Optimization of the emulsification and solvent displacement method for the preparation of solid lipid nanoparticles

Objective: The essential aim of this article is to prepare solid lipid nanoparticles (SLNs) by emulsification and solvent displacement method and to determine the best process conditions to obtain submicron particles. Methods: The emulsification and solvent displacement method is a modification of the well-known emulsification–diffusion method, but without dilution of the system. The extraction of the partially water-miscible solvent from the emulsion globules is carried out under reduced pressure, which causes the diffusion of the solvent toward the external phase, with subsequent lipid aggregation in particles whose size will depend on the process conditions. The critical variables affecting the process, such as stirring rate, the proportion of phases in the emulsion, and the amount of stabilizer and lipid, were evaluated and optimized. Results: By this method, it was possible to obtain a high yield of solids in the dispersion for the lipids evaluated (Compritol^® ATO 888, Geleol^®, Gelucire^® 44/14, and stearic acid). SLNs of up to ～20 mg/mL were obtained for all lipids evaluated. A marked reduction in size, between 500 and 2500 rpm, was seen, and a transition from micro- to nanometric size was observed. The smaller particle sizes obtained were 113 nm for Compritol^® ATO 888, 70 nm for Gelucire^® 44/14, 210 nm for Geleol^®, and 527 nm for stearic acid, using a rotor–stator homogenizer (Ultra-Turrax^®) at 16,000 rpm. The best phase ratio (organic/aqueous) was 1 : 2. Conclusions: The process proposed in this study is a new alternative to prepare SLNs with technological potential.     

Paclitaxel-loaded lipid nanoparticles prepared by solvent injection or ultrasound emulsification

Lipid nanoparticles were fabricated as an injectable carrier system for paclitaxel. The components for the lipid matrix were based on phospholipids, and sucrose fatty acid ester was used as an emulsifier. Formulation prepared with solvent injection has a slightly larger particle size (187.6 nm) than the formulation (147.7 nm) prepared with ultrasound emulsification. Differential scanning calorimetry results indicated that paclitaxel entrapped in the lipid nanoparticles existed in an amorphous state in the lipid matrix. In vitro drug release was rather slow; only 12.5-16.5% of the drug released from the formulations within 14 days. Lipid nanoparticles demonstrated their potential as a promising pharmaceutical formulation of paclitaxel.     

A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity

To improve the anti-tumor activity of hydrophobic drug curcumin, we prepared curcumin-loaded PLGA nanoparticles （PLGA-Cur NPs） through a modified spontaneous emulsification solvent diffusion （modified-SESD） method. The influence of main preparation parameters was investigated, such as the volume ratio of binary organic solvents and the concentration of surfactant. Results indicated that the synthesized regular spherical PLGA NPs with the average diameter of 189.7 nm exhibited relatively higher yield （58.9%）, drug loading （11.0% （w/w）） and encapsulation efficiency （33.5%）, and also a controllable drug release profile. In order to evaluate the in vitro cytotoxicity of the prepared NPs, MTT assay was conducted, and results showed that the NPs could effectively inhibit HL60 and HepG2 cells with lower IC50 values compared with free curcumin. Furthermore, confocal microscopy together with flow cytometry analysis proved the enhanced apoptosis-inducing ability of PLGA-Cur NPs. Polymeric NP formulations are potential to be used for hydrophobic drug delivery systems in cancer therapy.     

Preparation of PLGA nanoparticles using TPGS in the spontaneous emulsification solvent diffusion method

D-alpha-tocopheryl poly (ethylene glycol) 1000 succinate (TPGS) is a widely used form of vitamin E that has been used as a solubilizer, an emulsifier and as a vehicle for drug delivery formulations. In this study, poly lactide-co-glycolide (PLGA) nanoparticles were prepared by spontaneous emulsification solvent diffusion (SESD) method. TPGS as an emulsifier and further as a matrix material blended with PLGA was used to enhance the encapsulation efficiency and improve the drug release profile of nanoparticles. Rifampicin and estradiol valerate were used as model drugs with different water solubility. The effect of formulation parameters such as drug/polymer ratio, oil phase combination, volume and surfactant content was evaluated. The surface morphology and size of the nanoparticles were studied by scanning electron microscopy (SEM) and laser light scattering. Drug encapsulation efficiency and in vitro drug release profiles of nanoparticles were determined using high performance liquid chromatography (HPLC). The nanoparticles prepared in this study were spherical with size range of 150–250?nm. It was shown that TPGS was a good emulsifier for producing nanoparticles of hydrophobic drugs and improving the encapsulation efficiency and drug loading and drug release profile of nanoparticles. However, the drug loading efficiency of rifampicin, a slightly water-soluble molecule, was significantly lower than that of estradiol valerate, a water insoluble molecule.     

