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A hydrochemical investigation was conducted in northwest margin of Lop Nur to evaluate the groundwater chemical patterns and the main hydrological processes occurring in the groundwater system. Fourteen representative groundwater samples were collected from different springs and boreholes. Hydrochemical data of the groundwater showed that SO4, Cl-Na and Cl, SO4-Na water types were dominant in this area, and the total dissolved solid (TDS) content rose along the flow path of the groundwater. Ionic relation analysis was used in conjunction with geochemical modeling to investigate the evolution of the chemical composition of groundwater. PHREEQC was used for inverse geochemical modeling. It is demonstrated that the groundwater, recharged mainly in the northern low mountains, acquired its mineralization properties principally from water–rock interactions, i.e., dissolution of evaporates and reverse cation exchange. The dissolution of halite, Glauber’s salt, dolomite and calcite determined the Na+, Cl−, Mg2+, Ca2+, SO4 2− and HCO3 − chemistry, but evaporation and precipitation also influenced the water composition. The shallow groundwater of Lop Nur was characterized by high salinity and slow circulation.

Mucosal (oral) immunization of mice with carrier-delivered ricin toxoid (RT) vaccine was accomplished by one long (7 weeks) or two short (4 weeks) immunization schedules. For the long and short immunization schedule two lots of vaccine were administered prepared with the same procedure but at different occasions. The long schedule consisted of a total of seven doses of 50 microg of vaccine in microencapsulated (lot #108) or aqueous form administered on days 1, 2, 3, 28, 29, 30 and 49. With the short schedule a total of seven or six doses of 25 microg (lot #111) were administered on days 1, 2, 3, 14, 15, 16 and 30, or on 1, 2, 14, 15, 30, 31 and 32, respectively. Mice immunized orally with the long schedule, 50 microg of RT vaccine incorporated into poly-DL-lactide-co-glycolyde (DL-PLG) microspheres (MS) produced serum IgG, IgG2a and IgA ELISA antibodies. All mice immunized with RT in DL-PLG MS (RT-MS) were protected against a lethal ricin aerosol challenge. In contrast, with the same schedule and with the same dose, the aqueous vaccine (RT) failed to stimulate IgG, IgG2a and IgA antibodies, and these mice were not protected against an aerosol ricin toxin challenge. With the shorter immunization scheme, seven doses of 25 microg RT-MS stimulated a significant, though reduced, protection with the microencapsulated, but not with the aqueous vaccine. When the first and second 3-day cycles of the short immunization schedule was reduced to two doses, and the 3-day cycle was administered at the end of the schedule, neither RT-MS nor RT stimulated protection against the challenge. These results indicated that successful oral immunization with RT-MS depended on both the dose and the schedule, consisting of three consecutive days of administration in two cycles, 4 weeks apart. Altering this schedule and the dose, resulted in a reduced protection or no protection at all. Furthermore, under the conditions of this study, the advantage of the microencapsulated RT vaccine over the aqueous vaccine for effective oral immunization was well demonstrated.

Intranasal (i.n.) immunization with ricin toxoid (RT) vaccine encapsulated in poly (lactide-co-glycolide) microspheres (RT-PLG-Ms) and poly (L-lactide) microspheres (RT-PLA-Ms) stimulated systemic and mucosal immune responses and protected mice from aerosolized ricin intoxication. High titers of anti-ricin IgG2a were stimulated in the serum of mice with one or two doses of RT-Ms 6 weeks postimmunization. However, in the lungs, no IgG2a or total IgG was elicited either with RT-Ms or with aqueous RT. At 6 weeks postimmunization, a single dose of the RT-Ms stimulated secretory IgA (sIgA) in the lungs of four of six mice, but a second immunizing dose did not enhance the stimulation. A single dose of aqueous RT vaccine failed to stimulate sIgA in the lungs, while, a second dose induced sIgA in 50% of the mice. One or two i.n. doses of RT-Ms protected most of the mice against lethal aerosol-delivered ricin toxin 6 weeks postimmunization. In contrast, protection was absent or marginal after one or two doses of aqueous RT vaccine. In both studies, the protection against lethal aerosol challenge was significantly better with one dose of RT-Ms than with two doses of aqueous vaccine, which may be attributed to the induction of sIgA in the lungs and the serum. Duration of the IgG2a and IgA in the serum, particularly that of IgG2a was much longer after the administration of RT-Ms than after the aqueous vaccine. The geometric mean IgG2a titers stimulated with two doses of RT-Ms remained high during 40 weeks postimmunization and were up to 25 times higher than the titers induced with aqueous RT vaccine. After 6 weeks, the IgG2a induced by two doses of aqueous vaccine was no longer detectable. Persistence of antibody response was predictive of efficacy. At 1 year postimmunization with two doses of RT-Ms, 100% of mice were protected against lethal ricin challenge. However, at the same time no protection was afforded by two doses of aqueous RT. The results of the present study consistently demonstrated the advantages of microencapsulated RT vaccine to stimulate effective and long-lasting protection by i.n. administration.

