Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC): Occlusive Effect and Penetration Enhancement Ability

Objective: This work compares the occlusive effect and the penetration enhancement ability of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), through in vitro skin. Methods: SLN and NLC were prepared by high shear homogenization and characterized by size, polydispersity index, zeta potential, morphology and physical stability. Occlusive effect was assessed by an in vitro test and by measuring TEWL using pig skin. Skin treated with the lipid carriers was visualized by SEM. A penetration test through skin, followed by tape stripping, was carried out using Nile red as a marker. Results: SLN (200 ± 6 nm) and NLC (192 ± 11 nm) were obtained. An occlusion factor of 36% - 39% was observed for both systems, while a reduction in TEWL of 34.3% ± 14.8% and 26.2% ± 6.5% was seen after treatment with SLN and NLC, respectively. SEM images showed a film formed by the lipid carriers, responsible for the occlusion observed. No differences were found between the occlusive effect produced by SLN and NLC in both tests. NLC allowed the penetration of a greater amount of Nile red than SLN: 4.7 ± 1.3 μg and 1.7 ± 0.4 μg, respectively. Conclusion: Both carriers form a film on the skin, providing an occlusive effect with no differences between these two systems. The penetration of a marker (Nile red) into the stratum corneum was quite higher for NLC than for SLN, suggesting an influence of the composition of these particles on their penetration enhancing ability.

Effect of types of solid lipids on the physicochemical properties and self-aggregation of amphotericin B loaded nanostructured lipid carriers(NLCs)

Amphotericin B (Am B), a polyene antibiotic, is one of the gold standards for the treatment of systemic fungal infections and leishmaniasis. Nowadays, only intravenous administration of Am B has been available;because Am B is poorly absorbed from the gastrointestinal (GI) tract due to its low aqueous solubility. Currently, 2 forms of Am B are available.

A hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier ocular drug delivery platform

The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier(NLC) drug delivery platform. An ophthalmic antiinflammatory drug, baicalin(BN) was chosen as the model drug. BN –NLC was prepared using melt-emulsification combined with ultra-sonication technique. Additionally, a dual pH-and thermo-sensitive hydrogel composed of carboxymethyl chitosan(CMCS) and poloxamer 407(F127) was fabricated by a cross-linking reaction with a nontoxic crosslinker genipin(GP). GP-CMCS/F127 hydrogel was characterized by FTIR, NMR, XRD and SEM. The swelling studies showed GP-CMCS/F127 hydrogel was both pH-and thermo-sensitive. The results of in vitro release suggested BN –NLC gel can prolong the release of baicalin comparing with BN eye drops and BN –NLC. Ex vivo cornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient(Papp) of BN –NLC gel was much higher(4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BN –NLC gel was confirmed that had no significant irritation to cornea. Ex vivo precorneal retention experiments were carried out by a flow-through approach. The results indicated that the NLC-based hydrogel can prolong precorneal residence time. In conclusion, the hybrid NLCbased hydrogel has a promising potential for application in ocular drug delivery.

Sustained-release genistein from nanostructured lipid carrier suppresses human lens epithelial cell growth

AIM： To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein（Gen-NLC） to inhibit human lens epithelial cells（HLECs） proliferation.·METHODS： Gen-NLC was made by melt emulsification method. The morphology, particle size（PS）, zeta potentials（ZP）, encapsulation efficiency（EE） and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier（NLC）, genistein（Gen） and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8（CCK-8） assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction（RT-q PCR） and immunofluorescence analyses.·RESULTS： The mean PS of Gen-NLC was 80.12±1.55 nm with a mean polydispersity index of 0.11±0.02. The mean ZP was-7.14 ±0.38 m V and the EE of Gen in the nanoparticles was 92.3% ±0.73%. Transmission electron microscopy showed that Gen-NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72 h. The CCK-8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The m RNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group.·CONCLUSION： Sustained drug release by Gen-NLCs may impede HLEC growth.

Optimization of indomethacin loaded nanostructured lipid carriers

Topical administration is the most common and acceptable use for the treatment of ocular disease.However,the major problem of ocular drug delivery is the rapid drug elimination from the pre-ocular area leading to poor ocular bioavailability[1].Nanostructure lipid carriers(NLC)possess a significant enhancement in ocular bioavailability by increasing the permeability and mucoadhesive property[2].In this study,indomethacin(IND),non-steroidal anti-inflammatory,was used as a model drug[3].

