Preparation,characterization, and in vivo study of rhein solid lipid nanoparticles for oral delivery

In this study, rhein‐SLN s were successfully produced by hot homogenization followed by ultrasonication. Precirol ATO 5 in which rhein exhibited higher partition coefficient was selected for preparation of SLN s. In the dynamic light scattering, the rhein‐SLN s showed a smaller size with a mean value of 120.8 ± 7.9 nm and with zeta potential of ?16.9 ± 2.3 mV. SLN s exhibited a good stability during the period of 2 months. The SLN s indicated faster drug release with a burst release within 2 hr and followed by a sustained release with a biphasic drug‐release pattern. Comparing with the same concentration (free drug), the cellular cytotoxicity of rhein‐loaded SLN s increased significantly at the same incubation condition. In vivo, the AUC _0‐t of rhein in the form of SLN s was significantly increased and was 2.06‐fold that of suspensions group. The results showed an increased oral absorption and improved the oral bioavailability of rhein by the formulation of SLN s.     

Development and characterization of itraconazole-loaded solid lipid nanoparticles for ocular delivery

Abstract

The purpose of this study was to investigate the feasibility of entrapping water-insoluble drug itraconazole into solid lipid nanoparticles (SLNs) for topical ocular delivery. The drug-loaded SLNs were prepared from stearic acid and palmitic acid using different concentrations of polyvinyl alcohol employed as emulsifier. SLNs were prepared by the melt-emulsion sonication and low temperature-solidification method and characterized for particle size, zeta potential, drug loading and drug entrapment efficiency. The mean particle size of SLNs prepared with stearic acid ranged from 139 to 199?nm, while the SLNs prepared with palmitic acid had particle size in the range of 126–160?nm. The SLNs were spherical in shape. Stearic acid-SLNs showed higher entrapment of drug compared with palmitic acid-SLNs. Differential scanning calorimetry (DSC) and X-ray diffraction measurements showed decrease in crystallinity of drug in the SLN formulations. The modified Franz-diffusion cell and freshly excised goat corneas were used to test drug corneal permeability. Permeation of itraconazole from stearic acid-SLNs was higher than that obtained with palmitic acid-SLNs. The SLNs showed clear zone of inhibition against Aspergillus flavus indicating antimicrobial efficacy of formulations.     

Lung-targeting delivery of dexamethasone acetate loaded solid lipid nanoparticles

The objective of the present study was to develop a novel solid lipid nanoparticle (SLN) for the lung-targeting delivery of dexamethasone acetate (DXM) by intravenous administration. DXM loaded SLN colloidal suspensions were prepared by the high pressure homogenization method. The mean particle size, drug loading capacity and drug entrapment efficiency (EE%) of SLNs were investigated. In vitro drug release was also determined. The biodistribution and lung-targeting efficiency of DXM-SLNs and DXM-solutions (DXM-sol) in mice after intravenous administration were studied using reversed-phase high-performance liquid chromatography (HPLC). The results (expressed as mean +/- SD) showed that the DXM-SLNs had an average diameter of 552 +/- 6.5 nm with a drug loading capacity of 8.79 +/- 0.04% and an entrapment efficiency of 92.1 +/- 0.41%. The in vitro drug release profile showed that the initial burst release of DXM from DXM-SLNs was about 68% during the first 2 h, and then the remaining drug was released gradually over the following 48 hours. The biodistribution of DXM-SLNs in mice was significantly different from that of DXM-sol. The concentration of DXM in the lung reached a maximum level at 0.5 h post DXM-SLNs injection. A 17.8-fold larger area under the curve of DXM-SLNs was achieved compared to that of DXM-sol. These results indicate that SLN may be promising lung-targeting drug carrier for lipophilic drugs such as DXM.     

