石蜡油w／o／w型多重乳液的制备及其对维生素C的包裹

以多重乳液相对体积为衡量标准,探讨了石蜡油、乳化剂、以及第一相质量分数对石蜡油w／o／w型多重乳液稳定性的影响。结果表明制备石蜡油w／o／w型多重乳液的较佳条件为：第一相中石蜡油和乳化剂Span80质量分数分别为40％和8％,第一相质量分数为65％,乳化剂Tween80质量分数为1％。采用透析-紫外分光光度法研究了该多重乳液对维生素c的包裹能力,结果表明：多重乳液可以有效包裹维生素C,包裹率达98．55％,且能缓慢释放被包裹的维生素C。     

Preparation of microcapsules of W/O/W emulsions containing a polysaccharide in the outer aqueous phase by spray‐drying

A water‐in‐oil‐in‐water (W/O/W) multiple emulsion containing a hydrophilic substance, 1,3,6,8‐pyrenetetrasulfonic acid tetrasodium salt (PTSA), and a wall material in its inner and outer aqueous phases, respectively, was prepared by a two‐step emulsification using a rotor/stator homogenizer, and was further homogenized with a high‐pressure homogenizer. Maltodextrin or gum arabic were used as wall materials, and olive oil was used as the oily phase. The high encapsulation efficiency for PTSA (>0.9) was realized. The emulsion was spray‐dried to produce microcapsules of W/O/W type. The efficiencies of the microcapsules prepared with maltodextrin and gum arabic were 0.82 and 0.67, respectively. Stability of the microcapsules was examined at 37 °C and 12%, 33% and 75% relative humidity. Microcapsules prepared with maltodextrin were more stable than those prepared with gum arabic.     

白油W/O/W型多重乳状液的稳定性研究

以多重乳状液相对体积为衡量标准,用显微镜直接观察,探讨了乳化剂的HLB值、质量分数、亲油亲水乳化剂体积比及油水的相比等对白油W/O/W型多重乳状液体系稳定性的影响。结果表明单一乳化剂体系中适宜的制备条件:乳液中乳化剂质量分数为12.2%,V(Span80)/V(Tween80)=7.5;适合多重乳液稳定的油水相比为:第一相体积比为2.5,第二相体积比为0.2。复合乳化剂体系中适宜的制备条件:第一相乳化剂的HLB值为6.5,V(复合乳化剂)/V(Tween80)=27.5,乳液中乳化剂质量分数为9.5%。     

Efficient Encapsulation of a Water-Soluble Molecule into Lipid Vesicles Using W/O/W Multiple Emulsions via Solvent Evaporation

We developed a novel method for preparing lipid vesicles with high entrapment efficiency and controlled size using water‐in‐oil‐in‐water (W/O/W) multiple emulsions as vesicle templates. Preparation consists of three steps. First, a water‐in‐oil (W/O) emulsion containing to‐be‐entrapped hydrophilic molecules in the water phase and vesicle‐forming lipids in the oil phase was formulated by sonication. Second, this W/O emulsion was introduced into a microchannel emulsification device to prepare a W/O/W multiple emulsion. In this step, sodium caseinate was used as the external emulsifier. Finally, organic solvent in the oil phase was removed by simple evaporation under ambient conditions to afford lipid vesicles. The diameter of the prepared vesicles reflected the water droplet size of the primary W/O emulsions, indicating that vesicle size could be controlled by the primary W/O emulsification process. Furthermore, high entrapment yields for hydrophilic molecules (exceeding 80 % for calcein) were obtained. The resulting vesicles had a multilamellar vesicular structure, as confirmed by transmission electron microscopy.     