Development of a topical ointment of betamethasone dipropionate loaded nanostructured lipid carrier

The purpose of this study was to design an innovative topical ointment containing betamethasone dipropionate loaded nanostructured lipid carrier (BD-NLC) for the treatment of atopic dermatitis (AD). BD-loaded NLC was produced with precirol ATO 5 and oleic oil (OA) by melt emulsification method. Effects of surfactant concentration, amount of solid lipid and liquid lipid on skin retention and skin penetration were investigated by in vitro percutaneous permeation experiment. The optimized BD-NLC showed a homogeneous particle size of 169.1 nm (with PI = 0.195), negatively charged surface (-23.4 mV) and high encapsulation efficiency (85%). Particle morphology assessed by TEM revealed a spherical shape. In vitro skin permeation study was carried out to investigate the percutaneous behaviors of W/O ointment with BD-NLC and Carbopol emulgel ointment with BD-NLC. W/O ointment with BDNLC showed high skin retention (35.43 μg/g) and low penetration (0.87 μg/ml). In vitro drug release studies were carried out to demonstrate the drug releasing properties of the two ointments. W/O ointment with BD-NLC showed an advantage for skin retention as it was better for drug release. The tissue distribution test suggested that BD distribution was skin > muscle > blood. Self-made topical ointment in mice showed no skin irritation. The animal experiments indicated that BD-loaded NLC ointment was effective and safe for topical use.

Spray drying of fenofibrate loaded nanostructured lipid carriers

The conversion of aqueous dispersion of nanostructured lipid carriers(NLCs) into dry powder by spray drying could be a useful approach to render NLCs with better physical chemical stability than the aqueous dispersion. In this study, aqueous NLC dispersion containing fenofibrate was converted into dry, easily reconstitutable powder using spray drying. A central composite face centered design(CCFD) was used to investigate the influence of the ratio of lipid to protectant(mannitol and trehalose) and crystallinity of spray-dried powder on the particle size, yield and residual moisture content of the dried powder. A linear relationship(R2= 0.9915) was established between the crystalline content of the spray-dried powders against the ratio of mannitol to trehalose from 3:7 to 10:0(w/w). Spray drying of NLC aqueous dispersion using a mannitol and trehalose mixture resulted in an increase in particle size of the NLCs after reconstitution in water as compared to that in the initial aqueous dispersion. The decrease in crystallinity of the dry powder by reducing the ratio of mannitol to trehalose could improve the reconstitution of the NLCs in water. However the yield and residual moisture content of dry powder decreased with an increase in the ratio of mannitol to trehalose. Lipid nanoparticles were able to retain the drug incorporation and the prolonged drug release profile after spray drying. The experimental model was robust, and suggested that spray drying is a viable technique for the conversion of NLCs into dry powder.

Capillary electrophoresis to determine entrapment efficiency of a nanostructured lipid carrier loaded with piroxicam

A simple and fast capillary electrophoresis method has been developed to determine the amount of piroxicam loaded in a drug delivery system based on nanostructured lipid carriers（NLCs）.The entrapment efficiency of the nanostructured lipid carrier was estimated by measuring the concentration of drug not entrapped in a suspension of NLC.The influence of different parameters on migration times,peak symmetry,efficiency and resolution was studied;these parameters included the pH of the electrophoretic buffer solution and the applied voltage.The piroxicam peak was obtained with a satisfactory resolution.The separation was carried out using a running buffer composed of 50 mM ammonium acetate and 13.75 mM ammonia at pH 9.The optimal voltage was 20 kV and the cartridge temperature was 20 ℃.The corresponding calibration curve was linear over the range of 2.7-5.4 μg/mL of NLC suspension.The reproducibility of migration time and peak area were investigated,and the obtained RSD%values（n = 5） were 0.99 and 2.13.respectively.

