarkably greater than those of the hard capsule after oral administration to rats. The absorption of silybin formulated in SMEDDS exhibited a 2.3-fold increase in bioavailability as compared with the hard capsule. These results demonstrated that SMESDDS might be a useful drug delivery system for the oral delivery of the poorly water-soluble drug silybin.

固体自微乳药物递送系统的研究进展

作为一种新型的药物递送系统,固体自微乳药物递送系统可以显著提高水难溶性药物的口服生物利用度,且具有液态自微乳和固体制剂二者的优势。通过设计不同的辅料处方和包衣技术,可以控制药物释放使其具有靶向性,来达到不同的给药目的。固体自微乳药物递送系统的应用前景广阔,具有研究意义。本文对固体自微乳载体、固化技术、固体自微乳新制剂的应用进行了总结归纳,为提高水难溶性药物释放的固体自微乳化技术的研究提供了参考。

弓形虫病治疗:从传统药物到纳米药物

刚地弓形虫(Toxoplasma gondii)是一种呈世界性分布的机会致病原虫,几乎感染所有的温血动物,引起人兽共患弓形虫病。免疫力正常的个体感染常呈隐性感染,无明显的临床症状;但免疫功能缺陷的人或动物感染则会导致严重后果,需进行有效治疗。目前,弓形虫病已是全世界绵羊和山羊流产的常见原因,该病给人类健康和畜牧业生产都造成了严重影响。因此,控制人和动物弓形虫病对公共卫生和畜牧业经济发展极为重要。以往用于弓形虫病治疗的药物,由于其副作用和/或疾病分期的特点,治疗效果大大受限,然而纳米药物可有效克服传统药物的局限性。本文就纳米技术在弓形虫病治疗方面的新进展作一综述,以期为抗弓形虫病药物的研究提供新思路。

载体-抑晶剂多元体系过饱和环孢素固体分散体的制备及体外溶出研究

目的 制备载体-抑晶剂多元体系过饱和环孢素固体分散体,并对其进行体外溶出研究。方法 采用热熔挤出技术,分别以HME专用辅料AFFINISOL HPMC 15LV、HPMC 100LV、聚乙烯吡咯烷酮VA64为载体,泊洛沙姆188、羟丙甲纤维素(HPMC E5)、聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)为抑晶辅料,制备单元及多元体系固体分散体。利用粉未X射线衍射法(PXRD)与差示扫描量热法(DSC)对其进行物相表征,并通过体外模拟过饱和溶出试验对聚合物的过饱和增溶能力、抑晶剂的抑晶效果进行考察。结果 结果表明,HPMC 100LV型号聚合物在过饱和增溶上具有较强优势。析晶抑制能力表现为泊洛沙姆188> HPMC E5> Soluplus,且抑晶剂联合用量在药物的0.5倍时抑晶效果最优。结论本研究构建了载体-抑晶剂多元体系固体分散体,可为进一步解决难溶性药物在胃肠道析出及过饱和释药系统的开发提供理论指导。

Recent advances in drug delivery applications of cubosomes,hexosomes,and solid lipid nanoparticles

The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.

固体脂质纳米粒作为药物载体

固体脂质纳米粒是一种新型的纳米给药系统。本文综述了固体脂质纳米粒作为药物载体的研究进展,包括固体脂质纳米粒的组分选择、制备方法、表面修饰,并且对物化性质分析、给药途径以及载药和释放进行了讨论。

固体脂质纳米粒的研究进展

目的综述固体脂质纳米粒的最新研究进展。方法以国内外大量有代表性的论文为依据,将固体脂质纳米粒的制备方法、特性分析、药物载入、药物释放及应用情况进行了概括,指出了发展前景和尚待解决的问题。结果固体脂质纳米粒的多种制备方法各有优、缺点,调整制备参数可调整药物的包封率和释药曲线。结论固体脂质纳米粒可供多途径给药,是极有发展前景的新型给药系统。

经内耳途径靶向脑给药的初步研究

本文探寻经内耳途径输送药物到脑部的可行性,为脑靶向给药提供一条崭新的研究思路。制备醋酸地塞米松(DA)固体脂质纳米粒(SLN),建立相应的HPLC含量测定方法。经静脉和鼓室注射DA-SLN,并与地塞米松磷酸钠(DSP)溶液相比较,测定药物在脑脊液(CSF)和内耳外淋巴液(PL)中的浓度及药代动力学参数。结果表明,与静脉注射比较,鼓室注射药物在CSF的局部生物利用度显著提高,鼓室注射DA-SLN比静脉注射高2.5倍,鼓室注射DSP溶液比静脉注射高4.3倍。与DSP溶液比较,鼓室注射DA-SLN能明显增加进入CSF的药量和延长药物的作用时间,AUC和MRT分别较前者高13和19倍;并且药物在PL中分布减少,其AUC低76%。提示经内耳途径给药有望成为一种新的脑靶向方法,值得进一步研究。

肝靶向氟尿嘧啶类脂纳米粒的研究

目的 为了提高氟尿嘧啶 (5 Fu)的疗效 ,降低其毒副作用 ,制备具肝靶向的 5 Fu类脂纳米粒。方法 利用氟尿嘧啶与硬脂酰氯进行反应 ,制备了 5 Fu前体药物N1 硬脂酰 5 Fu ,通过红外光谱及核磁共振谱对合成的目标化合物进行结构确认。同时研究了前体药物的性质及稳定性。采用物理凝聚法制备类脂纳米粒 ,并研究其形态、粒径及粒径分布、载药量、体外释药特征、动物体内分布与药代动力学参数等。结果 平均粒径dav=2 40 19nm ,载药量为 2 0 5 3 %。体外释药速率符合一级动力学模型。与 5 Fu水针剂比较 ,类脂纳米粒组在肝脏中药物含量平均增加了一倍以上。家兔体内主要药动学参数为 :Vc=0 0 4336L·kg-1,T1/ 2 β =1 2 834h ,CL =0 16 32L·h-1。结论 利用前体药物可提高药物的脂溶性 ,首次以物理凝聚法制备类脂纳米粒 ,小鼠体内分布研究表明类脂纳米粒有明显的肝靶向 。