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

• Biotechnology and Bioprocess Engineering:BBE
• /
• v.6 no.4
• /
• pp.284-288
• /
• 2001

Lipid emulsions with saturated triacylglycerols (TAGs) with 4 to 10 carbons in each acyl chain were prepared to study how the oil component alters the stability of the lipid emul-sions when phosphatidylcholines were used as emulsifiers. The average droplet size of the emul-sions became smaller as the chain length of the TAG increased. For a given oil emulsion with smaller droplets was formed with an emulsifier having higher HLB value. The influence of HLB values on the droplet size was biggest for the tributyrin (C4) emulsion. For the tricaprylin(C8) emulsions, droplet size was identical at given emulsifier concentrations regardless of HLB values. The HLB value and the concentration of the emulsifiers also affect the droplet size of the emul-sions. The emulsions with smaller average droplet size were more stable than with bigger size for 20 days. The oil and water (o/w) interfacial tension in inversely proportional to the initial droplet size of the emulsion.

• Journal of Pharmaceutical Investigation
• /
• v.40 no.1
• /
• pp.39-43
• /
• 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 Microbiology and Biotechnology
• /
• v.10 no.6
• /
• pp.764-769
• /
• 2000

The lipase gene(lip) from Bacillus stearothermophilus was recombined in vitro by utilizing the DNA shuffling technique. After four rounds of shuffling, transformation, and screening based on the initial rate of clear zone formation on a tricaprylin plate, a clone (M10) was isolated, the cell extract of which showed about 2.8-fold increased lipase activity. The DNA sequence of the mutant lipase gene (m10) showed 3 base changes, resulting in two cryptic mutations and one amino acid substitution: S113($AGC{\rightarrow}AGT$), L252 ($TTG{\rightarrow}TTA$), and G275E ($GGA{\rightarrow}GAA$). SDS-PAGE analysis revealed that the increased enzyme activity observed in M10 was partly caused by high expression of the m10 lipase gene. The amount of the expressed G275E lipase was estimated to comprise as much as 41% of the total soluble proteins of the cell. The maximum velocity ($V_{max}$) of the purified mutant enzyme for the hydrolysis of olive oil was measured to be 3,200 U/mg, which was 10% higher than that of the parental (WT) lipase (2,900 U/mg). Its optimum temperature for the hydrolysis of olive oil was $68^{\circ}C$ and it showed a typical $Ca^{2+}$-dependent thermostability, properties fo which were the same as those of the WT lipase. However, the mutant enzyme exhibited a high enantiospecificity towards (S)-naproxen compared with the WT lipase. In addition, it showed increased hydrolytic activity towards triolein, tricaprin, tricaprylin, and tricaproin.