在T型微通道内制备固体脂质纳米粒(SLN)的实验研究

研究了一种用T型微通道制备固体脂质纳米粒(solid lipid nanoparticles,SLN)的新方法.以softisan100(C_(10)～C_(18)的混合脂)丙酮溶液作为脂相,以Poloxamer 188水溶液为水相,用注射泵分别将脂相和水相注入T型通道的主道和支道内,两相在交叉口接触后形成明显的相界面,并继续沿主道向前流动.脂相中丙酮通过相界面迅速向水相扩散,随着流体的向前运动,脂相中脂的浓度不断增大至过饱和而形成固体脂质纳米粒(SLN).实验考察了两相流速和微通道尺寸对SLN粒径大小和粒径分布的影响.结果表明:在实验条件下,制得的SLN粒径在110～350 nm之间,多分散性指数小于0.24;T型通道交叉口的流场分布受两相相对流速的影响,并直接影响成粒规律,在不出现两相返混条件下,保持水相流速不变,SLN粒径随脂相流速增大而增大;保持脂相流速不变,粒径随水相流速的增大略有增大;通道尺寸越小所制得粒径也越小.     

环孢素A固体脂质纳米粒制备工艺优化

为了制备单分散性优良、形态规整且具有较高包封率的环孢素A固体脂质纳米粒,采用溶剂扩散法制备环孢素A固体脂质纳米粒。在水相中加入海藻酸钠以改善纳米粒形态和单分散性,利用Ca2+与载药纳米粒胶体溶液中海藻酸钠发生配位反应形成海藻酸钙凝胶,在低离心转速下分离纳米粒并简便准确测定药物包封率。在单因素实验基础上,采用响应面设计优化载药纳米粒的制备工艺条件。结果表明,影响包封率显著因素为水含量和制备温度,在海藻酸钠用量0.1132 g、用水量52.77 mL、制备温度34.55℃优化条件下,纳米粒形态呈规整棒状,单分散性好,平均粒径为181.3 nm,平均包封率达82.45%。     

微通道内PCL-PEG-PCL载姜黄素纳米粒的制备及体外释药评价

目的:制备姜黄素载药纳米粒。方法:开环聚合法制备PCL-PEG-PCL三嵌段聚合物,微通道界面沉淀法制备姜黄素载药纳米粒,透射电镜观察纳米粒子形貌特征,动态光散射(DLS)测定粒径及其分布,HPLC测定纳米粒子的包封率和载药量,同时考察其体外释药性能。结论:姜黄素纳米粒平均粒径200 nm左右,粒径分布较窄,平均包封率(92.76±0.58)%,载药量(10.76±1.17)%,TEM观察纳米粒呈规则球形,10 d体外累积释药量76%。     

正交试验法优化白花丹醌固体脂质纳米粒的制备工艺

目的:制备白花丹醌固体脂质纳米粒,并采用正交试验法优化其处方工艺.方法:采用乳化-超声分散法制备白花丹醌固体脂质纳米粒,以包封率为评价指标,通过单因素试验,考察了乳化温度、超声功率、大豆卵磷脂和泊洛沙姆188的用量比例等因素对白花丹醌包封率的影响,并以正交试验优选最佳处方工艺.结果:通过单因素与正交试验优选的最佳处方工艺为脂质用量80 mg、乳化剂用量150 mg(比例为1︰5)、乳化温度60℃、超声功率300 W.按照最佳处方工艺制备3批白花丹醌固体脂质纳米粒,平均粒径为168.93 nm,平均包封率为59.74％.结论:最佳处方工艺制备的白花丹醌固体脂质纳米粒具有较好的包封率,工艺稳定可行.     

