Formulation of the novel structure curcumin derivative–loaded solid lipid nanoparticles: synthesis,optimization, characterization and anti-tumor activity screening in vitro

This study investigated the effect of structural modification of Curcumin (CU) combined with the solid lipid nanoparticles (SLN) drug delivery system on anti-tumor activity in vitro. A new structure of Curcumin derivative (CU1) was successfully synthesized by modifying the phenolic hydroxyl group of CU. CU1 was two times more stable than CU at 45 °C or constant light. The SLN containing CU1 (CU1-SLN) was prepared, and the particle size, polydispersity index, entrapment efficiency, drug loading, and zeta potential of CU1-SLN were (104.1 ± 2.43) nm, 0.22 ± 0.008, (95.1 ± 0.38) %, (4.28 ± 0.02) %, and (28.3 ± 1.60) mV, respectively. X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) showed that CU1 is amorphous in SLN. CU1-SLN released the drug slowly for 48 h, while CU and CU1 were released rapidly within 8 h. In terms of cytotoxicity, CU1 exhibited a 1.5-fold higher inhibition than CU against A549 and SMMC-7721 cells, while CU1-SLN showed 2-fold higher inhibition than CU1. Both CU1 and CU1-SLN reduced the toxicity in normal hepatocytes compared with CU (2.6-fold and 12.9-fold, respectively). CU1-SLN showed a significant apoptotic effect (p < 0.05). In summary, CU1 retained the inhibitory effect of CU against tumor cells, while improving stability and safety. Additionally, CU1-SLN presents a promising strategy for the treatment of liver and lung cancer.     

固体脂质纳米粒和纳米结构脂质载体在经皮给药系统中的研究进展

目的介绍固体脂质纳米粒和纳米结构脂质载体在经皮给药系统中的应用与优势,为其开发利用提供参考。方法查阅国内外相关文献共30余篇,从固体脂质纳米粒和纳米结构脂质载体用于经皮给药系统的优势、药物在固体脂质纳米粒和纳米结构脂质载体中的分布形式及固体脂质纳米粒和纳米结构脂质载体在经皮给药领域中的应用等方面进行综述。结果固体脂质纳米粒和纳米结构脂质载体可以增强药物稳定性,能在皮肤表面产生包封效应,增加皮肤水合作用,具有药物靶向性。结论固体脂质纳米粒和纳米结构脂质载体是极有发展前景的新型经皮给药系统。     

Stability study of sodium colistimethate-loaded lipid nanoparticles

In the last decades, the encapsulation of antibiotics into nanoparticulate carriers has gained increasing attention for the treatment of infectious diseases. Sodium colistimethate-loaded solid lipid nanoparticles (Colist-SLNs) and nanostructured lipid carriers (Colist-NLCs) were designed aiming to treat the pulmonary infection associated to cystic fibrosis patients. The nanoparticles were freeze-dried using trehalose as cryoprotectant. The stability of both nanoparticles was analysed over one year according to the International Conference of Harmonisation (ICH) guidelines by determining the minimum inhibitory concentration (MIC) against clinically isolated Pseudomonas aeruginosa strains and by studying their physico-chemical characteristics. The results showed that Colist-SLNs lost their antimicrobial activity at the third month; on the contrary, the antibacterial activity of Colist-NLCs was maintained throughout the study within an adequate range (MIC ≤16?μg/mL). In addition, Colist-NLCs exhibited suitable physico-chemical properties at 5?°C and 25?°C/60% relative humidity over one year. Altogether, Colist-NLCs proved to have better stability than Colist-SLNs.     

氟尿苷二丁酸酯固体脂质纳米粒的制备和肝靶向性研究

采用薄膜-超声分散法制备氟尿苷二丁酸酯(FUDRB)固体脂质纳米粒(FUDRB-SLN)和半乳糖苷(G₂)修饰的FUDRB-SLN(FUDRB-G₂SLN)。透射电镜研究其形态及粒径分布；凝胶色谱法测定载药量、包封率。结果表明，FUDRB-SLN和FUDRB-G₂SLN的粒径分别为(137.5±11.1)nm和(95.0±10.7)nm，载药量分别为9.64%和8.56%，包封率分别为99.81%和96.23%。为比较其肝靶向作用，小鼠尾静脉给药后，HPLC法测定氟尿苷(FUDR)在血清及肝、 肾、 肺匀浆中的浓度，计算出FUDR-sol、 FUDRB-SLN和FUDRB-G₂SLN的肝靶向效率分别为2.56、 5.90和8.28。FUDRB-G₂SLN组480 min时在肝脏中仍可检测到FUDR。这些结果说明FUDRB-SLN和FUDRB-G₂SLN在小鼠体内具有良好的肝靶向性，G₂修饰的SLN是一种良好的药物载体，可使药物选择性地导向肝细胞，且具有缓释作用。     

