Method for Preparing Porous Shells or Gels from Glass Particles

A method is provided for preparing shells, concentric shells or porous, homogenous gels from alkali borate glass particles at low temperatures (i.e. room temperature or less than above 100° C.). The alkali borate glass particles contain one or more cations such as aluminum which react with an aqueous solution containing an anion such as hydroxide to form an aqueous insoluble material having a solubility limit of less than about 0.01 wt. percent. TTie resulting shells or gels may be used in many different applications such as a filler in resins, as filters, precursors for nano-sized powders, as thin surface films or catalyst support media. The resulting shells or gels may also have a chemotherapeutic drug added thereto, following which the resulting product is administered to a mammal and the insoluble material is dissolved form the product in vivo through administration of chelating agent

Glass microspheres for medical applications

Radioactive dysprosium lithium borate glass microspheres have been developed as biodegradable radiation delivery vehicles for the radiation synovectomy treatment of rheumatoid arthritis. Once injected into a diseased joint, the microspheres deliver a potent dose of radiation to the diseased tissue, while a non-uniform chemical reaction converts the glass into an amorphous, porous, hydrated dysprosium phosphate reaction product --Abstract, page iv

Preparation and Properties of Porous Microspheres Made from Borate Glass

Dysprosium lithium-borate glass microspheres and particles, ranging from 45 to 150 m in diameter, were reacted with a 0.25M phosphate solution at 37°C, whose pH was either 3 or 8.8. The glass reacted nonuniformly and was converted into a porous, amorphous, hydrated, dysprosium phosphate reaction product. The amorphous product had the same volume and shape (pseudomorphic) as the unreacted glass, and could be dried without cracking. After heating at 300°C for 1 h, the amorphous reaction product had a specific surface area of 200 m2/g, a pore size of 30 nm, and nominal crushing strength of 10 MPa. when the reaction product was heated to 600°C for 15 min, the specific surface area decreased to 90 m2/g and the nominal crushing strength increased to 35 MPa. Heating above 615°C converted the amorphous dysprosium phosphate product into crystalline DyPO4, which contained open porosity until heated above 800°C for 15 min. Highly porous materials of different chemical composition can be prepared by chemically reacting a borate-based glass with an aqueous solution at low-temperature (\u3c100°C). These highly porous materials are easy to process, and are considered candidates for controlled drug delivery, catalysis, chromatographic separation, filtration, and as bioactive materials

Glass Formation and Chemical Durability of Dysprosium Lithium Borate Glasses Intended for in Vivo Radiation Synovectomy

The glass formation and structure/property relationships for Dy2O3-Li2O-B2O3 glasses were investigated. Such glasses are currently being considered for in vivo radiation delivery vehicles. Chemical dissolution tests were conducted in simulated synovial fluid (pH 7.4, at 37°C, for 11 d) to evaluate the release of dysprosium from selected glasses. The chemical durability, Tg, nD and density increased as either the Li2O or Dy2O3 content in a glass was increased. Such property trends are attributed to increased crosslinking within the glass structure as BO3 triangles are converted to BO4 tetrahedra. A proposed structural model assumes dysprosium is incorporated into the glass with a coordination number of eight and is surrounded by four BO4 tetrahedra. Glasses containing ≥ 1.0 mol% Dy2O3 released less than 0.1% of their initial dysprosium content after being immersed in simulated synovial fluid for 11 d at 37°C. These glasses are considered safe for in vivo radiation delivery from the standpoint of radiation release, since dysprosium will be the only radioisotope in the glass during treatment

In Vitro and in Vivo Dissolution Behavior of a Dysprosium Lithium Borate Glass Designed for the Radiation Synovectomy Treatment of Rheumatoid Arthritis

Dysprosium lithium borate (DyLB) glass microspheres were investigated for use in the radiation synovectomy treatment of rheumatoid arthritis. In vitro testing focused on weight loss and cation dissolution from glass microspheres immersed in simulated synovial fluid (SSF) at 37°C for up to 64 days. In vivo testing was performed by injecting glass microspheres into the stifle joints of Sprague-Dawley rats and monitoring the biodegradability of the microspheres and the tissue response within the joints. The DyLB microspheres reacted nonuniformly in SSF with the majority of lithium and boron being dissolved, whereas nearly all of the dysprosium (\u3e99.7%) remained in the reacted microspheres. Because the DyLB glasses released negligible amounts of dysprosium while reacting with SSF, they are considered safe for radiation synovectomy from the standpoint of unwanted radiation release from the joint capsule. Furthermore, the DyLB microspheres fragmented, degraded, and reacted with body fluids while in the joints of rats without histologic evidence of joint damage

A Biodegradable Radiation Delivery System Utilizing Glass Microspheres & EDTA Chelation Therapy

