Magnetic targeting after femoral artery administration and biocompatibility assessment of superparamagnetic iron oxide nanoparticles.

Ferrofluids are attractive candidates for magnetic targeting system because of their fluidity and magnetism. The magnetic nanoparticles in ferrofluids should have combined properties of superparamagnetic behavior, target localization, and biocompatibility. The magnetic targeting and biocompatibility of superparamagnetic iron oxide nanoparticles stabilized by alginate (SPION-alginate) was investigated in vitro and in vivo. The localization of SPION-alginate by an external magnetic field in vitro was quantitatively evaluated by determining the iron content, and the results revealed that the localization ratio of SPION-alginate was 56%. Magnetic targeting of the SPION-alginate after femoral artery administration with the magnetic field in rats was quantitatively investigated by iron content and qualitatively confirmed by histological evaluation and magnetic resonance imaging. The ratio of iron content between the target site and the nontarget site were 8.88 at 0.5 h and 7.50 at 2 h, respectively. The viability of RAW264.7 cells and L929 cells was apparently unaltered upon exposure to SPION-alginate. The incubation with erythrocytes indicated that the SPION-alginate did not induce erythrocytes hemolysis and aggregation. In conclusions, the SPION-alginate had magnetic targeting with an external magnetic field and did not be detained at the injection site without the magnetic field. The SPION-alginate was generally considered to be biocompatible in cytotoxicity and hemolysis aspects.

Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle-mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells.

Optimal gene therapy for tumors must deliver DNA to tumor cells with high efficiency and minimal toxicity. It has been reported that in non-viral gene delivery, the hydroxyethyl group at the amino terminal in cationic lipid was important for high transfection efficiency. Therefore, in this study, we developed new cationic nanoparticles (NP-OH) composed of cholesteryl-3beta-carboxyamidoethylene-N-hydroxyethylamine and Tween 80, and optimized in vitro and in vivo transfections for potential use as a non-viral DNA vector into human prostate tumor PC-3 cells and xenografts. In vitro transfection resulted in efficient DNA transfer when positive-charged nanoplex was prepared in the presence of sodium chloride (NaCl). In in vivo transfection, negative-charged nanoplex formed in water strongly induced the gene expression compared with positive-charged nanoplex when directly transfected into xenografts. These transfection efficiencies in vitro and in vivo were comparable to each commercial product. Furthermore, NP-OH nanoplexes displayed no induction of tumor necrosis factor (TNF)-alpha when administered by intravenous injection. The results of the experiments provided optimal conditions to form NP-OH nanoplex for gene delivery in vitro and in vivo. NP-OH is a potential non-viral DNA vector for the local treatment of tumor and in vitro.

Pharmacokinetics and pharmacodynamics of sterylglucoside-modified liposomes for levonorgestrel delivery via nasal route.

For emergency contraceptive, the rapid delivery of levonorgestrel (LNG) to plasma is desirable, furthermore, a sustained delivery of LNG along with rapid absorption will be necessary. The pharmacokinetics and pharmacodynamics of LNG entrapped in different kinds of liposome formulations via nasal administration in rats were evaluated and compared with LNG suspension via the oral route. The relative bioavailabilities of these liposome formulations via nasal administration were 100% or higher than 100%. The Cmax and Tmax values of sterylglucoside (SG) and chitosan-contained formulations by nasal administration were 416.84 ng/mL and 1.02 hr, 227.97 ng/mL and 2.02 hr, respectively, compared with that of 334.94 ng/mL and 1.89 hr of oral suspension. Fully 100% contraception was observed for all the formulations. SG could promote the absorption of LNG via the nasal route and may provide a rapid onset of action of LNG for emergency contraception. Chitosan could retain LNG in the nasal cavity for long contact time to sustain delivery of LNG. The rapid onset and sustained delivery of LNG can be achieved via the nasal route using liposomes as the vehicle.

[Cholesteryl hemisuccinate as liposomal membrane stabilizer and its use in the preparation of saikosaponin-D liposomes].

