The development of biomaterials to treat, repair, or reconstruct the human body is an increasingly important component of materials research. Collaboration between materials researchers and their industrial and clinical partners is essential for the development of this complex field. To demonstrate the importance of these interactions, two articles in this issue focus on advances in biomaterials relating to the use of colloidal systems for transport, drug delivery, and other medical applications. These articles were coordinated by Dominique Muster (Université Louis Pasteur, Strasbourg) and Franz Burny (Hôpital Erasme, Brussels). The following is the second of these two articles.
Biodegradable poly(lactide-co-glycolide) (PLGA) nanospheres in the size range 80–150 nm have been produced, using an interfacial polymer deposition (nanoprecipitation) method. The nanospheres have been surface modified with poly(ethylene glycol) (PEG) either by adsorption of polypropylene oxide-polyethylene oxide (PPO-PEO) block copolymers of the poloxamer and poloxamine series (poloxamer 407, poloxamine 904 and poloxamine 908) or by incorporation of the same copolymers into the nanospheres during the production. The nanospheres were radiolabelled by incorporation of indium-111-oxine during nanosphere production. The biological behaviour of the PLGA nanosphere systems is discussed in terms of the in vitro cell interaction with isolated non-parenchymal liver cells and the in vivo biodistribution in the rat and rabbit models after intravenous injection. The results are compared to those for model polystyrene nanospheres surface modified in the same manner. It is shown that PLGA nanospheres coated with poloxamer 407 or poloxamine 908 exhibit prolonged blood circulation times accompanied by a combined reduction in liver and spleen accumulation after intravenous injection to the rat. Three hours post intravenous injection, 39% and 28% of the administered dose of poloxamer 407- and poloxamine 908-coated PLGA nanospheres remains in the blood circulation.
Copolymers of polylactide and poly(ethylene glycol) (PLA-PEG), which self-disperse in water to form spherical nonionic micelles, have been investigated as a novel biodegradable drug delivery system. These copolymers are defined by the molecular weight ratios of their polylactide to poly(ethylene glycol) components (1.5:2 PLA-PEG and 2:5 PLA-PEG) and gave two peaks when purified by gel permeation chromatography (GPC). The first peak consisted of spherical micelles with a diameter of 15.6 nm for 1.5:2 PLA-PEG, and 18.9 nm for 2:5 PLA-PEG micelles after analysis by dynamic light scattering (DLS) and by transmission electron microscopy (TEM). The second peak was a PLA-depleted species resulting from the synthesis and did not form micelles. Testosterone and sudan black B (SBB), which have different hydrophobicities, were used as ''model drugs'' to evaluate the drug loading ability of the micelles. Ultracentrifugation sedimentation velocity studies confirmed that solubilization of the model drugs had occurred by micellar incorporation. Higher drug loading was obtained for the 1.5:2 PLA-PEG micelles (63.9% (w/w) of SBB, 0.74% (w/w) of testosterone) than for the 2:5 PLA-PEG micelles (59.0% (w/w) of SBB, 0.34% (w/w) of testosterone). The amount of testosterone solubilized was therefore significantly lower than SBB for both copolymers. Stability testing in the presence of salt suggested that the micelles had sterically stabilized surfaces. In vivo studies in the rat, using a radioactive marker, showed that PLA-PEG micelles demonstrated extended circulation times in the blood during the period of study (3 h). The 1.5:2 PLA-PEG showed increased blood levels and lower uptake of the micelles by the liver compared to the 2:5 PLA-PEG micelles. This is thought to be due to differences in the packing density of the copolymer molecules on the micelle surface.
Coal organic microspheres (COM), a novel material originated from the organic components of coal, were obtained from brown coal directly using a one-step treatment in a flow of water. Here, we studied in detail the effect of hydrothermal conditions on morphology, yield, elemental composition, functional groups, and molecular composition of COM, at temperatures of 250, 300, 350, and 380 °C, pressures of 4, 10, 20, and 24 MPa, and holding times of 0, 30, 60, and 90 min. The holding time influences COM production: longer holding time leads to higher yields and larger particle size. The hydrothermal temperature and pressure, which control the properties of water, have a significant influence on the yield, shape, and particle size of COM. The properties of water affect the COM yields as follows: 1) when the phase of water is liquid, the lower density, viscosity, and static dielectric constant gives higher yields; 2) the yield obtained in supercritical water is higher than that in subcritical water; 3) phase transformation of water from liquid to gas decreases the yield. Additionally, the particle size of COM can be controlled by the temperature, and the pressure affects the shape of COM greatly; even nano-sized particles are produced at 350 °C and 10 MPa. From the molecular composition results, low-molecular weight compounds with small double bond equivalents decompose under supercritical water condition. Large amounts of organic compounds in brown coal are thermally decomposed and extracted under hydrothermal conditions, and then spherical COM particles form and grow from small to big during the cooling process. These results are helpful for clarifying the formation mechanism of COM, and enable control of COM yield and properties.