脱氧氟尿苷脂质体的制备

目的建立脱氧氟尿苷(DFUR)脂质体的制备工艺。方法采用逆向蒸发法制备DFUR脂质体,并以包封率为参考指标,进行正交试验优化该脂质体的配方。以优化的配方制备脂质体,观察其微观形态,测定粒径、包封率及稳定性,并进行体外释药实验。结果制备DFUR脂质体的最佳配方为:卵磷脂/胆固醇(摩尔比)为2∶1,有机相/水相(体积比)为5∶1,DFUR浓度为2mg/ml,磷酸盐缓冲液pH值为7.0。以此配方制备,脂质体包封率可达52.15%。3批DFUR混悬液,粒径小于220nm的粒子比率均在70%以上,显微镜下观察可见,脂质体呈球形或椭圆形,粒径范围在0.15μm～1.00μm之间。4℃保存49d,脂质体的稳定性良好。其累积释放率远低于原料药浓度。结论已建立了DFUR脂质体的制备工艺,该工艺操作简便可靠,所需设备简单,稳定性较好,可用于包埋水溶性药物。     

快速膜乳化法制备载生长激素释放肽-6的PLGA微球

采用快速膜乳化法制备了聚(乳酸-羟基乙酸)(PLGA)微球,得到制备PLGA微球的优化条件为：过膜压力5 kPa,水相中PVA浓度19 g/L,油/水相体积比1:10,该条件下所制空白微球的平均粒径约为24 mm,粒径分布系数Span<0.7. 在此基础上制备载生长激素释放肽-6(GHRP-6)微球,油相乳化剂浓度2.5 g/L、外水相中NaCl浓度10 g/L条件下所制载GHRP-6微球包埋率最高可达85%,初乳制备方式对药物包埋率及体外释放行为均有较大影响,超声法制备的初乳所得微球内部结构紧密,药物包埋率较高(85%),但释药缓慢;而均质法制备的初乳所得微球内部结构疏松,药物包埋率较低(76.8%),但在体外释放更完全.     

Influence of Surfactant on the Characteristics of W1/O/W2-Microparticles

The water-in-oil-in water (W₁/O/W₂) double emulsion evaporation technique is widely used when the microencapsulation of soluble agents like naloxone HCl is intended. The present work shows the effect of HLB emulsifiers added to phase O on microsphere morphology, size, release, drug encapsulation efficiency. The addition of sorbitan ester to first emulsion (W₁/O) and the HLB of the surfactant have an important effect on the characteristics of poly-lactide-co-glycolide (PLGA) microparticles (MP). This MP with sorbitan esters added were smaller and released the hydrophilic drug, naloxone, with no-significant difference at pH 5 versus pH 7.5 (phosphate medium). This is an important fact when long-drug release is considered since it is known that PLGA degradation leads to media acidification. The HLB value had an important effect on drug loading. Sorbitan monooleate led to the highest naloxone loading. Because of its low HLB (4.3), it is most suitable for stabilizing the W₁/O emulsion, which is fundamental for the successful entrapment of a hydrophilic compound in MP prepared by double emulsion technique. Finally, drug solubility in the MP matrixes cannot be considered as a predictive parameter for drug encapsulation. Both surfactants increased the naloxone solubility in the polymer PLGA and only sorbitan monooleate increased the drug entrapment.     

The effect of process variables on the morphology and release characteristics of protein‐loaded PLGA particles

Poly(lactide‐co‐glycolide) (PLGA 75 : 25), IV 0.94 dL/g was chosen as the matrix of the microparticles. Bovine serum albumin (BSA) (Fraction V) as the model drug was incorporated in the microparticles by a W/O/W emulsification and solvent evaporation technique. The effect of the various preparation parameters on particle morphology, drug loading efficiency, and drug release profiles of the resultant microparticles were examined. Particle size varied from 5 to 60 μm. The final morphology of the microparticles varied dramatically with preparation variables such as equipment used to produce the primary emulsion (W1/O) and the water‐to‐oil ratio (W1/O) in the primary emulsion. In general, the viscosity of the primary emulsion had a significant effect on the porosity of particles produced. The release of BSA showed a strong relationship with the preparation parameters of microparticles, partly due to the morphological effects. For example, microparticles made from the vortex mixer that was used to disperse inner aqueous phase (W1) to oil phase (O) showed a lower burst effect than that made from the homogenizer because of its better surface morphology. W1/O ratio, speed of dispersing the primary emulsion into W2, PLGA concentration, and different matrix materials also affected the drug release profiles. In all the samples studied here, only diffusion‐controlled release was observed. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3053–3061, 2006     

Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.     

