• Development and Evaluation of Nano-herbal Therapy for Metastatic Breast Cancer Treatment

      Wong, Ho-Lun; Fassihi, Reza; Blass, Benjamin E.; Dürig, Thomas (Temple University. Libraries, 2018)
      Triptolide (TPL), a diterpenoid triepoxide that is extracted from a traditional Chinese herb called Tripterygium Wilfordii (also known as ‘Thunder God Vine’) has recently drawn increasing interests from pharmaceutical and biomedical researchers, especially in the aspect of its potential efficacy on multiple cancer treatment. TPL has shown significant growth and proliferation inhibition activities in a broad range of cancer cell types. Moreover, it has shown the inhibition of osteoclastogenesis by breast cancer bone metastasis. However, due to its limitation in toxicity, solubility and non-specific biodistribution, it is challenging for the application of TPL in clinical study. Besides, TPL can rapidly distribute in most vital organs and no evidences shown tissue accumulation of drug. It is indispensable to overcome those barriers and optimize the properties and performance of the promising drug molecule. Lipid-based nanocarriers such as nanostructured lipid carriers (NLC) have been extensively studied for delivery of poorly-water soluble drug compounds. They also have the potential to optimize the physicochemical properties of the drug and may enhance a targeted delivery of the drug to specific therapeutic site. Alendronate (Fosamax®), an FDA approved bisphosphonate drug for osteoporosis, osteogenesis imperfecta and several other bone diseases, has been used as a bone targeting decoration agent. Breast cancer cell line MDA-MB-231 and other type of cancer cell lines have been used to study the in vitro cytotoxicity of TPL and the carriers while MC3T3-E1 cell line was used for toxicity assessment. Rats have also been used to study the in vivo performance of the drug. After modifying and optimizing the formulation of the particle, the formulation had the ability to remain structurally and functionally stable when being in the bio-simulated media at 37 °C and in water at room temperature with high encapsulation efficiency. In vitro study illustrated that both TPL free drug (stock solution 10mg/mL dissolved in DMSO) and TPL nanoparticle without alendronate (TPL-NP) had similar cytotoxicity on MDA-MB-231 and some other type of cancer cell lines. The ALE decoration on the particle (ALE-NP-TPL) has enhanced the anti-cancer effect especially with breast cancer cell line. The in vivo study shows that after 24 hours of the dose injection at local bone site, the formulation and TPL can remained at the location without random distribution to other organs. TPL-NP has not only successfully optimized the physicochemical properties of the drug, but also shows great enhancement of therapeutic effect both in vitro and in vivo study.
    • Evaluation of Small Unilamellar Vesicles as a Removal Method of Benzo[a]pyrene from Humic Substances in Soils

      Kim, Bojeong; Grandstaff, David E.; Chemtob, Steven M. (Temple University. Libraries, 2019)
      Polycyclic aromatic hydrocarbons (PAHs) are highly hydrophobic and lipophilic and are readily retained by soil surfaces and organic matter. Hence, several techniques have been developed in an effort to economically and effectively remove them from soil solids. Their strong affinity to soil organic matter limits their biodegradation processes by microorganisms, making them persistent in the soil environment. Recently, the use of “small unilamellar vesicles” (SUVs), nano-scale lipid aggregates, has been proposed as a means to enhance these microbial degradations, by effectively solubilizing lipophilic PAHs from the soil solids. In this thesis, laboratory-scale batch experiments were performed to examine this potential by measuring the uptake of benzo[a]pyrene (BaP), a model PAH compound, by SUVs from a simulated soil organic matter. This environmental surface was created by coating silica (SiO2) nanospheres with a layer of poly-L-lysine, followed by humic acid, and characterized by dynamic light scattering for particle size and zeta potential values. Then, these humic acid-bound SiO2 particles were saturated with BaP and then equilibrated with SUVs. The uptake of BaP by SUVs was measured through fluorescence spectroscopy, and the average amount of BaP concentrated in the 1 mg/L humic acid-bound SiO2 particles was found to be 1.77 µg/L. After one week of equilibration with SUVs, 94.4% and 83.6% of the added BaP was solubilized by SUVs (in solutions containing 50 mg/L and 100 mg/L of vesicles, respectively), indicating an excellent ability to extract BaP from the soil organic particles. SUVs can therefore be an effective vehicle to enhance the biodegradability of PAHs in soils, with potential as an environmentally sustainable and affordable method.