Bortezomib-loaded solid lipid nanoparticles: preparation,characterization, and intestinal permeability investigation

Bortezomib (BTZ), a proteasome inhibitor, is clinically used for the treatment of multiple myeloma and mantle cell lymphoma via intravenous or subcutaneous administration. Since BTZ has limited intestinal permeability, in this study, solid lipid nanoparticles (SLNs) were selected as lipid carrier to improve the intestinal permeability of BTZ. The nanoparticles were prepared by hot oil-in-water emulsification method and characterized for physicochemical properties. Moreover, in situ single-pass intestinal perfusion technique was used for intestinal permeability studies. Mean particle size of the BTZ-loaded solid lipid nanoparticles (BTZ-SLNs) was 94.6?±?0.66?nm with a negative surface charge of –18?±?11?mV. The entrapment efficiency of the BTZ-SLNs was 68.3?±?3.7% with a drug loading value of 0.8?±?0.05%. Cumulative drug release (%) over 48?h, indicated a slow release pattern for nanoparticles. Moreover, the SEM image showed a spherical shape and uniform size distribution for nanoparticles. Also, FTIR analysis indicated that BTZ was successfully loaded in the SLNs. The results of the intestinal perfusion studies revealed an improved effective permeability for BTZ-SLNs with a P_eff value of about threefold higher than plain BTZ solution.     

Functionalized solid lipid nanoparticles for transendothelial delivery

The objectives of this study were to synthesize and characterize functionalized solid lipid nanoparticles (fSLN) to investigate their interaction with endothelial cell monolayers and to evaluate their transendothelial transport capabilities. fSLN bearing tetramethylrhodamine-isothiocyanate-labeled bovine serum albumin (TRITC-BSA) and Coumarin 6 were prepared using a single-step phase-inversion process that afforded concurrent surface modification with a variety of macromolecules such as polystyrene sulfonate (PSS), poly-L-lysine (PLL), heparin (Hep), polyacrylic acid (PAA), polyvinyl alcohol, and polyethylene glycol (PEG). TRITC-BSA/Coumarin 6 encapsulated in fSLN with composite surface functionality (PSS-PLL and PSS-PLL-Hep) were also investigated. Size and surface charge of fSLN were analyzed using dynamic light scattering and transmission electron microscopy. Transport across bovine aortic endothelial cell (BAEC) monolayers was assessed spectrophotometrically using a transwell assay, and fSLN localization at the level of the cell and permeable support was analyzed using fluorescence microscopy. fSLN with tunable size and surface functionality were successfully produced, and had significant effects on cell localization and transport. Specifically, fSLN with PSS-PLL-Hep composite surface functionalization was capable of translocating 53.2 +/- 8.7 mug of TRITC-BSA within 4 h, with fSLN-PEG, fSLN-PAA, and fSLN-PSS exhibiting near-complete apical, paracellular, and cytosolic localization, respectively. Coumarin 6 was released by fSLN as indicated by dye labeling of BAEC membranes. We have developed a rapid process for the production of fSLN bearing low- and high-molecular-weight payloads of varying physicochemical properties. These findings have impications for drug delivery and bioimaging applications, since due to tunable surface chemistry, fSLN internalization and/or translocation across intact endothelial cell monolayers is possible.     

Mannosylated solid lipid nanoparticles for lung-targeted delivery of Paclitaxel

Objective: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using mannose as a lectin receptor ligand conjugate for lung cancer targeting and to increase the anticancer activity of PTX against A549 lung’s epithelial cancer cells.

Materials and methods: The PTX-SLNs were prepared by solvent injection method and mannose was conjugated to the free amine group of stearylamine. The M-SLNs obtained were characterized for their particle size, polydispersity index, zeta potential and morphology by transmission electron microscope.