氟尿嘧啶及其类脂纳米粒在兔体内药物动力学的比较

目的 :研究氟尿嘧啶及其类脂纳米粒在兔体内的药物动力学。方法 :血样经乙酸乙酯萃取后 ,分别在 Shim pack CL C-ODS(5︼m,15 0 mm× 4.6 m m)色谱柱上分离 ,以乙睛 -水 (30∶ 70 )作为流动相 ,在 2 6 5 nm处检测 ,所得血药数据用 3P87程序拟合并估算药物动力学参数。结果 :氟尿嘧啶及其类脂纳米粒体内过程均符合二室开放模型 ,主要药物动力学参数为 :T1 / 2α分别为 0 .16 2和 0 .0 80 7h,T1 / 2β分别为 6 .980和 1.2 83h,CL(s)分别为 0 .818和 0 .16 3 3L/h。结论 :氟尿嘧啶与其类脂纳米粒体内主要药物动力学参数有显著的差异 ,提示氟尿嘧啶制备成胶体微粒制剂可改变其体内药物动力学行为     

VitD3-loaded solid lipid nanoparticles: stability,cytotoxicity and cytokine levels

Vitamin D3 (VitD3) has several beneficial effects on many metabolic pathways such as immunity system, bone development. The aim of the study, encapsulation of VitD3 with solid lipids, determine encapsulation efficiency and biocompatibility of nanoparticles. Therefore, VitD3-loaded solid lipid nanoparticles (SLNPs) were developed by optimising ratios of VitD3, stearic acid, beeswax and sodium dodecyl sulphate (SDS). Thermal stability, degradation profile, crystallinity rate, encapsulation efficiency and release profile of SLNPs were determined. Cytotoxicity of SLNPs on HaCaT, L929 and HUVEC cells were investigated. Negatively charged and VitD3-loaded nanoparticles with diameters between 30 and 60?nm were obtained. SLNPs containing up to 5.1?mg VitD3 per 10?mg powder samples were obtained. Cell proliferations were stimulated after exposure with VitD3-loaded SLNPs. Besides, inflammatory response after exposure to VitD3-loaded SLNPs was evaluated via determining IL10 and TNF-alpha levels on THP-1 cells. According to the results, no inflammatory response was observed.     

芹菜素固体脂质纳米粒的制备

目的为芹菜素新型制剂的研究和开发提供实验基础。方法采用热熔超声法制备芹菜素固体脂质纳米粒;以包封率为指标,通过正交试验对处方进行优化。结果制备的纳米粒为类球形,包封率为63.11%,平均粒径为(135±18)nm,zeta电位为-18.90 mV,36 h体外累积释放95.74%。结论热熔超声法可用于制备芹菜素固体脂质纳米粒。     

紫杉醇固体脂质纳米粒大鼠体内药动学

目的研究紫杉醇固体脂质纳米粒在大鼠体内的药动学。方法10只健康大鼠,雌雄各半,分为2组,分别口服给药紫杉醇固体脂质纳米粒和紫杉醇乳剂30 mg.kg-1,在设计的时间点从颈静脉取血,采用RP-HPLC测定紫杉醇在全血中的药物浓度,药动学参数用3P97软件进行处理。结果大鼠口服给药后,紫杉醇固体脂质纳米粒和乳剂的tm ax分别为3.133 h和1.627 h,MRT分别为10.362 h和3.297 h,mρax分别为1.512 2 mg.L-1和0.718 9 mg.L-1。结论固体脂质纳米粒能够显著改善大鼠体内紫杉醇的药动学行为,有利于其更好地发挥抗肿瘤作用。     