环孢素A纳米粒-凝胶制剂的制备及兔泪液药动学

目的制备环孢素A固体脂质纳米粒-原位凝胶复合制剂并考察其在家兔泪液中消除情况。方法采用乳化-超声法制备环孢素固体脂质纳米粒,用带正电的十八胺包衣以调节纳米粒表面的电性,用Cou lter LS 230测定纳米粒粒径,用电泳光散射法测定纳米粒的动电电位,将包衣纳米粒载于F127形成的原位凝胶中,考察制剂在家兔泪液中不同时间点药物浓度,以环孢素橄榄油滴眼液作对照,计算药物动力学参数。结果纳米粒粒径121 nm,动电电位+23 mv,纳米粒-凝胶制剂在家兔眼部经3 h的泪液代谢动力学参数AUC、MRT分别为蓖麻油制剂的3.4和4.0倍,包衣纳米粒的AUC和MRT也均比未包衣纳米粒有显著提高。结论环孢素A固体脂质纳米粒-原位凝胶制剂可显著提高环孢素在泪液中的浓度,延长作用时间,减少刺激性。     

Formulation of acyclovir-loaded solid lipid nanoparticles: 2. Brain targeting and pharmacokinetic study

Acyclovir (ACV) is widely used in the treatment of herpes encephalitis. The present study was conducted to prepare chitosan-tween 80 coated solid lipid nanoparticles (SLNs) as a delivery system for brain targeting of ACV in rabbits. The SLNs were prepared and coated in one step by microemulsion method using a coating solution containing chitosan (0.1% w/v) and tween 80 (2% w/v) for loading sustained release ACV. In vitro characterization was performed for coated ACV-SLNs. Concerning in vivo experiments; a single intravenous bolus dose of coated ACV-SLNs was given versus free ACV solution to rabbits (62?mg/kg). Plasma pharmacokinetic parameters were calculated from the ACV concentration-time profiles in plasma using the two compartmental analysis. The values of AUC_0?∞ and MRT of coated ACV-SLNs were higher than free drug by about twofold, 233.36?±?41.56?μg.h/mL and 1.81?±?0.36?h, respectively. The noncompartmental analysis was conducted to estimate the brain pharmacokinetic parameters. The AUC_0?∞ brain/AUC_0?∞ plasma ratio for coated ACV-SLNs and free ACV was 0.22 and 0.12, respectively. These results indicated the effectiveness of using coated ACV-SLNs for brain targeting.     

左旋多巴固体脂质纳米粒的制备及包封率测定

目的:用微乳法制备左旋多巴固体脂质纳米粒(LDP-SLN),并建立包封率的测定方法。方法:通过绘制三元相图,采用微乳法制备LDP-SLN,用TEM和激光粒度仪进行了颗粒形貌和粒径分布的研究,用葡聚糖凝胶层析法分离测定包封率。对其粒径、形态、包封率等理化性质进行研究,并考察其稳定性。结果:实验制得LDP-SLN为稳定的略泛蓝色乳光的纳米混悬液,在透射电镜下显示为较为均匀的球体,激光粒度测定平均粒径为108nm,多分散系数1.153;4℃放置2个月,粒径、包封率无显著变化。包封率测定的线性范围为2～100mg·mL-1,线性良好(r=0.9999),精密度符合要求,LDP-SLN上柱洗脱后分离度和回收率均符合要求。结论:该研究中制备了物理性质较为稳定的LDP-SLN,建立了合适的包封率测定方法,并考查初步稳定性较好。     

Preparation,characterization, and evaluation of gatifloxacin loaded solid lipid nanoparticles as colloidal ocular drug delivery system

This article describes the preparation and characterization of solid lipid nanoparticles (SLNs) prepared with stearic acid (SLN-A) and a mixture of stearic acid and Compritol (SLN-B) as lipid matrix and poloxamer-188 as surfactant, using sodium taurocholate and ethanol as co-surfactant mixture, with a view to applying the SLN in topical ocular drug delivery. The SLNs were prepared by o/w microemulsion technique and characterized by time-resolved particle size analysis, polydispersity index, zeta(ζ )-potential, differential scanning calorimetry (DSC), IR-spectroscopy, and wide-angle X-ray diffractometry (WAXD). The results obtained in these studies were compared with SLN prepared with stearic acid alone. IR, WAXD, and DSC studies revealed low-crystalline SLN and were having positive ζ -potentials after three-months of storage. Results indicated mixed lipid-matrix produced SLN with low-crystallinity and smaller particle sizes and higher drug entrapment compared with SLN prepared with stearic acid alone, therefore SLN-B would be suitable for the preparation of nanosuspension. Nanosuspensions were subjected to rheological and physicochemical evaluation, in vitro drug release and ex vivo corneal permeation studies and their effect were evaluated on corneal hydration-level. SLN composed of stearic acid and compritol would prove to be a good ocular drug delivery system considering the smaller particle size, particle size stability, and physiologically tolerable components.     