Poly (N-isopropylacrylamide) (PIPA) was grafted to polyallylamine hydrochloride (PA1Am • HCl) by amide formation under the influence of water soluble carbodiimide 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The graft polymer was made into microspheres (MS) by chemical cross-linking. The pH responsive drug release of the graft polymer microspheres was examined by releasing phenobarbital natrium (PN) which was carried on the microspheres by physical adsorption. A dynamic dialysis technique was used in the drug release experiment and the drug release rate constants reflecting the drug release characteristic of polymer microspheres were obtained by constituting a mathematical model. The results indicated that the homopolymer PA1Am microspheres and the copolymer PA1Am-g-PIPA microspheres are both pH responsive to release PN and in neutral pH condition the release rate is the slowest.

Poly(N-isopropylacrylamide) (PIPA) was synthesized by radical polymerization with 2,2′-azobisisobutyronitrile (AIBN) as an initiator and 3-mercaptopropionic acid (MPA) as a chain-transfer reagent in methanol (MeOH) at 70°C for 7 h. The resultant PIPA was grafted to polyallylamine hydrochloride (PAIAm · HCI) by amide formation under the influence of water-soluble carbodiimide 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The graft polymer was made into microspheres (MS) by chemical crosslinking. The pH-responsive drug release of the graft polymer microspheres was examined by releasing phenobarbital natrium (PN), which was carried on the microspheres by physical adsorption. A dynamic dialysis technique was used in the drug-release experiment and the drug-release-rate constants reflecting the drug release characteristic of polymer microspheres were obtained by constituting a mathematical model. The results indicated that the homopolymer PAIAm microspheres and the copolymer PAIAm-g-PIPA microspheres are both pH responsive to release PN and that in the neutral pH condition the release rate is the slowest. © 1995 John Wiley & Sons, Inc.

Biodegradable microparticles made of poly(lactide-co-glycolide) (PLG) were used for protracted and pulsed-release of the incorporated ricin toxoid (RT) vaccine to reduce the multiple immunization doses and the time required to induce complete protection against lethal aerosol-borne ricin challenge. The release rate of RT encapsulated in PLG microparticles was controlled by polymer selection and varying the preparation procedures, which allowed us to control microparticle size and the distribution of the vaccine in the polymeric matrix. PLG-microparticles in which RT vaccine was distributed heterogeneously in small pockets stimulated a rapid antibody response which was independent of the polymeric composition of the carriers. PLG-microparticles in which RT vaccine was distributed homogeneously throughout the polymeric matrix induced a slower antibody response, which depended on the polymeric composition of the carriers. Administration of RT in homogeneous microparticles made from 50/50 PLG or 100% polylactide stimulated two distinct anti-ricin IgG peaks, while RT in heterogeneous microparticles stimulated identical IgG peaks. An early (3 weeks) and long-lasting (1 year or longer) anti-ricin antibody response was evoked by a single administration of encapsulated RT vaccine when prepared by the above-mentioned conditions. In contrast, three administrations of the aqueous RT were required to stimulate similar antibody response. Reduction of immunization time from 6 to 4 weeks was achieved with RT encapsulated in small homogeneous microparticles but not with homogeneous large microparticles. These results demonstrated the usefulness of biodegradable microparticles to improve the efficacy of immunization with RT vaccine and probably many other vaccines as well.

Poly(lactide-co-glycolide) microparticles, containing ricin toxoid or fluorescein isothiocyanate-labeled bovine serum albumin were prepared by a water-in-oil-in-water emulsion solvent extraction procedure with a high encapsulation efficiency (from 60% to 94%). Three agitation methods: vortex mixing, homogenization and sonication, were used to make the first inner w/o emulsion and the second w/o/w emulsion. The effects of process parameters on structure, surface condition, particle size, core loading and in vitro release properties of the protein-loaded microparticles were studied. SDS-PAGE analysis showed that none of the agitation methods damaged the structural integrity and stability of the encapsulated protein. Confocal laser scanning microscopic analysis and in vitro studies indicated that heterogeneous microparticles provided a fast release profile with a large protein burst (62%), and homogeneous microparticles released protein slower with a much lower protein burst (7%). These properties may influence the dynamics of the antibody response.

Polyallylamine-graft-poly(N-isopropylacrylamide) was prepared by coupling polyallylamine with poly(N-isopropylacrylamide) (the latter with an end-standing carboxyl group). The graft polymer obtained showed a temperature-responsive phase transition under alkaline conditions, whereas the starting poly(N-isopropylacrylamide) with end-standing carboxyl group showed temperature-sensitivity under acidic conditions. With an increase in the degree of grafting the temperature-sensitivity of the polymer under weakly alkaline conditions increases. Microspheres were prepared by cross-linking the graft polymers with glutaraldehyde in water-in-oil emulsion. Trypsin immobilized to the microspheres showed temperature-responsiveness in its catalytic activity. The graft polymer can be used as a component of temperature-sensitive devices in various forms.

Reactive microspheres suitable for binding proteins were prepared using emulsifier-free emulsion copolymerizations of styrene (St) and acrolein (AL) with various molar ratios of monomers St and AL. A maximum polymerization rate was obtained when the molar ratio of the monomers was 1 : 1. The diameter of the latex particles increased with increase in the amount of monomer AL. The amounts of aldehyde groups on the latex particle surfaces were determined by conductometric titration. The binding capacity of the copolymer latexes with spacer molecules was also examined.