蟾酥固体脂质纳米粒冻干工艺及其表征

目的 研究了蟾酥固体脂质纳米粒冻干剂的工艺及表征。方法以外观、色泽、再分散性为指标，考察了不同工艺条件对蟾酥固体脂质纳米粒冻干剂重建的影响，对冻干工艺参数进行了优化，并对蟾酥固体脂质纳米粒冻干剂进行了研究。结果5％乳糖和5％葡萄糖显示了优良的保护作用和再分散性，优化的冻干工艺为：-45℃预冻10h，升温至-30℃维持6h，再升温至-10℃维持3h，再升温至0℃维持2h，最后升温至25℃维持3h。结论通过支架剂的筛选和优化冻干工艺参数可以获得稳定的固体脂质纳米粒冻干剂。     

注射用葫芦素B固体脂质纳米粒的制备

目的为提高葫芦素B的疗效,降低毒性及不良反应,,制备了葫芦素B固体脂质纳米粒。方法采用高压匀质法制备葫芦素B固体脂质纳米粒。以单因素轮换法考察影响制备葫芦素B固体脂质纳米粒的处方和工艺因素,通过正交设计优化处方。结果制备的纳米粒为类球形纳米粒子,包封率质量分数为90.67%,平均粒径为135 nm。结论高压匀质法可用于制备葫芦素B固体脂质纳米粒。     

长春西汀固体脂质纳米粒的制备及其性质考察

目的制备长春西汀固体脂质纳米粒,为长春西汀新型给药系统的开发与应用提供实验基础。方法以长春西汀为模型药物、山嵛酸甘油酯为载体材料,采用热熔超声法制备长春西汀固体脂质纳米粒,并通过正交试验设计对处方进行优化。以包封率为评价指标,对其形态、体外释放度、短期稳定性等性质进行了考察。结果制备的纳米粒为球形及类球形,粒径为152.3 nm,包封率为93.68%,72 h体外累积释放71.84%,4℃下放置2个月稳定。结论热熔超声法可用于制备长春西汀固体脂质纳米粒,该纳米粒具有明显的缓释特征,可进一步进行体内释药行为的考察。     

雷公藤内酯醇固体脂质纳米粒的制备及理化性质

目的：以聚乙二醇单硬脂酸酯表面修饰材料结合到固体脂质纳米粒（solid lipid nanoparticles,SLN）,以雷公藤内酯醇（triptolide,TPL）为模型药,制备一种具有良好亲水亲脂性的雷公藤内酯醇固体脂质纳米粒。方法：采用熔融-乳化法制备固体脂质纳米粒。通过单因素考察、中心复合设计（central composite design,CCD）,考察脂质材料、聚山梨醇酯-80和PEG-stearate（PEG-SA）三个因素对TPL-SLN粒径、包封率和载药量的影响。通过透射电镜、热分析和X-射线衍射考察TPL-SLN的理化性质,并考察其固体脂质纳米粒的稳定性以及体外释放情况。用MTT法测定其对人正常肝L02细胞和肝癌细胞HepG2的增殖抑制作用并计算其IC₅₀。结果：最优的处方：脂质材料为7.5%,聚山梨醇酯80（Tween 80）为2%和PEG-SA为2%,其粒径（193.43±6.07）nm,包封率（87.63±0.09）%,载药量（0.33±0.01）%。透射电镜观察所制备的纳米粒的形态近似于球形,DSC分析和X-射线衍射证实TPL以非晶型的形式存在于固体脂质纳米粒中。稳定性考察发现纳米粒粒径在一个月的贮存期基本没有变化（P>0.05）,体外释放表明TPL-SLN具有体外缓释特性。TPL-SLN对肿瘤细胞的抑制作用强于正常肝细胞。结论：雷公藤内酯醇聚乙二醇修饰固体脂质纳米粒有望开发为临床口服用药新剂型。     

阿克拉霉素A固体脂质纳米粒冻干针剂在家兔体内药动学

目的:研究阿克拉霉素A固体脂质纳米粒(ACM-SLN)冻干针剂在家兔体内的药物动力学。方法:用RP-HPLC法测定家兔耳缘静注ACM-SLN冻干针剂和阿克拉霉素A(ACM-A)注射剂后不同时间血浆中ACM-A的浓度,绘制药-时曲线,计算药物动力学参数。结果:ACM-SLN冻干针剂和ACM-A注射剂的体内过程均符合二室模型,ACM-SLN冻干针剂的t1/2β与MRT显著延长,AUC增高,CL降低。结论:ACM-SLN冻干针剂有利于增加药物与肝脏肿瘤组织的接触时间,从而提高ACM-A的抗肝癌作用。     