Preparation and characterization of nocodazole-loaded solid lipid nanoparticles

Abstract

Nocodazole (NCD) has more carcinogenic effect than similar drugs. Moreover, it has low drug release time and high particle size. Solid Lipid Nanoparticles (SLNs) have been evaluated for decrease in particle size and therefore increase in drug release time, for such drugs. In this study, NCD has been successfully incorporated into SLNs systems and remained stable for a period of 90 days. NCD structure related to the chemical nature of solid lipid is a key factor to decide whether anticarcinogenic agent will be incorporated in the long term and for a controlled optimization of active ingredient incorporation and loading, intensive characterization of the physical state of the lipid particles were highly essential. Thus, NMR, FT-IR, DSC (for thermal behavior) analyses were performed and the results did not indicate any problem on stability. Moreover, SLNs were decreased size of NCD in addition to increase in time of the drug release. After SLN preparation, particle size, polydispersity index, electrical conductivity and zeta potential were measured and drug release from NCD-loaded SLNs were performed. These values seem to be of the desired range.     

A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles

Iron (Fe) loaded solid lipid nanoparticles (SLN's) were formulated using stearic acid and iron absorption was evaluated in vitro using the cell line Caco-2 with intracellular ferritin formation as a marker of iron absorption. Iron loading was optimised at 1% Fe (w/w) lipid since an inverse relation was observed between initial iron concentration and SLN iron incorporation efficiency. Chitosan (Chi) was included to prepare chitosan coated SLN's. Particle size analysis revealed a sub-micron size range (300.3 ± 31.75 nm to 495.1 ± 80.42 nm), with chitosan containing particles having the largest dimensions. As expected, chitosan (0.1%, 0.2% and 0.4% w/v) conferred a net positive charge on the particle surface in a concentration dependent manner. For iron absorption experiments equal doses of Fe (20 μM) from selected formulations (SLN-FeA and SLN-Fe-ChiB) were added to Caco-2 cells and intracellular ferritin protein concentrations determined. Caco-2 iron absorption from SLN-FeA (583.98 ± 40.83 ng/mg cell protein) and chitosan containing SLN-Fe-ChiB (642.77 ± 29.37 ng/mg cell protein) were 13.42% and 24.9% greater than that from ferrous sulphate (FeSO4) reference (514.66 ± 20.43 ng/mg cell protein) (p ≤ 0.05). We demonstrate for the first time preparation, characterisation and superior iron absorption in vitro from SLN's, suggesting the potential of these formulations as a novel system for oral iron delivery.     

Preparation,characterization and in vitro activities evaluation of solid lipid nanoparticles based on PEG-40 stearate for antifungal drugs vaginal delivery

The present article reports the preparation, characterization and performance evaluation of solid lipid nanoparticles (SLNs) based on polyoxyethylene-40 stearate (PEG-40 stearate) for the administration of antifungal agents such as ketoconazole and clotrimazole. These nanoparticles could be useful in the treatment of vaginal infections sustained by Candida albicans. In particular, PEG-40 stearate was made to react with acryloyl chloride in order to introduce an easily polymerizable moiety for the creation of a second shell and to ensure a slow drug release. In addition, the differences on the release profiles between PEG-40 stearate-based nanoparticles, PEG-40 stearate acrylate based and polymerized ones, were analyzed under conditions, simulating the typical environment of Candida albicans infection. Then, the antifungal activity of nanoparticles was also evaluated in terms of minimal inhibitory concentration. Moreover, the nanoparticles were submitted to in vitro studies for evaluating the drug permeability at the site of action. Results indicated that the obtained particles are potentially useful for the treatment of vaginal infections sustained by Candida albicans.     