Preparation and Characterization of Nanostructured Lipid Carrier Loaded with UVA/UVB Filters

A new photoprotective system based on encapsulating UVA (butyl methoxydibenzoylmethane, BMBM) and UVB (octyl methoxycinnamate, OMC) filters into nanostructured lipid carriers (NLC) has been prepared to develop cosmetic formulations with effective UV protection. BMBM/OMC-loaded NLC was prepared by ultrasonication-homogenisation, and analysed by particle size, zeta potential (ZP), encapsulation efficiency (EE), scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Moreover, the UV protection property and photostability were investigated and compared with BMBM/OMC-conventional emulsions. The particle size and ZP of BMBM/OMC-loaded NLC were 310.24 nm and -33.6 mV, EE of BMBM and OMC were 85.46% and 99.32%. SEM, FTIR and DSC analysis confirmed BMBM and OMC entrapped in the lipid matrix core and the structure was stable during storage. Compared with conventional emulsion, BMBM/OMC-loaded NLC displayed perfect photo protection property in whole UV range. The photostability studies showed that the NLC can improve the photostability of sunscreens.

Preparation and characterization of a nanostructured lipid carrier for phenylethyl resorcinol

Phenylethyl resorcinol(PR)demonstrates inhibitory effects on multiple targets in the melanin synthesis pathway,resulting in a strong whitening effect.However,challenges such as limited solubility in water and susceptibility to oxidation and discoloration restrict its practical application in the cosmetics industry.In order to enhance stability and performance characteristics,a whitening nanostructured lipid carrier(NLC)was synthesized through high-pressure homogenization.This method entailed the incorporation of solid lipids,a liquid lipid,and a compound emulsifier,with deionized water fulfilling the roles of solid phase,liquid phase,and water phase,respectively.The NLC's particle size,Zeta potential,stability,encapsulation efficiency,and other parameters were assessed using techniques such as particle sizer,stability analyzer,and HPLC.The results showed that the NLC for phenylethyl resorcinol prepared by using the optimal formula(7.50%solid lipids,3.00%ethylhexyl palmitate,and 2.00%Tween 80 and soybean lecithin)has an encapsulation efficiency of 87.11%,a particle size of 157.2±0.70 nm,a kinetic instability of less than 1.2,and a greatly improved stability,thereby successfully solving the problems of unstable storage and poor solubility of phenylethyl resorcinol.

基于Cur-NLCs的多重响应性微球的构建与评价

纳米结构脂质载体(nanostructured lipid carriers,NLCs)是提高姜黄素(curcumin,Cur)口服生物利用度的有效手段,常规条件制备的Cur-NLCs分散液稳定性及其应用领域有待研究和开发。作者采用电喷法复合Cur-NLCs和磁性明胶,构建具有多重响应性的微球,研究含有不同质量分数磁性明胶的微球粒径、外观形态、微观形态、储存稳定性、多重响应性和释放特性。结果表明:所制备的微球表面粗糙,呈椭球形,且随着磁性明胶质量分数的增加,粒径从(231.67±2.82)μm降低到(175.22±1.96)μm,呈减小趋势。微球在储存过程中稳定性良好,4℃下储存28 d,Cur保留率在80%以上。多重响应性研究显示,微球对磁性、温度、酸性和NaCl敏感。体外释放实验证明,微球具有S形Cur释放曲线,释放介质的pH和NaCl影响Cur的释放。研究表明,构建的微球是具有多重响应性且稳定性良好的智能递送体系,对拓展Cur-NLCs在食品工业中的应用以及智能递送系统的开发具有参考价值。

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。

基于耗散粒子动力学模拟辅助的纳米结构脂质载体优化制备

基于分子模拟能够探究纳米结构脂质载体(nanostructure lipid carriers,NLC)各物质间的结合能、溶解度参数等,预测混合物的相容性,从而用于指导实验前原料种类以及用量选择。该文以姜黄素(curcumin,Cur)为模型营养物,以固体脂质(单硬脂酸甘油酯)和液体脂质(中链甘油三酯、葵花籽油、甜橙油)及表面活性剂(泊洛沙姆188、卵磷脂、吐温-80)作为筛选对象,采用耗散粒子动力学(dissipative particle dynamics,DPD)方法进行模拟筛选,再通过正交试验制备NLC以对模拟结果进行验证,最后对NLC的粒径和微观形态等进行表征。模拟与实验结果均表明,单硬脂酸甘油酯-中链甘油三酯(medium chain triglycerides,MCT)-卵磷脂能形成较好的载体体系,固液脂质比为1∶3(质量比),卵磷脂含量为5%(质量分数),姜黄素含量占总脂质的3%(质量分数)时形成的球壳结构最好。优化后制备的姜黄素NLC平均粒径为(233.8±2.4)nm,电位为(-38.2±0.6)mV,包封率为85.06%,微观形态均匀分散、没有明显聚集现象。