Results: The M-SLNs were spherical in shape with 254?±?2.3?nm average size, positive zeta potential (3.27?mV), 79.4?±?1.6 drug entrapment efficiency and showed the lower extent of drug release 40% over 48?h in vitro. Cytotoxicity study on A549 cell lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher concentration of PTX as compared to PTX-SLNs in an alveolar cell site.

Discussion and conclusion: These results suggested that mannosylated M-SLNs are safe and potential vector for lung cancer targeting.     

Preparation and characterization of camptothecin solid lipid nanoparticles

Camptothecin (CA), an antitumor drug, was incorporated into solid lipid nanoparticles (SLNs) prepared by high-pressure homogenization. A Taguchi orthogonal experimental design was used to study the influence of four different variables, with each variable having three value levels on nanoparticle size. Analysis of variance (ANOVA) has been used to evaluate the preparation of CA-SLNs and perform product optimization. The optimized CA-SLNs suspension was lyophilized using mannitol and glucose as cryoprotectants. The physicochemical characteristics of CA-SLNs were evaluated using transmission electron microscopy (TEM), electrophoresis, and differential scanning calorimetry (DSC). The release of camptothecin from CA-SLNs in various media was evaluated using a high-performance liquid chromatography (HPLC) method. The results showed that the concentration of emulsifier and the homogenization pressure had a significant influence on the particle size. The optimized CA-SLNs had an average diameter of about 200 nm, exhibited monodispersity with Dw/Dn of 1.06, and carried a negative charge. The optimal cryoprotectants consisted of 10% mannitol and 5% glucose in nanoparticle suspension. Lyophilized product was reconstituted in distilled water within 0.5 min without change of nanoparticle size. Camptothecin might exist in an amorphous state in SLNs. In vitro results showed that drug release was achieved for up to one week, and the released camptothecin quickly changed to open carboxylate form in the biological pH phosphate buffer. The results indicate that SLNs might be good potential sustained-release delivery vehicles for camptothecin or other lipophilic drugs.     

Effects of poly(lactic-co-glycolic acid) on preparation and characteristics of plasmid DNA-loaded solid lipid nanoparticles

Poly(lactic-co-glycolic acid) (PLGA) was used as a polymeric emulsifier to encapsulate plasmid DNA into hydrogenated castor oil (HCO)-solid lipid nanoparticles (SLN) by w/o/w double emulsion and solvent evaporation techniques. The effects of PLGA on the preparation, characteristics and transfection efficiency of DNA-loaded SLN were studied. The results showed that PLGA was essential to form the primary w/o emulsion and the stability of the emulsion was enhanced with the increase of PLGA content. DNA-loaded SLN were spherical with smooth surfaces. The SLN had a negative charge in weak acid and alkaline environment but acquired a positive charge in acidic pH and the cationisation capacity of the SLN increased with the increase of PLGA/HCO ratio. Agarose gel electrophoresis demonstrated that the majority of the DNA maintained its structural integrity after preparation and being extracted or released from DNA-loaded SLN. When PLGA/HCO ratio increased from 5 to 15%, the encapsulation efficiency, loading capacity and transfection efficiency of the nanoparticles increased significantly, whereas the changes of particle size and polydispersity index were insignificant. Cytotoxicity study in cell culture demonstrated that the SLN was not toxic.     

Physicochemical characterization techniques for solid lipid nanoparticles: principles and limitations

Solid lipid nanoparticles (SLNs) are gaining importance due to numerous advantages they offer as a drug delivery system. SLN incorporate poorly soluble drugs, proteins, biologicals, etc. SLN are prepared by techniques like high-pressure homogenization, sonication and employs a wide range of lipids and surfactants. Physicochemical characterization techniques include particle size analysis, zeta potential and determination of crystallinity/polymorphism. Furthermore, drug loading and drug entrapment efficiency are common parameters used to test the efficiency of SLN. Most importantly, the functionality assay of SLN is essential to predict the activity and performance in vivo. The review presented discusses the importance of SLN in drug delivery with emphasis on principles and limitations associated with their physicochemical characterization.     

Facile method for the preparation of the WS2 nanoparticles

A facile and simple synthetic route was proposed for the synthesis of WS2 nanoparticles. The as-prepared WS2 nanoparticles can be characterized with X-ray diffraction spectrum (XRD), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The average particle size of the product is about 85 nm that was calculated from XRD pattern by the Debye-Scherrer formula.     

