(1/2854) In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel.

Paclitaxel (Taxol), a diterpenoid isolated from Taxus brevifolia, is effective against several murine tumors, and is one of the most exciting anticancer molecules currently available. Due to its low solubility in water, it is clinically administered with polyethoxylated castor oil (Cremophor EL), which causes serious side effects. Inclusion of paclitaxel in solid lipid nanoparticles (SLNs) has proved to be a good approach to eliminate the need for Cremophor EL and improve the drug's antitumor efficacy. This paper describes the development of two types of long-circulating SLNs as colloidal carriers for paclitaxel. SLNs are constituted mainly of bioacceptable and biodegradable lipids. In vitro release kinetics showed that the release was very slow, the release of paclitaxel from F68-SLN is linear, and the release of paclitaxel from Brij78-SLN followed the Weibull equation. Pharmacokinetics was evaluated in KM mice after injection of paclitaxel formulated in Cremophor EL or in Brij78-SLN and F68-SLN. Encapsulation of paclitaxel in both SLNs produced marked differences compared with the free drug pharmacokinetics. F68-SLN and Brij78-SLN are long-circulating (t 1/2 beta, 10.06 and 4.88 h, respectively) compared with paclitaxel injection (t 1/2 beta, 1.36 h).  (+info)

(2/2854) Uptake of cyclosporine A loaded colloidal drug carriers by mouse peritoneal macrophages in vitro.

AIM: To investigate the uptake of cyclosporine A loaded colloidal drug carriers by mouse peritoneal macrophage (MPM) in vitro. METHODS: The [3H]cyclosporine A loaded colloidal particles: polylactic acid nanospheres, polylactic acid nanocapsules, and microemulsions were prepared. The [3H]cyclosporine A loaded colloidal particles were incubated with MPM for 30 min at 37 degrees C, then the cells were separated from the colloidal particles and the radioactivity was measured by a liquid scintillation counter. RESULTS: In comparison to the cyclosporine A solution, the binding to polylactic acid nanospheres produced a 20-fold increase in the uptake of cyclosporine A by MPM in 30 min incubation, whereas some obvious decrease in the uptake of cyclosporine A by MPM was observed in the binding of cyclosporine A with polylactic acid nanocapsules or microemulsions. The surfactant coating and plasma protein adsorption were found to have marked effects on the uptake of cyclosporine A loaded nanospheres by MPM. CONCLUSION: Our present study indicated that colloidal drug carriers might affect the targeting of cyclosporine A to mononuclear phagocyte system.  (+info)

(3/2854) PEGylated polycyanoacrylate nanoparticles as salvicine carriers: synthesis, preparation, and in vitro characterization.

AIM: To synthesized poly(methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEGylated PHDCA) with polyethylene glycol (PEG, Mr = 5000), prepare PEGylated PHDCA and poly(n-hexadecyl cyanoacrylate) (PHDCA) nanoparticles loading salvicine and determine their in vitro characterizations. METHODS: The structure of PEGylated PHDCA was determined with 1H-NMR, 13C-NMR and Fourier transform infrared spectrum (FTIR). Its molecular weight was determined by gel permeation chromatography (GPC). Nanoparticles were prepared by emulsion/solvent evaporation method. RESULTS: 1H-NMR, 13C-NMR, and FTIR were consistent with structure of PEGylated PHDCA, whose average molecular weight is 6680. Entrapment efficiency could be determined by high pressure liquid chromatography (HPLC) method without endogenous interference at the retention time of salvicine. The entrapment efficiency was 92.6 % for PEGylated PHDCA nanoparticles and 98.9 % for PHDCA nanoparticles. The nanoparticles size was about 250 nm. The values of the zeta potential were obviously influenced by the composition of the copolymer. Compared with PHDCA nanoparticles (-23.1 mV), PEGylated PHDCA nanoparticles showed a low surface potential (-9.6 mV). Salvicine release from nanoparticles showed an initial burst effect, then a plateau for an extended period, and finally sustained release phase. CONCLUSION: These results showed that the PEGylated PHDCA nanoparticles could be an effective carrier for salvicine delivery in the respect of anti-tumor potency.  (+info)

(4/2854) In vitro and in vivo evaluation of oral heparin-loaded polymeric nanoparticles in rabbits.

