Dual asymmetric centrifugation as an alternative preparation method for parenteral fat emulsions in preformulation development.

Nanoscaled fat emulsions are well established as a drug delivery system for lipophilic drugs and for the use in parenteral nutrition. Typically, the production of nanoscaled fat emulsions requires several formulation steps, including high pressure homogenization and filtration. The applicability of dual asymmetric centrifugation as an alternative technique to produce submicron fat emulsions in a short and easy way was investigated. The emulsions could be prepared without substance loss in a closed system within 30 min. Formulations with 10% soybean oil and up to 5% emulsifier-mixture were produced. The droplet size distribution was determined by static light scattering. Stability over six months was shown by regular static light scattering measurements and determination of the zeta potential. Furthermore, hemolytic activity of the samples was investigated. With the dual asymmetric centrifugation physiological tolerable emulsions with droplets in the lower micron and submicron range could be prepared. This method could be used as a model for screening active pharmaceutical ingredients.

Tumor accumulation of NIR fluorescent PEG-PLA nanoparticles: impact of particle size and human xenograft tumor model.

Cancer therapies are often terminated due to serious side effects of the drugs. The cause is the nonspecific distribution of chemotherapeutic agents to both cancerous and normal cells. Therefore, drug carriers which deliver their toxic cargo specific to cancer cells are needed. Size is one key parameter for the nanoparticle accumulation in tumor tissues. In the present study the influence of the size of biodegradable nanoparticles was investigated in detail, combining in vivo and ex vivo analysis with comprehensive particle size characterizations. Polyethylene glycol-polyesters poly(lactide) block polymers were synthesized and used for the production of three defined, stable, and nontoxic near-infrared (NIR) dye-loaded nanoparticle batches. Size analysis based on asymmetrical field flow field fractionation coupled with multiangle laser light scattering and photon correlation spectroscopy (PCS) revealed narrow size distribution and permitted accurate size evaluations. Furthermore, this study demonstrates the constraints of particle size data only obtained by PCS. By the multispectral analysis of the Maestro in vivo imaging system the in vivo fate of the nanoparticles next to their accumulation in special red fluorescent DsRed2 expressing HT29 xenografts could be followed. This simultaneous imaging in addition to confocal microscopy studies revealed information about the accumulation characteristics of nanoparticles inside the tumor tissues. This knowledge was further combined with extended size-dependent fluorescence imaging studies at two different xenograft tumor types, the HT29 (colorectal carcinoma) and the A2780 (ovarian carcinoma) cell lines. The combination of two different size measurement methods allowed the characterization of the dependence of nanoparticle accumulation in the tumor on even rather small differences in the nanoparticle size. While two nanoparticle batches (111 and 141 nm in diameter) accumulated efficiently in the human xenograft tumor tissue, the slightly bigger nanoparticles (diameter 166 nm) were rapidly eliminated by the liver.