Development and characterization of 5-FU bearing ferritin appended solid lipid nanoparticles for tumour targeting

Ferritin coupled solid lipid nanoparticles were investigated for tumour targeting. Solid lipid nanoparticles were prepared using HSPC, cholesterol, DSPE and triolien. The SLNs without ferritin which has similar lipid composition were used for comparison. SLNs preparations were characterized for shape, size and percentage entrapment. The average size of SLNs was found to be in the range 110–152 nm and maximum drug entrapment was found to be 34.6–39.1%. In vitro drug release from the formulations is obeying fickian release kinetics. Cellular uptake and IC₅₀ values of the formulation were determined in vitro in MDA-MB-468 breast cancer cells. In vitro cell binding of Fr-SLN exhibits 7.7-folds higher binding to MDA-MB-468 breast cancer cells in comparison to plain SLNs. Ex-vivo cytotoxicity assay on targeted nanoparticles gave IC₅₀ of 1.28 µM and non-targeted nanoparticles gave IC₅₀ of 3.56 µM. In therapeutic experiments, 5-FU, SLNs and Fr-SLNs were administered at the dose of 10 mg 5-FU/kg body weight to MDA-MB-468 tumour bearing Balb/c mice. Administration of Fr-SLNs formulation results in effective reduction in tumour growth as compared with free 5-FU and plain SLNs. The result demonstrates that this delivery system possessed an enhanced anti-tumour activity. The results warrant further evaluation of this delivery system.     

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.     

布地奈德固体脂质纳米粒肺部给药系统的制备和评价(英文)

为改善布地奈德的溶解度和吸收,制备并评价了布地奈德固体脂质纳米粒(BUD-SLNs)。通过计算部分溶解度参数选择了单硬脂酸甘油酯作为脂材。经处方优化采用乳化-超声分散的方法制备的BUD-SLNs,包封率为(97.77±2.60)%;平均粒径是147.3nm,粒径分布均匀(PDI=0.228)。透射电镜下可见圆整颗粒。差热分析和X射线衍射实验的结果表明BUD以分子形式分散在SLNs中,体外释放结果表明BUD-SLNs符合双相动力学方程,属于均相骨架结构。研究结果为BUD-SLNs在肺部给药奠定了基础。     

齐墩果酸固体脂质纳米粒口服给药系统的制备与表征(英文)

采用改良的乳化-溶剂挥发法制备齐墩果酸-固体脂质纳米粒(OA-SLNs)并对其性质进行评价。其粒径,zeta电位,包封率和载药率分别为(104.5±11.7)nm,(-25.5±1.8)mV,(94.2±3.9)%,和(4.71±0.15)%。透射电子显微镜下,可见球形实心纳米粒。X-粉末衍射和差示扫描量热(DSC)图谱证实药物分子均匀分散在脂质骨架中。体外释放实验表明,OA-SLNs以每小时4.88%速率缓慢释放药物,符合零级释放动力学模型。OA-SLNs在人工胃液和肠液中具有良好的稳定性。本文研究为OA-SLNs口服给药系统的应用进一步研究提供了可能。     

Preparation and characterization of ibuprofen solid lipid nanoparticles with enhanced solubility

Solid lipid nanoparticles (SLNs) loaded with ibuprofen (IBU) were prepared by solvent-free high-pressure homogenization (HPH). The produced SLNs consisted of stearic acid, triluarin or tripalmitin as lipid matrixes and various stabilizers. The produced empty and IBU-loaded SLNs were characterized for particle size stability over 8 months. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were implemented to characterize the IBU state of freeze-dried SLNs. IBU was found to be in both amorphous and crystalline form within the lipid matrix. The lyophilized powders showed increased dissolution rates for IBU depending on the lipid nature. SLNs were incubated in Caco-2 cells for 24?h showing negligible cell cytotoxicity up to 15?mg/mL.     

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。