Dysprosium lithium-borate (DyLB) glass microspheres have been developed as a biodegradable radiation delivery vehicle for the treatment of rheumatoid arthritis and other diseases. Radioactive microspheres of these glasses are intended to be injected into a joint infected with rheumatoid arthritis to safely deliver a localized dose (100 Gy) of beta radiation. Once injected, the microspheres react nonuniformly with body fluids. The nonradioactive, lithium-borate component is dissolved from the glass, whereas the radioactive 165Dy reacts with phosphate anions in the body fluids, and becomes chemically trapped in a solid, dysprosium phosphate reaction product that has the same size as the unreacted microsphere. The glass microspheres lose 80% of their weight after nonuniform reaction (\u3c1 day), but the dysprosium phosphate reaction product is slowly metabolized by the body over several months. Ethylenediaminetetraacetate (EDTA) chelation therapy can be used to dissolve the dysprosium phosphate reaction product in vitro in \u3c2 h. The dysprosium phosphate reaction product which formed in vivo in the joint of a Sprague-Dawley rat was also dissolved by EDTA chelation therapy in \u3c1 week, without causing any detectable joint damage. The combination of DyLB glass microspheres and EDTA chelation therapy provides a unique tool for the medical community because it can deliver a large dose (\u3e100 Gy) of localized beta radiation to a treatment site within the body, followed by complete biodegradability

⁶Li, ⁷Li Nuclear Magnetic Resonance Investigation of Lithium Coordination in Binary Phosphate Glasses

6Li and 7Li solid state magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy has been used to investigate the local coordination environment of lithium in a series of xLi2O·(1-x)P2O5 glasses, where 0.05≤x≤0.55. Both the 6Li and 7Li show chemical shift variations with changes in the Li2O concentration, but the observed 6Li NMR chemical shifts closely approximate the true isotropic chemical shift and can provide a measure of the lithium bonding environment. The 6Li NMR results indicate that, in this series of lithium phosphate glasses, the Li atoms have an average coordination between four and five. The results for the metaphosphate glass agree with the coordination number and range of chemical shifts observed for crystalline LiPO3. An increase in the 6Li NMR chemical shift with increasing Li2O content was observed for the entire concentration range investigated, correlating with increased cross-linking of the phosphate tetrahedral network by O-Li-O bridges. The repolymerization of the glass structure occurs with the sharing of edges, faces and vertices of Li-O polyhedra. The 6Li chemical shifts were also observed to vary monotonically through the anomalous glass transition temperature (Tg) minimum. This continuous chemical shift variation shows that abrupt changes in the Li coordination environment do not occur as the Li2O concentration is increased, and such abrupt changes can not be used to explain the Tg minimum

Hepatic Tumor Radioembolization in a Rat Model Using Radioactive Rhenium (¹⁸⁶Re/¹⁸⁸Re) Glass Microspheres

Purpose: the aim of this study was to fully characterize newly developed radioactive rhenium glass microspheres in vivo by determining their biodistribution, stability, antitumor effect, and toxicity after hepatic arterial injection in a syngeneic rat hepatoma model. The dose response of the tumors to increasing amounts of radioactive 186Re and 188Re microspheres was also determined. Methods and Materials: Rhenium glass microspheres were made radioactive by neutron activation and then injected into the hepatic artery of Sprague-Dawley rats containing 1-week-old Novikoff hepatomas. The biodistribution of the radioactivity and tumor growth were determined 1 h and 14 days after injection. Results: Examination of the biodistribution indicated a time-dependent, up to 7-fold increase in Novikoff hepatoma uptake as compared to healthy liver tissue uptake. After 14 days, the average T:L ratio was 1.97. Tumor growth in the rats receiving radioactive microspheres was significantly lower than in the group receiving nonradioactive microspheres (142% vs. 4824%, p = 0.048). Immediately after injection, 0.065% of the injected radioactivity was measured in the thyroid; it decreased to background levels within 24 h. Conclusion: Radioactive rhenium microspheres are effective in diminishing tumor growth without altering hepatic enzyme levels. The microspheres are safe with respect to their radiation dose to healthy tissue and radiation release in vivo and can be directly imaged in the body with a gamma camera. Furthermore, rhenium microspheres have an advantage over pure beta-emitting microspheres in terms of preparation and neutron-activation time. In sum, this novel radiopharmaceutical may provide an innovative and cost-effective approach for the treatment of nonresectable liver cancer

Investigation of Sodium Distribution in Phosphate Glasses Using Spin-echo ²³Na NMR

The spatial arrangements of sodium cations for a series of sodium phosphate glasses, xNa2O•(100-x)P2O5 (x ≤ 55), were investigated using 23Na spin-echo NMR spectroscopy. The spin-echo decay rate is a function of the Na-Na homonuclear dipolar coupling, and is related to the spatial proximity of neighboring Na nuclei. The spin-echo decay rate in these sodium phosphate glasses increases nonlinearly with higher sodium number density, and thus provides a measure of the Na-Na extended range order. The results of these 23Na NMR experiments are discussed within the context of several structural models, including a decimated crystal lattice model, cubic dilation lattice model, a hard sphere (HS) random distribution model, and a pairwise cluster hard sphere model. While the experimental 23Na spin-echo M2 are described adequately by both the decimated lattice and the random HS models, it is demonstrated that the slight nonlinear behavior of M2 as a function of sodium number density is more correctly described by the random distribution in the HS model. At low sodium number densities the experimental M2 is inconsistent with models incorporating Na-Na clustering. The ability to distinguish between Na-Na clusters and nonclustered distributions becomes more difficult at higher sodium concentrations