Preparation and pharmacokinetic evaluation of Tashinone IIA solid lipid nanoparticles

Tashinone IIA loaded solid lipid nanoparticles (TA-SLN) coated with poloxamer 188 was prepared by emulsification/evaporation. The TA-SLN was characterized by transmission electron microscope and dynamic light scattering (DLS). The results showed that the TA-SLN had an average diameter of 98.7 nm with a zeta potential of - 31.6 mv and the drug loading of 4.6% and entrapment efficiency of 87.7%. In vitro release experiment showed that the release of Tashinone IIA from TA-SLN was in accordance with the Weibull equation. The best model fitting experimental data was a two-compartment open model with first-order. The area under curve of plasma concentration-time (AUC) and mean residence time (MRT) of TA-SLN were much higher than those of Tashinone IIA control solution (TA-SOL). The results of pharmacokinetic studies in rabbits indicated that the formulation of TA-SLN was successful in providing a delivery of slow release of Tashinone IIA.     

Effects of poly (lactic-co-glycolic acid) as a co-emulsifier on the preparation and hypoglycaemic activity of insulin-loaded solid lipid nanoparticles

Poly (lactic-co-glycolic acid) (PLGA) was used as a co-emulsifier in the preparation of insulin-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil as lipid matrix and lecithin as surfactant by doubleemulsion technique. The effects of PLGA on the preparation and hypoglycaemic activity of insulin-loaded SLN were studied. The results showed that with the supplement of PLGA, the encapsulation efficiency and loading capacity were increased significantly from 79.08±1.62 to 85.57±3.21% and 1.58±0.03 to 1.71±0.06%, whereas the surface charge and particle size were changed insignificantly from -25.87±2.65 to -22.67±1.19 mv and 431.0±16.1 to 397.0±68.0 nm, respectively. In vivo studies demonstrated that PLGA increased the sustained hypoglycaemic activity from 12 to 36 h and 24 to 120 h in normal and steptozotocin-induced diabetic mice after a single intramuscular injection of the insulin-loaded SLN. These results demonstrated that PLGA could enhance the entrapment of insulin in the nanoparticles, and more importantly, prolong the time of hypoglycaemic activity of the insulin-loaded SLN.     

Precursor solvent influence on preparation and electrochemical properties of platinum nanoparticles electrodes

The crystalline sizes and loading efficiencies of metallic nanoparticles for fuel cell catalysts have been measured by changing solvent species containing precursors. By changing the solvent species containing carbon particles and metal salt, the microstructure and the according electrochemical property of catalysts could be controlled. Four kinds of solvent were investigated in this study. Pt catalysts that were deposited on carbon blacks supports by using an ethylene glycol solution showed the highest deposition efficiency, 85% and smallest crystalline size, 2.85 nm of particles. From the experimental result, it was concluded that the electrochemical performance of catalysts was dependent on the crystalline size and deposition efficiency of metal particles, by changing solvent species.     

固体推进剂用纳米核壳型铝粉的制备及其应用研究进展

概述了国内外纳米核壳型铝粉复合材料的制备技术及其在固体推进剂中的应用研究进展,讨论了不同制备技术的优缺点以及复合粒子在应用中存在的技术难题和发展前景。     

一种制备ZnO纳米颗粒的新方法

提出了一种制备ZnO纳米颗粒的新方法。在金属钠的液氨溶液中还原硝酸锌,所形成的金属Zn自然氧化而制得ZnO颗粒。为了研究表面修饰对产物形貌、粒径和性能的影响,制备了十二烷基磺酸钠（SDS）修饰的ZnO纳米颗粒。采用X射线粉末衍射仪（XRD）、透射电子显微镜（TEM）、傅立叶变换红外光谱仪（FT-IR）、热重及差热分析仪（TG-DTA）等手段对产物进行了表征。结果表明采用该方法可制得具有六方纤锌矿结构的ZnO颗粒,未修饰ZnO颗粒团聚较为严重;修饰的ZnO纳米颗粒呈棒状,分散较好。红外和热分析表明SDS修饰在了ZnO纳米颗粒表面。测试了所制备ZnO颗粒的紫外可见吸收（UV-Vis）和光致发光（PL）谱,均出现了ZnO的特征谱带。提出的方法也适用于制备其它金属或氧化物纳米材料。     

