Progress in research and application of PLGA embolic microspheres.

Transcatheter arterial chemoembolization was an important method in the treatment of solid cancers and the effectiveness of such treatment depends on the nature of embolic agent. Due to the biocompatibility, controllable degradation rate, and both hydrophobicity-hydrophilicity, researches of application on poly(lactic-co-glycolic acid) (PLGA) in medical practice has been ongoing for more than 40 years. We have seen many benefits for patients in recent years. There were five different methods of preparing micrometer-scale microspheres, and three kinds of PLGA microspheres have been subjected to experimental research or used in clinical applications, namely blank microspheres, drug-loaded microspheres, and radioactive microspheres. Hereby, we reviewed the production and clinical and experimental applications of PLGA microspheres in practice.

PLGA microspheres by Supercritical Emulsion Extraction: a study on insulin release in myoblast culture.

Supercritical Emulsion Extraction in a Continuous operation layout is proposed for the production of poly-lactic-co-glycolic acid (PLGA) microspheres loaded with insulin, selected as a model of bioactive signal. Microspheres with different mean sizes of 2 µm (±0.9 µm) and 3 µm (±2.2 µm) and insulin loadings of 3 and 6 mg/g were obtained by processing different water-oil-water emulsions; an encapsulation efficiency of about 60% w/w was measured in all cases. Insulin release profiles from PLGA microspheres were also characterized in two different media (Phosphate-Buffered Saline and Dulbecco's Modified Eagle Medium) and kinetic constants were estimated by using a model proposed in literature. The produced microspheres were, then, used for the cultivation of rat embryonic ventricular myoblasts in a serum-free medium to monitor the biological effect of the released insulin. The best cell viability and proliferation, supported by released insulin, was monitored when microspheres with mean size of 3 µm loaded with 3 mg/g of insulin were added.

Continuous supercritical emulsions extraction: a new technology for biopolymer microparticles production.

Supercritical emulsion extraction (SEE) was recently proposed for the production of biopolymer microparticles starting from oil-in-water emulsions. This technology can improve the product quality because of the fast and selective extraction of the dispersed oily phase by using supercritical carbon dioxide (SC-CO(2) ). However, until now, SEE was proposed in batch configuration, sharing with the traditional processes an intrinsically discontinuous operation and problems of batches reproducibility and process yield. In this study, by using a countercurrent packed column, the SEE process was proposed in a continuous operating mode (SEE-CM) for the production of poly-lactic-co-glycolic acid (PLGA) microparticles. The new process design takes advantage of the large contact area between the SC-CO(2) and emulsion allowing the production of PLGA microparticles with controlled and narrow size distributions in only few minutes. SEE-CM operating parameters such as pressure, temperature, and flow rate ratios were analyzed and the process efficiency in terms of recovered material and its size distribution compared with SEE (batch mode operation) and conventional evaporation technology. PLGA microparticles showed a mean particle size between 1-3 µm (depending on the droplet sizes) with a SD that was always smaller than that associated with particles produced by discontinuous processes. Single and double emulsions were successfully treated and the microparticles physico-chemical properties showed no morphological and structural differences between the SEE-CM-produced microparticles and the ones obtained by conventional evaporation technology.

Novel tubular composite matrix for bone repair.

Tissue engineering develops organ replacements to overcome the limitations associated with autografts and allografts. The work presented here details the development of biodegradable, porous, three-dimensional polymer-ceramic-sintered microsphere matrices to support bone regeneration. Poly(lactide-co-glycolide)/hydroxyapatite microspheres were formed using solvent evaporation technique. Individual microspheres were placed in a cylindrical mold and sintered at various temperatures. Scaffolds were characterized using scanning electron microscopy, mercury porosimetry, and mechanical testing in compression. After varying the temperature of sintering, a single temperature was selected and the time of sintering was varied. Mechanical testing indicated that as the sintering temperature or time was increased, the elastic modulus, compressive strength, maximum compressive load, and energy at failure significantly increased. Furthermore, increasing the sintering temperature or time resulted in a decreased porosity and the spherical morphology of the microspheres was lost as the microspheres blended together. To more closely mimic the bone marrow cavity observed in native bone tissue, tubular composite-sintered microsphere matrices were formed. These scaffolds demonstrated no statistically significant difference in compressive mechanical properties when compared with cylindrical composite-sintered microsphere matrices of the same dimension. One potential application for these scaffolds is bone regeneration.