紫草素纳米结构脂质载体的制备与评价

目的 制备并优化紫草素纳米结构脂质载体(NLC),并对其进行表征、创面刺激性测试及抗炎活性评价。方法 通过饱和溶解度测定、脂质相容性和乳化能力筛选了紫草素NLC的处方。以粒径和多分散系数(PDI)为指标,考察紫草素NLC的制备方法,并采用该方法制备紫草素NLC,单因素法考察固液脂质比、总脂质用量、乳化剂用量和投药量的范围。通过正交试验考察固液脂质比、总脂质用量、投药量对PDI和载药量的影响,得到最优处方,并对其进行验证及表征。通过在大鼠背部表皮造成破损后连续给药,测试紫草素NLC的创面刺激性。采用脂多糖诱导RAW264.7细胞炎症模型,以NO释放率为指标评价紫草素NLC的体外抗炎活性。结果 采用Transcutol P为液体脂质,固体脂质为双硬脂酸甘油酯,乳化剂为BRIJ?O20,采用薄膜水化法制备NLC,最优处方:乳化剂用量为6%,固液脂质比为4∶6,总脂质用量为6%,投药量为20 mg。大鼠背部破损皮肤均未见红斑或水肿,皮肤组织结构均基本正常,同时等剂量下的紫草素NLC抑制RAW264.7释放NO的能力存在比紫草素更强的趋势。结论 制得的紫草素NLC载药量高,粒径均一。紫草素被制成NLC后,对创面无刺激性,细胞毒性有所下降,同时具有较好的抗炎活性。

白藜芦醇纳米结构脂质载体的制备与体外释放研究

目的 制备白藜芦醇纳米结构脂质载体(Res-NLCs),并对其进行理化性质和体外释放特性的考察。方法 采用乳化蒸发-高压均质法制备Res-NLCs,通过正交试验得出最优处方,并对最优处方制得的Res-NLCs进行理化性质考察;通过HPLC建立白藜芦醇体外释放方法学,采用动态透析法对Res-NLCs的体外释药特性进行考察。结果 Res-NLCs的最优处方为:双硬脂酸甘油酯用量为0.0356 g,大豆磷脂用量为0.3918 g,Tween-80的质量浓度为4.25%,辛酸癸酸聚乙二醇甘油酯用量为0.0475 g。经透射电镜观察Res-NLCs呈规则圆球状,分散均匀。测得Res-NLCs的平均粒径为(81.87±0.14)nm,多分散系数为(0.099±0.02),Zeta电位为(-8.09±0.75)m V,包封率为(98.43±0.07)%,载药量为(11.04±0.14)%。体外释放结果显示,白藜芦醇溶液在8 h释放97.31%,而Res-NLCs则缓慢持续释放,并在48 h后达到释放平台,累计释放的白藜芦醇为80.69%。结论 通过乳化蒸发-高压均质法制备的Res-NLCs粒径小,分散均匀,具有较高的包封率及载药量,并可显著延长白藜芦醇释放的时间,具有良好的缓释效果。

羟基频哪酮视黄酸酯纳米结构脂质载体的体外透皮效果

采用微乳法制备羟基频哪酮视黄酸酯(hydroxypinacol retinoate,HPR)纳米结构脂质载体(nanostructured lipid carrier,NLC),简称HPR-NLC。利用离体猪皮和Franz扩散池渗透装置对该脂质载体进行体外透皮试验,并与HPR非包裹体做透皮效果比较。在不同时间收集接收液样本,用液相色谱法测定接收液中HPR的质量浓度,计算其累积透过量,通过累计透过量-时间曲线评估2种不同工艺HPR样品的透皮吸收效果,同时检测猪皮中HPR的滞留量。结果表明,NLC更有助于HPR的透皮渗透,24 h时NLC中HPR的累积透过量为26.48μg/cm2,是非包裹体的9倍;猪皮中HPR的平均滞留量为4.32μg/cm2,是非包裹体的6.5倍。