An improved method for preparation of SrTiO3 nanoparticles

SrTiO₃ nanoparticles were synthesized for the first time via a modified polymeric precursor method. The samples were characterized by thermogravimetry, X-ray diffraction (XRD), BET surface area, micro-Raman spectroscopy, field emission scanning and transmission electron microscopy (FE-SEM and FE-STEM), high-resolution transmission electron microscopy (HRTEM) and photoluminescence measurements. It is found that calcination atmosphere (air, nitrogen and oxygen) plays an important role of both crystal size and photolumiscence behavior of the SrTiO₃ nanocrystallites. Results show that the powders obtained in nitrogen/oxygen atmosphere possess controllable particles size of approximately 11 nm presenting the highest photoluminescence emission.     

In vitro evaluation of idebenone-loaded solid lipid nanoparticles for drug delivery to the brain

Context: Solid lipid nanoparticles (SLN) are regarded as interesting drug delivery systems and their preparation techniques have gained a great deal of attention.

Objective: To evaluate the feasibility of preparing idebenone (IDE) loaded SLN from O/W microemulsions by the phase-inversion temperature (PIT) method. Since SLN have been proposed to improve drug delivery to the brain, IDE was chosen as model drug due to its activity in the treatment of neurodegenerative diseases.

Materials and Methods: Cetyl palmitate was used as solid lipid to prepare SLN containing two surfactant/cosurfactant mixtures, isoceteth-20/glyceryl oleate (SLN A) and ceteth-20/glyceryl oleate (SLN B) by the PIT method.

Results and discussion: All the formulations tested showed a mean particle diameter ranging from 30 to 95?nm and a single peak in size distribution. Stability tests showed that SLN B were more stable than SLN A. IDE release was dependent both on the type of primary surfactant used and the amount of loaded drug. IDE-loaded SLN were effective in inhibiting 2,2′-azobis-(2-amidinopropane)dihydrochloride (APPH)-induced lactic dehydrogenase (LDH) release and reactive oxygen species (ROS) production in primary cultures of astrocytes obtained from rat cerebral cortex. It is noteworthy that SLN B2 (containing ceteth-20 as primary surfactant and 0.7% w/w IDE) were able to prevent entirely both the LDH release and ROS production induced by APPH.

Conclusion: The PIT method provided SLN with good technological properties. The tested SLN could be regarded as interesting carriers to overcome the blood brain barrier and increase the efficacy of the loaded drug.     

Formulation,optimization, and characterization of rifampicin-loaded solid lipid nanoparticles for the treatment of tuberculosis

Abstract

Mycobacterium tuberculosis, being the causative infectious agent, is the leading cause of death worldwide amongst the infectious disease. The low bioavailability of rifampicin (RIF), one of the vital constituent of antitubercular therapy, instigates an urge to develop nanocarrier, which can prevent its degradation in the acidic pH of the stomach. Solid lipid nanoparticles (SLNs) have been proven to be promising versatile platform for oral delivery of lipophilic drugs. Therefore, the current investigation demonstrates development of RIF-loaded solid lipid nanoparticles (RIF-SLNs) using high-pressure homogenization technique by employing a three-level, three-factor Box–Behnken design. Concentration of drug, concentration of emulsifier, and homogenization pressure were selected as an independent variables, and %drug loading (%DL), %entrapment efficiency (%EE), and particle size were selected as dependent variables. The developed RIF-SLNs were characterized for particle size, polydispersity index, zeta potential, %EE, %DL, differential scanning calorimetry, X-ray diffraction, and TEM analysis. The mean diameter of RIF-SLNs was found to be 456?±?11?nm, %EE of 84.12?±?2.78%, and %DL of 15.68?±?1.52%. The in vitro lipolysis experiments revealed that RIF-SLNs stabilized using poloxamer 188, exhibited antilipolytic effect. Furthermore, the in vitro GI stability studies (at pH 1.2, pH 4.5, pH 6.8, and pH 7.4) revealed that the developed system could withstand various gastrointestinal tract media. The in vitro dissolution studies depicted biphasic drug release profile for drug-loaded SLNs revealing best fit with Weibull model. The accelerated stability studies for 6?months does not revealed any significant change in characteristics of developed RIF-SLNs.