Liposome retention in size exclusion chromatography

BACKGROUND: Size exclusion chromatography is the method of choice for separating free from liposome-encapsulated molecules. However, if the column is not presaturated with lipids this type of chromatography causes a significant loss of lipid material. To date, the mechanism of lipid retention is poorly understood. It has been speculated that lipid binds to the column material or the entire liposome is entrapped inside the void. RESULTS: Here we show that intact liposomes and their contents are retained in the exclusion gel. Retention depends on the pore size, the smaller the pores, the higher the retention. Retained liposomes are not tightly fixed to the beads and are slowly released from the gels upon direct or inverted eluent flow, long washing steps or column repacking. Further addition of free liposomes leads to the elution of part of the gel-trapped liposomes, showing that the retention is transitory. Trapping reversibility should be related to a mechanism of partitioning of the liposomes between the stationary phase, water-swelled polymeric gel, and the mobile aqueous phase. CONCLUSION: Retention of liposomes by size exclusion gels is a dynamic and reversible process, which should be accounted for to control lipid loss and sample contamination during chromatography

THE USE OF MINIPIG IN DRUG DISCOVERY AND DEVELOPMENT; Pros and cons of minipig selection and strategies to use as a preferred non-rodent species

The pig has been introduced more than 20 years ago in drug development following attempts of finding a species which shares better homology with human than the dog based on bio-physiological parameters. However, miniaturization, standardized breeding and health status control were required before the pig could find a broader than niche application in pharmaceutical industry. During the years of experience with minipigs in pharmaceutical research and the science evolving rapidly, the selection of a non-rodent animal species for preclinical safety testing became primarily driven by pharmacological (target expression homologous function), pharmacokinetic and bio-physiological considerations. This offered a broad field of application for the minipig, besides the well-established use in dermal projects in all areas of drug development but also in novel approaches including genetically modified animals. In this article we look at recent approaches and requirements in the optimal selection of a non-rodent model in pharmaceutical development and critically ask how good of a choice the minipig offers for the scientist, how did the testing environment evolve and what are the key requirements for a broader use of the minipig compared to the other well established non-rodent species like dog or monke

Nanocapsules fonctionnalisées

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Hybrid nanocapsules: Interactions of ABA block copolymers with liposomes

Amphiphilic ABA triblock copolymers, such as poly(2-methyloxazoline)-block-poly(dimethylsiloxan)-block-poly(2-methyloxazoline) (PMOXA-PDMS-PMOXA), form vesicular structures. Here, the interaction of these ABA molecules with lipids is investigated by electron microscopy, fluorescence spectroscopy, light scattering, and differential scanning calorimetry. Our observations suggest the formation of homogeneous mixed polymerâˆ'lipid composites, independent of preparation method, i.e. film hydration, dispersion, or detergent removal. When ABA polymersomes and liposomes are mixed, we observed monomer exchanges on a time scale of minutes. The possibility of forming mixed structures and the exchanges between preformed structures allow the combination of the properties of lipids and polymers such as stability and loading encapsulation capacity

Microstructured Liposome Array

International audienc