槲皮素纳米结构脂质载体的处方与制备工艺优化

目的:对槲皮素纳米结构脂质载体(Q-NLC)的处方与制备工艺进行优化和评价。方法:以粒径大小、多分散指数和Zeta电位等作为质量评价指标,采用单因素试验优化槲皮素纳米结构脂质载体的制备工艺;采用透射电子显微镜观察槲皮素固体脂质纳米粒的微观形态;采用紫外分光光度法测定槲皮素的药物包封率。结果:所制备的Q-NLC为白色乳光的透明乳液,在透射电镜下呈圆形或圆球形状。最优的制备条件为采用溶剂乳化超声法,药物用量为5.0 mg的槲皮素粉末,0.975 g单硬脂酸甘油酯、0.150 g聚乙二醇单硬脂酸酯、0.300 g辛酸癸酸聚乙二醇甘油酯,泊洛沙姆188质量分数为1.0%,纳米结构脂质载体质量浓度为1 mg/mL,制备条件为在400 r/min以及70℃水浴条件下磁力搅拌时间15 min,超声搅拌时间为5 min。槲皮素在0.056~3.12μg/mL范围内线性关系良好,经测定槲皮素固体脂质纳米粒中药物含量为3.12μg/mL,包封率为39.42%±1.12%。结论:经优化制备的Q-NLC分散性好,包封率高,具有良好的稳定性,有望为槲皮素纳米药物的开发和应用提供实验基础。

Preparation of the nanostructured lipid carriers of artemisinin and its pharmacokinetic evaluation

Artemisinin（ART） is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipid carriers（NLCs） were proposed as carrier of ART to improve pharmacokinetic properties of the drug. ART-NLC was prepared by high-pressure homogenization based on orthogonal design. The particle size, zeta potential, encapsulation efficiency（EE） and percentage of drug loading（DL） of ART-NLC were（53.06±2.11） nm,（–28.7±3.59） m V, 73.9%±0.5% and 11.23%±0.37%, respectively. ART-NLC showed the sustained release characteristics and scarcely the hemolysis effect on human red blood cells. The pharmacokinetics of ART-NLC for rats after tail intravenous injection（i.v） or intraperitoneal injection（i.p） were investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. And ART solution was designed as control preparation. For rats of i.v groups, the AUC0–∞（（707.45±145.65） ng·h/m L） of ART-NLC were significantly bigger than that of ART（（368.98±139.58） ng·h/m L）. The MRT（（3.38±0.46） h） of ART-NLC was longer than that of ART（（1.39±0.61） h）. And similar results were observed for rats of i.p groups. The AUC0–∞（（1233.06±235.57） ng·h/m L） and MRT（（4.97±0.69） h） of ART-NLC were both bigger than those of ART, which were（871.17±234.03） ng·h/m L） and（1.75±0.31） h）, respectively. Compared with ART, ART-NLC showed a significant increase in AUC0–∞（P〈0.05） and MRT（P〈0.001） for both i.p and tail i.v administrations.

Folate and cell penetrating peptide modification effects on penetration behavior of nanostructured lipid carriers using multicellular tumor spheroids

Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.

冰片修饰的丹参酮ⅡA口服脑靶向pNLC的制备及质量评价

目的制备冰片修饰的丹参酮IIA PEG化纳米脂质载体(Bo-TA-pNLC)口服脑靶向给药系统,并对其进行质量评价。方法以Precirol ATO 5(主要成分甘油棕榈酸硬脂酸酯)及中链甘油三酯为固/液脂质材料,聚乙二醇硬脂酸酯15(Solutol HS15)为乳化剂,采用乳化蒸发-低温固化法制备Bo-TApNLC,通过正交试验优化处方,并对最优处方所制备的纳米脂质载体的形态、粒径、Zeta电位、包封率及体外释药行为进行考察。结果最优处方中固/液脂质比为7:1,Bo-TA-pNLC呈较规则的球形,平均粒径为102.49 nm,Zeta电位为-21.11 mV,平均包封率为84.12%,丹参酮IIA体外96 h内累积释放率为48.13%。结论采用乳化蒸发-低温固化法制备的Bo-TA-pNLC粒径分布均匀、包封率较高,且具有明显的体外缓释特征。