• Journal of Pharmaceutical Investigation
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• v.39 no.3
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• pp.201-205
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• 2009

Triglyceride solid lipid with medium chain fatty acid, tricaprin (TC), was used as a core matrix of lipid nanoparticles (LN) to solubilize water-insoluble paclitaxel and enhance the stability of nanoparticles by immobilization of incorporated drug in the solid core during storage at low temperature. In the present study, TC-LN containing paclitaxel was prepared by hot melt homogenization method using TC as a core lipid and phospholipids as stabilizers. The particle size of TC-LN containing paclitaxel was less than 200 nm and its zeta potential was around -40 mV. Calorimetric analysis showed TC core could be solidified by freezing and thawing in the manufacturing process in which the hot dispersion should be prepared at elevated temperature and subsequently cooled to obtain solid lipid nanoparticles. The melting transition of TC core was observed at $27.5^{\circ}C$, which was lower than melting point of TC bulk. The particle size of TC-LN remained unchanged when kept at $4^{\circ}C$. Paclitaxel containing TC-LN showed comparable anticancer activity to the Cremophore ELbased paclitaxel formulation against human ovarian (OVCAR-3) and breast (MCF-7) cancer cell lines. Thus, lipid nanoparticles with medium chain solid lipid may have a potential as alternative delivery system for parenteral administration of paclitaxel.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.452-459
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• 2017

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.63-73
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• 2010

Solid lipid nanoparticles (SLNs) have emerged to combine the advantages of polymeric nanoparticles and lipid emulsions in early 1990s. SLNs can present several desirable properties derived from the solid state core. When formulating SLNs, there should be careful considerations about the physical state of the inner solid lipid core and its polymorphism and supercooling behavior. In this review, SLNs were compared to lipid emulsion and emulsion of supercooled melt to understand the unusual behaviors compared to lipid emulsions and to have insights into stability and release mechanism. SLNs have been regarded as biocompatible system because lipids are usually well-tolerable ingredients than polymers. Several studies showed good tolerability of SLNs in terms of cytotoxicity and hemolysis. Similar to various other nanoparticulate drug delivery systems, SLNs can also change biodistribution of the incorporated drugs in a way to enhance therapeutic effect. Most of all, large scale production of SLNs was extablished wihtout using organic solvents. Although there is no SLN product in the market till date, several advantagious properties of SLNs and the progress we have seen so far would make commercial product of SLNs possible before long and encourage research community to apply SLN-based formulations for water-insoluble drugs.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.125-135
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• 1996

Solid lipid nanoparticles(SLN) are particulate systems for parenteral drug administration and suitable for controlled release. SLN were prepared by homogenization process. Dispersion at increased temperature (molten lipid) was performed to yield SLN loaded with lipophilic drugs. Tetracaine base, lidocaine base, prednisolone, methyltestosterone and ethinylestradiol were used as model drugs to access the loading capacity and to study the release behavior. To investigate production parameters(lipids, surfactant concentration, homogenizing rpm) in the formation of SLN, particle size was performed by laser diffraction analysis. The mean particle size of SLN with stearic acid or trilaurin was below 1 micron. By decreasing the particle size and increasing the surfactant concentration, the release rate was increased especially in the case of highly lipophilic drug loaded SLN. Methyltestosterone or ethinylestradiol loaded SLN showed a distinctly prolonged release over a few days.

• Journal of Dairy Science and Biotechnology
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• v.25 no.2
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• pp.5-10
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• 2007

Ultrasonication was employed to prepare solid lipid nanoparticles (SLN) for smart probiotic nanoparticles as a nanofood. The model probiotic material, lactocin from Lactobacillus plantarum (CBT-LP2), was incorporated into SLN. The CBT-LP2 loaded SLN (CBT-LP2-SLN) were spherical in the photograph of scanning electron microscope (SEM). The particle size measured by laser diffraction (LD) was found to be $97.3{\pm}8.2nm$. Zeta potential analyzer suggested the zeta potential of LP-SLN was $-29.36{\pm}3.68$ mV in distilled water. The entrapment efficiency (EE%) was determined with the sephadex gel chromatogram and high-performance liquid chromatogram (HPLC), and up to 90.59% of nanofood was incorporated. Stability evaluation showed relatively long-term stability with only slight particle growth (P>0.05) after storage at room temperature for 4 weeks. Therefore, ultrasonication is demonstrated to be a simple, available and effective method to prepare high quality SLN loaded probiotic material.