Degradability and sediment sorption of an alcohol polyglycol ether surfactant putatively useful for the control of red swamp crayfish in rice fields.

This work reports studies of the degradation rates of a fatty alcohol polyglycol ether non-ionic surfactant, Genapol OXD-080, putatively useful for the control of red swamp crayfish (Procambarus clarkii Girard) in rice fields under laboratory and field conditions. The influence of temperature, sediment site specificity and sorption were taken into account. The degradation kinetics of the surfactant depends on the experimental conditions: type of inocula and temperature. The distribution of this chemical in aquatic systems was also examined. Genapol OXD-080 was removed into the sediments readily after application, and sorption was considered the major path of removal from the water phase. Data suggest that further studies are required regarding the effects of Genapol OXD-080 in aquatic organisms resident in rice fields, in parallel with the development of technologies related with the use of surfactants to control P. clarkii populations.

Preparation of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams by use of ice microparticulates.

Biodegradable foams of poly(L-lactic acid) (PLLA) and poly(DL-lactic-co-glycolic acid) (PLGA) for tissue engineering were fabricated by a porogen-leaching technique using ice microparticulates as the porogen material. PLLA or PLGA solution in chloroform was mixed with ice microparticulates. The mixtures were frozen by being placed in molds in liquid nitrogen and freeze-dried to form the foams. Scanning electron microscopic observation of the PLLA and PLGA foams showed that evenly distributed and interconnected pore structures were formed in these foams. The porosity and surface area of the foams increased with an increase in the weight fraction of the ice microparticulates, while the median pore size remained unchanged. The pore structures of the foams could be manipulated by controlling processing variables such as the size and weight fraction of the ice microparticulates and polymer concentration.

Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation.

Poly(L-lactic acid) and its copolymers with D-lactic and glycolic acid were used to fabricate various porous biodegradable scaffolds suitable for tissue engineering and drug delivery based on a thermally induced phase separation (TIPS) technique. A variety of parameters involved in TIPS process, such as types of polymers, polymer concentration, solvent/nonsolvent ratio, and quenching temperature, were examined in detail to produce a wide array of micro- and macroporous structures. A mixture of dioxane and water was used for a binary composition of solvent and nonsolvent, respectively. In particular, the coarsening effect of pore enlargement affected by controlling the quenching temperature was used for the generation of a macroporous open cellular structure with pore diameters above 100 microm. The use of amorphous polymers with a slow cooling rate resulted in a macroporous open cellular structure, whereas that of semicrystalline polymers with a fast cooling rate generated a microporous closed cellular structure. The fabricated porous devices loaded with recombinant human growth hormone (rhGH) were tested for the controlled delivery of rhGH, as a potential additional means to cell delivery.

Effect of preparative variables on the properties of poly(dl-lactide-co-glycolide)-methoxypoly(ethyleneglycol) copolymers related to their application in controlled drug delivery.

The effect of certain preparative variables, such as the composition of the feed, the reaction time and the reaction temperature, on the properties of prepared poly(dl-lactide-co-glycolide)-methoxypoly(ethyleneg lycol) (PLGA-mPEG) copolymers and on the yield of the reaction was investigated. The results with regard the molecular weight and yield were discussed in relation to a polymerization mechanism proposed recently (Du et al., 1995. Macromolecules 28, 2124-2132). The higher the PEG content of the feed the lower the molecular weight of the copolymer and the yield of the reaction. The breadth of the molecular weight distribution decreased initially with time, but appeared to stabilize later at low values. Both the ethylene oxide content and the lactide to glycolide molar ratio in the copolymer depended on the reaction temperature and varied with the reaction time. PLGA and mPEG appeared to be partially miscible, and copolymers containing approximately 40% mol or higher ethylene oxide exhibited crystallinity.