酮康唑固体脂质纳米粒体外评价

通过考察酮康唑固体脂质纳米粒体外透皮情况,由结果预测固体脂质纳米粒的发展前景.方法制备酮康唑固体脂质纳米粒,并测定2h、4h、6h、8h、12h、24 h时间点的药物累积透过皮肤与潴留于皮肤的量,通过数据分析评价药物在固体脂质纳米粒里的体外释放及透皮情况.结果药物在固体脂质纳米粒里的皮肤累积透过量低于含药1％的乳膏,但固体脂质纳米粒的皮肤潴留量明显高于含药1％的乳膏.结论固体脂质纳米粒可增加药物在皮肤的局部浓度从而增强药效,同时可减少药物透过真皮进入体循环从而减少副作用,具有良好的发展前景.     

表柔比星固体脂质纳米粒的制备及透黏膜行为

制备表柔比星固体脂质纳米粒(EPI-SLNs),并考察其体外释放、透黏膜行为.采用复乳法制备EPI-SLNs,并以包封率为评价指标优化其处方及工艺;采用平衡透析法研究EPI-SLNs的体外释药行为;立式扩散池法考察其透黏膜行为.结果表明,在m(表柔比星)=1 mg、m(单硬脂酸甘油酯)=5 mg、m(大豆磷脂)=3.5...     

布洛芬固体脂质微颗粒的制备及其晶体构型研究

An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.     

马钱子总碱脂质液晶纳米粒的制备及工艺优化

乙醇注入结合硫酸铵主动载药技术制备马钱子总碱脂质液晶纳米粒(LLCN).在筛选并确定脂质体制备方法的基础上,选择磷脂-胆固醇比、脂-药比、硫酸铵浓度、乙醇的体积为影响因素,以LLCN包封率为考察指标,单因素分析确定响应值,正交设计L9(34)优化处方参数,电镜检测LLCD的粒径、表面电荷,分析其稳定性.实验得出的最佳工...     

Preparation and Characterization of Catalase-Loaded Solid Lipid Nanoparticles Protecting Enzyme against Proteolysis

Catalase-loaded solid lipid nanoparticles (SLNs) were prepared by the double emulsion method (w/o/w) and solvent evaporation techniques, using acetone/methylene chloride (1:1) as an organic solvent, lecithin and triglyceride as oil phase and Poloxmer 188 as a surfactant. The optimized SLN was prepared by lecithin: triglyceride ratio (5%), 20-second + 30-second sonication, and 2% Poloxmer 188. The mean particle size of SLN was 296.0 ± 7.0 nm, polydispersity index range and zeta potential were 0.322-0.354 and -36.4 ± 0.6, respectively, and the encapsulation efficiency reached its maximum of 77.9 ± 1.56. Catalase distributed between the solid lipid and inner aqueous phase and gradually released from Poloxmer coated SLNs up to 20% within 20 h. Catalase-loaded SLN remained at 30% of H(2)O(2)-degrading activity after being incubated with Proteinase K for 24 h, while free catalase lost activity within 1 h.     

Surfactant Effect on the Physicochemical Characteristics of Solid Lipid Nanoparticles Based on Pillar[5]arenes

Novel monosubstituted pillar[5]arenes containing both amide and carboxyl functional groups were synthesized. Solid lipid nanoparticles based on the synthesized macrocycles were obtained. Formation of spherical particles with an average hydrodynamic diameter of 250 nm was shown for pillar[5]arenes containing N-(amidoalkyl)amide fragments regardless of their concentration. It was established that pillar[5]arene containing N-alkylamide fragments can form spherical particles with two different sizes (88 and 223 nm) depending on its concentration. Mixed solid lipid nanoparticles based on monosubstituted pillar[5]arenes and surfactant (dodecyltrimethylammonium chloride) were obtained for the first time. The surfactant made it possible to level the effect of the macrocycle concentration. It was found that various types of aggregates are formed depending on the macrocycle/surfactant ratio. Changing the macrocycle/surfactant ratio allows to control the charge of the particles surface. This controlled property will lead to the creation of molecular-scale porous materials that selectively interact with various types of substrates, including biopolymers.     