• Journal of Pharmaceutical Investigation
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• v.37 no.1
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• pp.51-55
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• 2007

Solid lipid nanoparticles (SLNs) have been regarded to behave similar to the vegetable oil emulsions because emulsions of lipid melts are formed before lipid droplets being solidified to turn into SLNs. Compared to lipid emulsion, however, it has been more difficult to obtain stable SLNs and needs more extensive considerations on stabilizer and manufacturing process. In the present study, we tried to prepare phosphatidylcholine-based trymyristin (TM) SLNs using high pressure homogenization method and optimize the manufacturing variables such as homogenization pressure, number of homogenization cycles, cooling temperature, co-stabilizer and freeze-drying with cryoprotectants. Nano-sized TM particles could be Prepared using egg Phosphatidylcholine and pegylated phospholipids ($PEG_{2000}$PE) as stabilizers. Based on the optimization study, the dispersion was manufactured by homogenization under the pressure of 100 MPa for more than 5 cycles, and solidifying the intermediately formed lipid melt droplets by dipping in liquid nitrogen followed by thawing at room temperature. In addition, TM SLNs could be freeze-dried and then redispersed easily without significant particle size changes after freeze drying with 10% and 12.5% sucrose or trehalose. The TM SLNs established in this study can be used as delivery system for drugs and cosmetics.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.39-43
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• 2010

Solid lipid nanoparticles (SLNs) were freeze-dried to obtain a stable solid dosage form with the aid of various cryoprotectants such as trehalose, sucrose, glucose, fructose, and glycerol. Tricaprin(TC) and trilaurin(TL) were used as lipid matrices for SLNs and stabilizers were egg phosphatidylcholine and pegylated phospholipid. All cryoprotectants tested did not cause changes in mean particle size of SLNs when mixed with SLNs before freeze-drying. However, the mean particle sizes of reconstituted SLNs after freeze-drying were significantly different from those of the un-lyophilized original SLN dispersions depending on the types and concentration of cryoprotectants. Although the freeze-dried SLNs without any cryoprotectants were easily reconstituted by hand-shaking, the mean particle size drastically increased (> $8\;{\mu}m$ for TC SLNs and around $1\;{\mu}m$ for TL SLNs) compared to that of un-lyophilized original dispersion (97 nm for TC SLNs and 164 nm for TL SLNs). Trehalose and sucrose were the most effective additives to protect the SLNs during lyophilization. The reconstituted SLNs were physically stable for 24 hours when lyophilized with 12.5% trehalose, sucrose, glucose, fructose or glycerol.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.33-38
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• 2005

Recently increasing attention has been focused on solid lipid nanoparticles (SLN) as a parenteral drug carrier due to its numerous advantages that can come from both polymeric particle and fat emulsions, together with the possibility of controlled release and increasing drug stability. Lipophilic drugs such as paclitaxel, cyclosporin A, and all-trans retinoic acid have been successfully entrapped in SLN but the incorporation of hydrophilic drugs in SLN is very limited because of their very low affinity to the lipid. Therefore, as a new approach to improve the loading of hydrophilic drugs, a w/o/w emulsion technique has been developed. The primary objective of the current study was to improve the loading efficiency of a model hydrophilic drug, glycine (Log P = -3.44) into SLN. The proposed preparation process is as follows: A heated aqueous phase consisting of 0.1 ml of glycine solution in water (100 mg/ml), and poloxamer 188 (5 mg) were then added to a molten oil phase containing precirol (100 mg) and lecithin (5 mg). This mixture was dispersed by sonicator, leading to a w/o emulsion. A double emulsion (w/o/w) was formed after the addition of 2% poloxamer solution to the above dispersed system. After cooling the double emulsion, solid lipid nanosuspensions were successfully formed. The lipid nanoparticles had the mean particle size of 441.25 nm, and the average zeta potential of -20.98 mV. The drug loading efficiency was measured to be 8.54% and the drug loading amount was measured to be 0.92%. The w/o/w emulsion method showed an increased loading efficiency compared to conventional o/w emulsion method.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.410.1-410.1
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• 2002

Local anesthetics are used to reduce pain. but they are so frequently injected to patients. So we prepared lidocaine solid lipid nanopaticles for long acting subcutaneous injection to decrease the number of times of injection. Solid lipid nanoparticles were prepared by spray drying method. First. drug. lipid. plasticizer and surfactant were dissolved in methylene chloride. and we operated spray dryer using this solution at setting value. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.425.2-425.2
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• 2002

The purpose of this study was to prepare thermo-sensitive solid-lipid nanoparticles (SLNs) with a lipid melted at human body temperature and to evaluate physicochemical properties of SLNs containing retinol. anti-wrinkle agent. as a model drug. SLNs were prepared using a high pressure homogenizing method. The SLNs were composed of retinol as a model drug. thermo-sensitive lipid (DS-CBS) as a lipid core. and egg phosphatidylcholine and Tween 80 as surfactants. Manufacturing variables such as homogenization pressure. (omitted)