Skin permeation of buprenorphine and its ester prodrugs from lipid nanoparticles: lipid emulsion,nanostructured lipid carriers and solid lipid nanoparticles

The aim of this study was to develop and characterize lipid nanoparticle systems for the transdermal delivery of buprenorphine and its prodrugs. A panel of three buprenorphine prodrugs with ester chains of various lengths was synthesized and characterized by solubility, capacity factor (log K′), partitioning between lipids and water and the ability to penetrate nude mouse skin. Colloidal systems made of squalene (lipid emulsion, LE), squalene + Precirol (nanostructured lipid carriers, NLC) and Precirol (solid lipid nanoparticles, SLN) as the lipid core material were prepared. Differential scanning calorimetry showed that the SLN had a more-ordered crystalline lattice in the inner matrix compared to the NLC. The particle size ranged from 220–300 nm, with NLC showing the smallest size. All prodrugs were highly lipophilic and chemically stable, but enzymatically unstable in skin homogenate and plasma. The in vitro permeation results exhibited a lower skin delivery of drug/prodrug with an increase in the alkyl chain length. SLN produced the highest drug/prodrug permeation, followed by the NLC and LE. A small inter-subject variation was also observed with SLN carriers. SLN with soybean phosphatidylcholine (SLN-PC) as the lipophilic emulsifier showed a higher drug/prodrug delivery across the skin compared to SLN with Myverol, a palmitinic acid monoglyceride. The in vitro permeation of the prodrugs occurred in a sustained manner for SLN-PC. The skin permeation of buprenorphine could be adjusted within a wide range by combining a prodrug strategy and lipid nanoparticles.     

Formulation of acyclovir-loaded solid lipid nanoparticles: design,optimization, and in-vitro characterization

The goal of this study was to design, optimize, and characterize Acyclovir-loaded solid lipid nanoparticles (ACV-SLNs) concerning particle size, zeta potential, entrapment efficiency, and release profile. Full factorial design (2³) was applied and the independent variables were surfactant type (Tween 80 and Pluronic F68), lipid type (Stearic acid and Compritol 888 ATO), and co-surfactant type (Lecithin and Sodium deoxycholate). The microemulsion technique was used followed by ultrasonication. The ACV-SLNs had a particle size range of about 172–542?nm. The polydispersity index (PDI) was found to be between 0.193 and 0.526. Zeta potential was in the range of –25.7 to –41.6?mV indicating good physical stability. Entrapment efficiency values were in the range of 56.3–80.7%. The drug release kinetics of the prepared formulations was best fitted to Higuchi diffusion model. After storing ACV-SLNs at refrigerated condition (5?±?3?°C) and room temperature (25?±?2?°C) for 4 weeks; we studied the change in the particle size, PDI, and zeta potential. The selected optimized formulation (F4) was containing Compritol, Pluronic F68, and Lecithin. These results indicated the successful application of this design to optimize the ACV-SLNs as a promising delivery system.     

Lipid nanoparticles: Different preparation techniques,characterization, hurdles,and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery

The bioavailability of an orally administered drug primarily depends on its solubility in the GIT and its permeability across cell membranes. Also, a drug in solution form is preferred for conducting pharmacological, toxicological and pharmacokinetic studies during the drug development stage. Thus, poor water solubility not only limits a drug’s biological application but also challenges its pharmaceutical development. The use of lipid nanoparticles (LNs) in pharmaceutical technology has been reported for several years due to its important in green chemistry for several reasons specifically for its biochemical as “green” materials and biochemical processes as green processes that can be very environmentally friendly. Also, the physiological/physiologically related lipids (GRAS) made LNs usually enhance the drug absorption in the GIT. Hence, the pathways for absorption, metabolism, and transportation are present in the body, which may contribute to a large extent to the bio-fate of the lipidic carrier. Moreover, the LNs improves the mucosal adhesion and increases their GIT residence time. The LNs with a solid matrix are two types: solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC). Also, their hydrophobic core provides a suitable environment for entrapment of hydrophobic drugs to improve its bioavailability. This review highlights and discusses the simple and easily scaled-up novel SLN and NLC along with their different production techniques, hurdles, and strategies for the production of LNs, characterization, lyophilization and drug release. Also, this review summarizes the research findings reported by the different researchers regarding the different method of preparation, excipients and their significant findings.     