In Vitro Comparative Study of Solid Lipid and PLGA Nanoparticles Designed to Facilitate Nose-to-Brain Delivery of Insulin

The brain insulin metabolism alteration has been addressed as a pathophysiological factor underlying Alzheimer’s disease (AD). Insulin can be beneficial in AD, but its macro-polypeptide nature negatively influences the chances of reaching the brain. The intranasal (IN) administration of therapeutics in AD suggests improved brain-targeting. Solid lipid nanoparticles (SLNs) and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are promising carriers to deliver the IN-administered insulin to the brain due to the enhancement of the drug permeability, which can even be improved by chitosan-coating. In the present study, uncoated and chitosan-coated insulin-loaded SLNs and PLGA NPs were formulated and characterized. The obtained NPs showed desirable physicochemical properties supporting IN applicability. The in vitro investigations revealed increased mucoadhesion, nasal diffusion, and drug release rate of both insulin-loaded nanocarriers over native insulin with the superiority of chitosan-coated SLNs. Cell-line studies on human nasal epithelial and brain endothelial cells proved the safety IN applicability of nanoparticles. Insulin-loaded nanoparticles showed improved insulin permeability through the nasal mucosa, which was promoted by chitosan-coating. However, native insulin exceeded the blood-brain barrier (BBB) permeation compared with nanoparticulate formulations. Encapsulating insulin into chitosan-coated NPs can be beneficial for ensuring structural stability, enhancing nasal absorption, followed by sustained drug release.     

In Vivo Evaluation of Praziquantel-Loaded Solid Lipid Nanoparticles against S. mansoni Infection in Preclinical Murine Models

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs’ suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in S. mansoni-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.     

Solid Lipid Nanoparticle-Based Calix[n]arenes and Calix-Resorcinarenes as Building Blocks: Synthesis,Formulation and Characterization

Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. This paper presents an overview about the use of calix[n]arenes and calix-resorcinarenes in the formulation of SLNs. Because of their specific inclusion capability both in the intraparticle spaces and in the host cavities as well as their capacity for functionalization, these colloidal nanostructures represent excellent tools for the encapsulation of different active pharmaceutical ingredients (APIs) in the area of drug targeting, cosmetic additives, contrast agents, etc. Various synthetic routes to the supramolecular structures will be given. These various routes lead to the formulation of the corresponding SLNs. Characterization, properties, toxicological considerations as well as numerous corresponding experimental studies and analytical methods will be also exposed and discussed.     

Composites Based on Gellan Gum,Alginate and Nisin-Enriched Lipid Nanoparticles for the Treatment of Infected Wounds

Due to growing antimicrobial resistance to antibiotics, novel methods of treatment of infected wounds are being searched for. The aim of this research was to develop a composite wound dressing based on natural polysaccharides, i.e., gellan gum (GG) and a mixture of GG and alginate (GG/Alg), containing lipid nanoparticles loaded with antibacterial peptide—nisin (NSN). NSN-loaded stearic acid-based nanoparticles (NP_NSN) were spherical with an average particle size of around 300 nm and were cytocompatible with L929 fibroblasts for up to 500 µg/mL. GG and GG/Alg sponges containing either free NSN (GG + NSN and GG/Alg + NSN) or NP_NSN (GG + NP_NSN and GG/Alg + NP_NSN) were highly porous with a high swelling capacity (swelling ratio above 2000%). Encapsulation of NSN within lipid nanoparticles significantly slowed down NSN release from GG-based samples for up to 24 h (as compared to GG + NSN). The most effective antimicrobial activity against Gram-positive Streptococcus pyogenes was observed for GG + NP_NSN, while in GG/Alg it was decreased by interactions between NSN and Alg, leading to NSN retention within the hydrogel matrix. All materials, except GG/Alg + NP_NSN, were cytocompatible with L929 fibroblasts and did not cause an observable delay in wound healing. We believe that the developed materials are promising for wound healing application and the treatment of bacterial infections in wounds.     

非离子表面活性剂在纳米粒中的应用

综述了聚合物纳米粒和固体脂质纳米粒的有关研究进展,重点对非离子表面活性剂在聚合物纳米粒和固体脂质纳米粒制备方法、表面修饰中的应用进行了介绍,指出了非离子表面活性剂在纳米粒研究和应用中具有广阔的前景。