Non-fluorine precursor solutions for high critical current density REBa₂Cu₃O₇₋x̳ films

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.In title on t.p., double underscored "x" appears as subscript.Includes bibliographical references (p. 68-71).The past two decades have seen advancements in high temperature superconducting cables for use in applications such as electrical transmission lines, propulsion systems, and mobile power generation systems. This work describes the development of a non-fluorine precursor solution for YBCO films with high critical current densities (Jc). An aqueous nitrate precursor solution system was selected from three possible precursor solution systems. It was further developed to produce YBCO films with Jc > 1 MA/cm2. Films up to ~800 nm thickness were made, and Jc > 1 MA/cm2 was obtained for films of over ~400 nm thickness. The developed aqueous solution contained a rheology modifier (hydroxyethyl cellulose / HEC), nitrates of Y, Ba, and Cu, and chelating agents (polyethylene glycol / PEG and sucrose). The total organic content was ~12 wt% of the entire solution, and the total cation concentration was ~0.7 M. The rheology modifying polymer determined the thickness of the deposited films. This allowed for the deposition of films with higher thickness than would be dictated by the total dissolved cations alone. A low temperature decomposition process was developed based on analyses of the chemical reactions that take place in the precursor films as they were heated. This process produced smooth and defect-free intermediate films that were stable under ambient conditions. These films were then heat treated to convert them into YBCO films. Recommendations for future work include further improvements to the precursor solution, including more effective chelating agents and possible alternative solvent systems. Intermediate films thicker than 2.5 [mu]m still tended to have surface defects.(cont.) Additional in-depth thermal analysis would further show how these defects develop, and adjustments to the decomposition process could be made accordingly. High resolution plan-view and cross-sectional microstructures of the films between the precursor state and their converted forms is recommended. These future studies will be valuable in further improving the performance and thickness of films derived from the non-fluorine precursor solution developed in this thesis.Yoda Rante Patta.S.M

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.National Institutes of Health (U.S.) (Grant R01 EB006365-06)Brain Science Foundation (Private Grant 106708

Local exposure and efficacy of a reservoir-based drug delivery device

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 2012.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 105-112).Prognoses for primary or metastatic brain tumor patients have been poor, despite developments in treatment over the last twenty years. 14,000 people die each year from glioblastoma multiforme (GBM). 200,000 new cases of breast cancer are diagnosed each year, with 15% of those patients experiencing multiple metastases into the brain. The primary cause of mortality is tumor recurrence, often centimeters away from the original lesion site. Current treatments involve systemic radiotherapy or chemotherapy, and improve median survival time by only a few months. Efforts to develop local treatment modules are motivated by the fact that patients experience systemic toxicities during conventional treatment. Implantable Gliadel® BCNU wafers were approved by the FDA, but patients still experienced side effects such as edema, and median survival time was improved only by 2 months. Convection-enhanced delivery (the infusion of chemotherapeutics via catheters) may achieve further distribution on the scale of centimeters, but there is a tendency for preferential flow along paths of least resistance. An implantable, biocompatible microcapsule for localized delivery of chemotherapeutics in the brain was developed in the Cima Lab. In vitro experiments confirmed linear initial rates of release of temozolomide, an alkylating agent, and doxorubicin, a topoisomerase inhibitor, from the microcapsules. In vivo survival studies were conducted to compare the efficacies of these microcapsules against 9L rat gliosarcoma and CRL1666 rat mammary adenocarcinoma tumors. Local delivery of temozolomide via implanted microcapsules was efficacious against both tumor types and comparable to or better than systemic delivery of temozolomide via oral gavage. Local delivery of doxorubicin was not efficacious against either tumor type, and not significantly distinguishable from control groups. Exposure data revealed much higher levels of retained temozolomide across a larger area of brain tissue than doxorubicin after microcapsule delivery. Thus, successful local delivery of chemotherapeutics in the brain depends on the achievement of sufficient exposures over sufficient (cm-length) distances away from the implant. Microcapsules developed for this work could potentially be implanted at different locations in the brain, with each achieving mm-distance exposure. The overlapping exposures would add together to help treat excess tumor cells post-resection and prevent tumor recurrence.by Yoda Rante Patta.Ph. D

Correction for Upadhyay et al., Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Correction for “Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain,” by Urvashi M. Upadhyay, Betty Tyler, Yoda Patta, Robert Wicks, Kevin Spencer, Alexander Scott, Byron Masi, Lee Hwang, Rachel Grossman, Michael Cima, Henry Brem, and Robert Langer, which appeared in issue 45, November 11, 2014, of Proc Natl Acad Sci USA (111:16071–16076; first published October 27, 2014, 10.1073/pnas.1313420110)