Testosterone solid lipid microparticles for transdermal drug delivery. Formulation and physicochemical characterization

Purpose: The main objective of the study was to formulate and characterize testosterone (TS) solid lipid microparticles (SLM) to be applied as a transdermal delivery system.

Methods: Testosterone SLMs were formulated using an emulsion melt homogenization method. Various types and concentrations of fatty materials, namely glyceryl monostearate (GM), glyceryl distearate (GD), stearic acid (SA) and glyceryl behanate (GB) were used. The formulations contained 2.5 or 5?mg TS?g^?1. Morphology, particle size, entrapment efficiency (EE), rheological properties and thermal behaviour of the prepared SLM were examined. In vitro release characteristics of TS from various prepared SLM were also evaluated over 24?h using a vertical Franz diffusion cell. In addition, the effect of storage and freeze-drying on particle size and release pattern of TS from the selected formulation was evaluated.

Results: The results indicated that the type of lipid affected the morphology and particle size of SLM. A relatively high drug percentage entrapment efficiency ranging from 80.7–95.7% was obtained. Rheological studies showed plastic flow characteristics of the prepared formulations. DSC examination revealed that TS existed in amorphous form in the prepared SLM. Release studies revealed the following rank order of TS permeation through cellophane membrane after application of various formulations: 5% GM?<?5% GD?<?5% SA?<?5% GB?<?2.5% GM?<?2.5% SA?<?10% GD?<?10% GB. The drug permeation through excised abdomen rat skin after application of 10% GB–2.5?mg TS?g^?1 SLM was lower than that permeated through cellophane membrane. Moreover, SLM containing 10% GB–2.5?mg TS?g^?1 stored at 5°C showed good stability as indicated by the release study and particle size analysis. Trehalose showed high potential as a cryoprotectant during freeze drying of the selected SLM formulation.

Conclusions: The developed TS SLM delivery system seemed to be promising as a TS transdermal delivery system.     

塞来昔布固体脂质纳米粒的制备及其在大鼠体内的药动学

目的:制备塞来昔布固体脂质纳米粒,并考察大鼠灌胃给药后体内的药动学特征。方法:采用热熔乳化超声-低温固化法制备塞来昔布固体脂质纳米粒,并对制得的纳米粒进行表征。将12只Wistar大鼠随机分为为塞来昔布原料药组和塞来昔布固体脂质纳米粒组,灌胃给药剂量均为100 mg·kg^-1,采用高效液相色谱法测定大鼠血浆中塞来昔布的浓度,采用3P97程序计算塞来昔布药动学参数。结果:塞来昔布固体脂质纳米粒平均粒径为(183.6±44.5)nm,PdI为(0.217±0.052),Zeta电位为(-30.4±5.2)mV。塞来昔布原料药和塞来昔布固体脂质纳米粒在大鼠体内的AUC_(0-t)分别为(4.47±0.72)和(11.64±2.01)mg·L^-1·h;t_1/2分别为(13.45±1.89)和(10.12±1.24)h;t_max 分别为(2.33±0.21)和(1.31±0.14)h;C_max分别为(0.86±0.12)和(2.14±0.46 )mg·L^-1。结论:塞来昔布固体脂质纳米粒能够明显改善大鼠体内塞来昔布的药动学行为,与塞来昔布原料药相比具有明显的缓释效果,同时提高了药物的生物利用度。     

降香挥发油固体脂质纳米粒的制备工艺研究

目的研究降香挥发油固体脂质纳米粒制备中的主要影响因素。方法分别采用高压乳匀法和熔融 超声法制备了降香挥发油固体脂质纳米粒混悬液。以单因素考察和正交设计法研究制备工艺中影响降香挥发油固体脂质纳米粒质量的主要因素 ,筛选出较理想的处方和工艺。结果所得纳米粒为圆整的类球形实体粒子 ,表面光滑 ,平均粒径为 4 0 0nm和 34 5nm ,含药量为 72 11%和71 5 4 % ,包封率为 91 2 7%和 92 36 %。结论采用熔融 超声法制备降香挥发油固体脂质纳米粒实用性更强。