胰岛素W/O型微乳液的制备及体外释药性能

制备了包封胰岛素(INS)的Tween 80-Span 80/乙醇/丁酸乙酯/水体系的W/O型微乳液。以最大增溶水量为指标,选择了合适的微乳液组分包封INS。考察了温度、盐度和pH对微乳液区域的影响。电导率法区分了微乳液的O/W、W/O和B.C.区域。动态光散射测定了微乳液的粒径和多分散度。125I同位素示踪法测定了INS微乳液体外释放效果。结果表明,微乳体系在水/乙醇(质量比为1.8∶1)的质量分数小于41%时形成W/O型微乳液,温度、盐度升高和pH降低使微乳区稍有减小。微乳液粒径和多分散度分别为35~45 nm和0.29~0.37。pH的降低对微乳液粒径影响不大,而药物的加入使微乳液粒径略有减小。载药微乳液粒径在制备3 d后突降,以后的27 d内保持在37 nm左右。该载药微乳液在7.5 h后进入缓释阶段,40 h时INS的释放率为66.20%。     

5-FU-PLGA复乳微球的制备及体外释放

采用乳化溶剂挥发法制备W/O/W型5-FU-PLGA复乳微球,采用单因素设计考察了第一相体积比(内水相与油相)、第二相体积比(初乳与外水相)对复乳稳定性的影响,采用正交设计考察了搅拌温度、搅拌时间、辅料浓度和有机相中载体材料浓度对微球质量的影响,并对制备条件进行优化。最适宜制备条件为:第一相体积比为1:2,第二相体积比为1:1,搅拌温度为10 ℃、搅拌时间为6 h、辅料浓度为0.5%、有机相中载体材料浓度为15%。依据最适宜条件制备的微球圆整度良好、粒径范围窄,平均粒径5.20 μm,载药量为5.34%,包封率为77.22%。体外释放试验表明微球具有明显的缓释效果,释放行为符合Higuchi模型。     

Nanoencapsulation of Alpha-linolenic Acid with Modified Emulsion Diffusion Method

Nanocapsules of alpha-linolenic acid (α-LA) were prepared by a modified emulsion diffusion technique with encapsulation efficiency of 93%. Polylactic acid (PLA) was used as the encapsulating polymer with acetone and ethyl acetate as organic solvents, and Tween 20, gelatin and Pluronic-F68 in water as stabilizers. Two ratios of organic to aqueous phases were used with each solvent and stabilizer. Nanocapsule dispersions with a particle size less than 100 nm and a zeta potential as high as 33 mV were obtained as verified by scanning electron microscopy and the dynamic light scattering technique respectively. Both particle size and zeta potential were influenced by such preparation conditions as the type of stabilizer, type of organic solvent and the organic to aqueous phase ratio. Acetone was superior to ethyl acetate, and Tween 20 was superior to each of Pluronic-F68 and gelatin in obtaining smaller, less aggregated nanocapsules. An organic to aqueous phase ratio of 1:5 was shown to be more suitable for the formation of smaller nanocapsules, particularly when acetone was used as the organic solvent.     

快速膜乳化法制备胸腺法新长效缓释微球

采用快速膜乳化技术结合溶剂蒸发法制备以生物可降解聚乳酸-羟基乙酸(PLGA)为载体的胸腺法新载药微球,考察了PLGA分子量、油相中PLGA和乳化剂浓度、外水相pH值和内水相体积等对微球包埋率和粒径的影响. 结果表明,制备粒径均一的PLGA载药微球的优化条件为：PLGA分子量51 kDa,油相中PLGA和乳化剂浓度为100和10 g/L,内水相体积0.5 mL,外水相pH值为3.5. 该条件下所制载药微球粒径均一性好(Span<0.7),药物包埋率高达80%以上,突释率24 h内低于20%,线性持续稳定释药时间长达30 d.     

