Intraperitoneal delivery of paclitaxel by poly(ether-anhydride) microspheres effectively suppresses tumor growth in a murine metastatic ovarian cancer model

Intraperitoneal (IP) chemotherapy is more effective than systemic chemotherapy for treating advanced ovarian cancer, but is typically associated with severe complications due to high dose, frequent administration schedule, and use of non-biocompatible excipients/delivery vehicles. Here, we developed paclitaxel (PTX)-loaded microspheres composed of di-block copolymers of poly(ethylene glycol) and poly(sebacic acid) (PEG-PSA) for safe and sustained IP chemotherapy. PEG-PSA microspheres provided efficient loading (∼13 % w/w) and prolonged release (∼13 days) of PTX. In a murine ovarian cancer model, a single dose of IP PTX/PEG-PSA particles effectively suppressed tumor growth for more than 40 days and extended the median survival time to 75 days compared to treatments with Taxol® (47 days) or IP placebo particles (34 days). IP PTX/PEG-PSA was well tolerated with only minimal to mild inflammation. Our findings support PTX/PEG-PSA microspheres as a promising drug delivery platform for IP therapy of ovarian cancer and potentially other metastatic peritoneal cancers

Hydrogen migration in monoclinic zirconium dioxide and the effects of defects and dopants assessed by first-principles calculations

Thesis: S.M., Massachusetts Institute of Technology, Department of Nuclear Science and Engineering, 2016.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 80-82).Zirconium-based alloys, which have been employed as cladding materials in nuclear industry, pick up hydrogen during service because of corrosion in water. This is one of the degradation processes that challenge the safe operation of nuclear reactors. Composition of commercial zirconium-based alloys has been developed experimentally, aiming to improve corrosion and hydrogen resistance. The empirical testing process is costly, time-consuming and can provide little knowledge on the underlying mechanisms. In order to understand the critical step of hydrogen entering zirconium-based alloys, we study hydrogen migration in monoclinic zirconium dioxide (m-ZrO2 ), the oxide phase, which is present in the outer protective oxide layer contacting the cooling water. First principles calculations are casted to study hydrogen migration at atom-istic scale. All possible stable sites for hydrogen to take in the structure are determined based on energy minimization. Barriers and saddle point configurations of elemental diffusion paths are obtained using the nudged elastic band method. Each extended diffusion path can be constructed from these elemental migration steps ...by Ming Yang.S.M