liposomes filled with a dex-HEMA solution have a diameter of around 400 nm (Fig. 1, bar 1), in accordance with the size of the extrusion membrane used. After polymerizing the entrapped dex-HEMA solution by UV, the size of the particles did not alter significantly (bar 2). Adding TX100, to remove the lipid layer, did not change the size of the particles (bar 3), however, also smaller particles (∼ 12 nm) were detected (data not shown) corresponding to micelles (formed due to the removal of the lipid molecules). The aqueous solution of the naked nanogels had a relatively low level of light scattering intensity because of a low refractive index difference with water. When dextranase was added to the naked nanogels, as expected, the dex-HEMA became enzymatically degraded and nanoparticles were no longer detected (bar 4). This experiment clearly proved the existence of dextran based nanogels. When dextranase was added to the still lipid coated nanogels nanoparticles with the same size remained to exist (bar 5). This could also be expected as dextranase is not expected to permeate the lipid coating. AFM and TEM images (data not shown) revealed that the lipid coated particles were indeed surrounded by a rather rough bilayer. The naked nanogels seemed to have smooth edges, suggesting that the lipid coating has been indeed removed. DLS measurements on dex-HEMA nanogels stored in buffer at 37 °C for several days revealed that the dex-HEMA nanogels slowly degrade under physiological conditions. We revealed that for naked dex-HEMA nanogels, the degradation time clearly depends on the cross-link density of the nanogels: dex-HEMA nanogel prepared from dextran lowly substituted with HEMA degraded fast while it took days to weeks for nanogels prepared from highly substituted dextran (Fig. 2A–C). For lipid coated dex-HEMA nanogels we observed that the dex-HEMA gels in the liposomes do degrade, however, as the degradation products of the nanogels (being dextran chains and poly(HEMA)) remain encapsulated in the liposome vesicles, we remained to observe nanoparticles, even after long degradation times. The latter hypothesis was confirmed by the following experiments: lipid coated nanogels were allowed to degrade for respectively 5, 14 and 18 days. After that period TX100 was added and (besides micelles) nanoparticles were no longer detected. This proved that the nanogels in the liposomes were indeed completely degraded into a dextran and poly(HEMA) solution. Confocal laser scanning microscopy showed that lipid coated dex-HEMA nanogels (which were fluorescently labelled by adding Texas Red dextran to the nanogels) were taken up by VERO-1 cells since highly fluorescent punctuations were observed in the cytoplasm. Conclusion This study showed that biodegradable dextran nanogels, of hundreds of nanometers in size, can be obtained using liposomes as reactor. Especially, the cross-link density of the dextran nanogels clearly determines how fast the nanogels degrade (days to weeks). As dextran nanogels can be taken up by cells they may be promising vehicles for controlled intracellular drug delivery. doi:10.1016/j.jconrel.2006.09.024 008 Novel drug carrier — Chitosan gel microspheres with covalently attached nicotinic acid K. Szczubialka, K. Zomerska, A. Karewicz, M. Nowakowska Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Kraków, Poland, e-mail: karewicz@chemia.uj.edu.pl Summary Crosslinked chitosan microspheres were synthesized with nicotinic acid covalently attached through the ester bonds. Nicotinic acid (NA) was released from the microspheres in acidic aqueous suspensions. The amount and the kinetics of NA release were controlled by pH of the solution. Introduction Chitosan, a polysaccharide obtained by deacetylation of chitin, a polymer known for its biocompatibility, biodegrad- Fig. 2. Degradation profile of naked (A–C) and lipid coated (D–F) dex-HEMA nanogels. A and D: scarcely cross-linked nanogels. B and E: moderately cross- linked nanogels. C and F: highly cross-linked nanogels. e13 Abstracts