载阿奇霉素-鼠李糖脂胶束制备工艺优化及性能表征

采用薄膜水化法制备载阿奇霉素-鼠李糖脂(AZI-RHL)胶束，以包封率、载药量为评价指标，通过单因素试验和正交试验优化制备工艺，并考察其理化性质。制备载药胶束前先测定RHL水溶液的临界胶束浓度(CMC)。结果表明，RHL水溶液的CMC值约为0.25 mg/mL。优化后的最佳制备工艺条件为：RHL投料量100 mg，甲醇用量12 mL，搅拌时长20 min。在此条件下制备的AZI-RHL胶束呈球形，水动力学直径为136.3±68.5 nm，Zeta电位为-23.1±6.8 mV，包封率为80.34%±0.60%，载药量为19.42%±0.48%。红外光谱证明AZI包埋在胶束中。体外释放试验表明AZI-RHL胶束具有一定的缓释作用，其体外累计释放曲线符合Ritger-Peppas方程，释放药物以Fick扩散为主。综上所述，AZI-RHL胶束的制备工艺稳定可靠，胶束粒径小，且包封率、载药量高，是一种有潜力的新型制剂。     

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.     

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.     

快速膜乳化与热固化法制备粒径均一的pH敏感壳聚糖季铵盐凝胶微球

以具有升温自固化特性的壳聚糖季铵盐/甘油磷酸钠混合溶液为水相,利用快速膜乳化与热固化法制备了粒径均一、pH敏感的壳聚糖季铵盐凝胶微球,考察了跨膜压力、水油相组成、水油相体积比及微孔膜孔径等对微球粒径、结构和药物包埋率的影响. 结果表明,得到粒径698±57.33, 1145±71.48, 2021±53.63及3984±191.72 nm、粒径分布窄(多分散系数<0.1)、药物包埋率高达75.49%±2.62%的凝胶微球. 所制微球生物相容性好,有明显的pH敏感性,中性和碱性环境下结构稳定,药物缓释,pH=7.4时24 h内药物累计释放率为34.6%;酸性环境下微球崩解,药物快速释放,pH=5.5时1 h内药物累计释放率高达79.6%.     

Influence of the Oil Phase on the Microencapsulation by Complex Coacervation

The influence of oil type on the process yield, efficiency of encapsulation, particle size and morphological aspects of coacervated microparticles was investigated. Firstly, several factors affecting microencapsulation of oils by complex coacervation were simultaneously examined. The results indicated that the process yield is mainly dependent on the velocity of homogenization, temperature and polymer ratio. Using optimum conditions for producing microparticles [pH 4.0, 14,000 rpm, 50 °C, gelatin:gum arabic (GE:GA) 1:1 and 2.5 % w/v], different core materials were tested: a vegetable oil (almond oil), an oil with higher hydrophilic lipophilic balance (vetiver essential oil) and a highly hydrophobic oil (mineral oil). The oil phase exerted an influence on microparticle formation, disturbing the complexation of polymers and modifying the core distribution within the particles. Some of the polymers were complexed when mineral oil was used, and the highest efficiency of encapsulation (91.8 %) was obtained with vetiver oil, followed by the almond (70.6 %) and mineral (38.0 %) oils. Particles produced with vetiver oil were larger (43.5 μm) than those produced with mineral oil (35.0 μm) and almond oil (19.2 μm), and the increase in the size is due to the encapsulation of many small droplets of emulsion, characterizing these particles as multinucleate ones.     

芦丁脂质体的制备与药物包封率的测定

采用薄膜分散法,制备包封率高、粒径均匀、稳定性好的芦丁脂质体,并建立芦丁脂质体中芦丁含量和包封率的测定方法。以包封率为主要指标,通过正交设计优化芦丁脂质体的制备工艺,同时采用反相高效液相色谱法进行芦丁含量和包封率测定。结果表明,薄膜分散法制备的脂质体平均包封率为66.50%,外观均匀、稳定性良好。建立的反相高效液相色谱法能将芦丁与辅料分离良好,芦丁浓度在4～40μg/L范围内与峰面积呈现良好的线性关系（r=0.999 2,n=5）,平均回收率为99.0%,可用于测定芦丁脂质体的药物含量与包封率。     

水包油微乳法合成氧化铝纳米粒子

为了探索绿色、无污染的微乳法合成途径,采用水包油微乳法制备了氧化铝纳米粒子。Tween-80和醇作为表面活性剂和助表面活性剂,用超纯水来代替反相微乳液中大量的有机相,既经济又环保。研究了反应温度和反应物的浓度对反应产物的影响。实验结果表明:用水包油微乳液制备的氧化铝纳米粒子粒径小、分散性好。