AIM: To study the membrane stabilization effect and mechanism of cholesteryl hemisuccinate (CHEMS) on dipalmitoylphosphatidylcholine (DPPC) liposomes; Saikosaponin-D (SSD) liposomes were prepared by using CHEMS as a membrane stabilizer and its encapsulation efficiency and hemolytic activity were evaluated. METHODS: Differential scanning calorimetry (DSC) and calcein release were used to study membrane stabilization effect of CHEMS on DPPC membrane, Fourier transform infrared spectroscopy (FT-IR) was used to study the interacting mechanism of CHEMS with DPPC, sedimentation experiment was done to study the interaction of CHEMS with SSD and hemolytic study was used to evaluate the hemolytic activity of SSD-liposomes with CHEMS as membrane stabilizer. RESULTS: DSC analysis showed that CHEMS and cholesterol (CHOL) could all decrease the Tm value slightly and the deltaH value markedly. CHEMS was more effective than CHOL in decreasing the deltaH value of DPPC membrane. It suggested that CHEMS was more effective in increasing DPPC membrane stability. It was also proved by calcein release study carried out both in PBS and 30% plasma. The findings by FT-IR suggested that CHEMS has both hydrogen bond and electrostatic interaction with the polar head of DPPC. CHEMS did not form insoluble complex (INCOM) with SSD by sedimentation experiment. Stable SSD-liposomes were prepared using DPPC and CHEMS and decreased effectively the hemolytic activity of SSD, SSD-liposomes may be given intravenously at a concentration of 15 microg x mL(-1), while free SSD was forbidden to be given intravenously. CONCLUSION: CHEMS was more effective than CHOL in increasing DPPC membrane stability, and it could be of great use in the preparation of cholesterol-dependent hemolytic saponins-liposomes. The hemolytic activity of SSD-liposomes was greatly reduced, allowing a possible concentration of 15 microg x mL(-1) to be intravenously administered.

Cholesteryl hemisuccinate as a membrane stabilizer in dipalmitoylphosphatidylcholine liposomes containing saikosaponin-d.

In the present study, cholesteryl hemisuccinate (CHEMS) was evaluated for use as a membrane stabilizer in dipalmitoylphosphatidylcholine (DPPC) liposomes. Differential scanning calorimetry (DSC) and a calcein release study showed that CHEMS was more effective than cholesterol (CHOL) in increasing DPPC membrane stability. The findings of Fourier transform infrared spectroscopy (FT-IR) also suggested that CHEMS interacts with DPPC via both hydrogen bonding and electrostatic interaction. More importantly, CHEMS did not interact with saikosaponin-d (SSD), a triterpene saponin from Bupleurum species, unlike CHOL. SSD-containing liposomes with DPPC, CHEMS and DSPE-PEG could greatly decrease the hemolytic activity of SSD. This study demonstrated that CHEMS has more stabilization ability than CHOL since CHEMS may exhibit both hydrogen bond interaction and electrostatic interaction with DPPC membrane while CHOL only has hydrogen bond interaction, resulting in stable and low-hemolytic SSD-liposomes.

[Studies on pulsatile release tablets of diltiazem hydrochloride in explosion way].

AIM: To investigate the preparation of pulsatile release tablets, the release of the drug in vitro and the pharmacokinetics in vivo. METHODS: Diltiazem hydrochloride (DIL) was used as model drug. The pulsatile release tablets were prepared by film-coated method using ethylcellulose and Eudragit L. The effect of formulation on pulsatile release of diltiazem hydrochloride was investigated under release rate test. The mechanism of pulsatile release of drug was proved by the test of water-uptake. The pharmacokinetic and bioavailability study in eight human subjects was performed by HPLC method. RESULTS: The release of diltiazem hydrochloride effected by the formulation of the core tablets and the composition and thickness of the coating film. In vitro, the delayed-release time T10 was 4.4 h, the maximum release time Trm was 8.0 h and the pulsed-release time Trm-10 was 3.6 h. In vivo, the delayed-release time Tlag was 4.9 h, the peak time was 8.0 h and the pulsed-release time was 3.1 h. The relative bioavailability was 105%. CONCLUSION: The release of drug from pulsatile release tablets of diltiazem hydrochloride was shown to be in pulsed way both in vitro and in vivo.