BACKGROUND: Owing to its short half-life and lack of oral absorption, heparin has to be administered by the parenteral route. An oral heparin formulation, however, would avoid the disadvantages of parenteral injections and would consequently be highly desirable for patients. Polymeric nanoparticles (NPs) prepared with biodegradable poly-epsilon-caprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) and nonbiodegradable positively charged polymers (Eudragit RS and RL), used alone or in combination, were evaluated in vitro and in vivo after a single oral administration of heparin-loaded NPs in rabbits. METHODS AND RESULTS: After oral administration of heparin-loaded NPs in rabbits (600 IU/kg), increases in both anti-factor Xa activity and activated partial thromboplastin time (aPTT) were detected with each formulation. Moreover, the anti-Xa activity was detected for a longer period than when a heparin solution was administered intravenously. A peak concentration of 0.16+/-0.01 IU/mL and an average aPTT of 24 seconds (2-fold increase) were obtained 7 hours after oral dosing of Eudragit RL/PCL NPs containing heparin, exhibiting an absolute bioavailability of 23%. CONCLUSIONS: The significant increases in anti-factor Xa activity and aPTT confirmed the oral absorption in rabbits of heparin released from polymeric NPs.  (+info)

(5/2854) Protein nanoarrays generated by dip-pen nanolithography.

Dip-pen nanolithography was used to construct arrays of proteins with 100- to 350-nanometer features. These nanoarrays exhibit almost no detectable nonspecific binding of proteins to their passivated portions even in complex mixtures of proteins, and therefore provide the opportunity to study a variety of surface-mediated biological recognition processes. For example, reactions involving the protein features and antigens in complex solutions can be screened easily by atomic force microscopy. As further proof-of-concept, these arrays were used to study cellular adhesion at the submicrometer scale.  (+info)

(6/2854) Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo.

Low efficiencies of nonviral gene vectors, the receptor-dependent host tropism of adenoviral or low titers of retroviral vectors limit their utility in gene therapy. To overcome these deficiencies, we associated gene vectors with superparamagnetic nanoparticles and targeted gene delivery by application of a magnetic field. This potentiated the efficacy of any vector up to several hundred-fold, allowed reduction of the duration of gene delivery to minutes, extended the host tropism of adenoviral vectors to nonpermissive cells and compensated for low retroviral titer. More importantly, the high transduction efficiency observed in vitro was reproduced in vivo with magnetic field-guided local transfection in the gastrointestinal tract and in blood vessels. Magnetofection provides a novel tool for high throughput gene screening in vitro and can help to overcome fundamental limitations to gene therapy in vivo.  (+info)

(7/2854) Array-based electrical detection of DNA with nanoparticle probes.

A DNA array detection method is reported in which the binding of oligonucleotides functionalized with gold nanoparticles leads to conductivity changes associated with target-probe binding events. The binding events localize gold nanoparticles in an electrode gap; silver deposition facilitated by these nanoparticles bridges the gap and leads to readily measurable conductivity changes. An unusual salt concentration-dependent hybridization behavior associated with these nanoparticle probes was exploited to achieve selectivity without a thermal-stringency wash. Using this method, we have detected target DNA at concentrations as low as 500 femtomolar with a point mutation selectivity factor of approximately 100,000:1.  (+info)

(8/2854) Micro/nano encapsulation via electrified coaxial liquid jets.

We report a method to generate steady coaxial jets of immiscible liquids with diameters in the range of micrometer/nanometer size. This compound jet is generated by the action of electro-hydrodynamic (EHD) forces with a diameter that ranges from tens of nanometers to tens of micrometers. The eventual jet breakup results in an aerosol of monodisperse compound droplets with the outer liquid surrounding or encapsulating the inner one. Following this approach, we have produced monodisperse capsules with diameters varying between 10 and 0.15 micrometers, depending on the running parameters.  (+info)