Browsing by Subject "Biopolymer"

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    BIO-BASED PLASTIC PACKAGING: A TOOL TO HELP ORGANIZATIONS ANALYZE THE TRADE-OFFS BETWEEN BIO-BASED AND CONVENTIONAL PLASTICS
    (2007-09-18T19:55:21Z) Bellucci, Nina
    An increasing number of companies are exploring ways to improve their environmental footprint. Some environmental benefits are offered by bio-based plastic packaging; however, this approach requires trade-offs. For example, plastic bottles made with polylactic acid (PLA), a bio-based plastic resin, lack the impact strength offered by plastic bottles made with polyethylene terephthalate (PET). Other trade-offs include diminished shelf life capabilities, increased cost, and recycling infrastructure. In particular, displacement of recyclable plastic packaging with plastics made from renewable resources has created controversy among environmental advocates. Despite its performance, cost, and recycling shortcomings, PLA offers an attractive choice to some because it represents the transition towards use of renewable resources. In an attempt to address trade-offs, I developed an analytical framework with assistance from key stakeholders. After identifying the fundamental objective of the best choice of resin for the manufacture of plastic bottles, I surveyed stakeholders to create a list of essential packaging criteria, with the three major criteria being performance as a bottle material, cost, and environmental impact. I relied on private interviews with industry experts and conference presentations to gather bottle data for four resins: PLA, PET, high density polyethylene (HDPE) and polypropylene (PP). The framework for comparison was Multiattribute Utility Theory (MAUT), a methodology designed to address trade-offs among multiple objectives to achieve an overall objective. Based on the survey results and best available data as input for MAUT, PET was the best choice of resin for the beverage bottle. This non-bio-based plastic emerged as the top choice largely due to its superior performance on criteria such as strength and shelf life. Further analysis of the characteristics of the four plastics showed that even if all environmental and cost characteristics of the bio-based plastic, PLA, were as favorable as any of the other plastics I analyzed, PLA still would not come to the top. Only if PLA’s performance as a bottle material (strength, etc.) increased several fold would PLA become the top choice among the four I analyzed. Similarly, analysis of the weighting of the criteria showed that increasing the weights on environmental criteria, compared to performance and cost criteria, cannot elevate PLA to the top choice, mainly because HDPE has desirable environmental characteristics such as recyclability. Only increasing the weight on environmental criteria such as greenhouse gas emissions while decreasing the weight on all other environmental criteria would allow PLA to become the top choice among the four bottle materials I analyzed.
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    Thermally-Responsive Biopolymer Depots for the Delivery of High-Dose, β-Radionuclide Brachytherapy in the Treatment of Prostate and Pancreatic Cancer
    (2018) Schaal, Jeffrey Laurence

    Intratumoral radiation therapy – ‘brachytherapy’ – is a highly effective treatment for solid tumors, particularly prostate cancer. Current titanium seed implants, however, are permanent and are limited in clinical application to indolent malignancies of low- to intermediate-risk. Attempts to develop polymeric alternatives, however, have been plagued by poor retention and off-target toxicity due to degradation.

    Herein, we report on a new approach whereby thermally sensitive micelles composed of an elastin-like polypeptide (ELP) are labeled with the radionuclide 131-Iodine to form an in situ hydrogel that is stabilized by two independent mechanisms: first, body heat triggers the radioactive ELP micelles to rapidly phase transition into an insoluble, viscous coacervate in under 2 minutes; second, the high energy β-emissions of 131-Iodine further stabilize the depot by introducing crosslinks within the ELP depot over 24 hours. These injectable brachytherapy hydrogels were used to treat two aggressive orthotopic tumor models in athymic nude mice: a human PC-3M-luc-C6 prostate tumor and a human BxPc3-luc2 pancreatic tumor model. The ELP depots retained greater than 52% and 70% of their radioactivity through 60 days in the prostate and pancreatic tumors with no appreciable radioactive accumulation (≤ 0.1% ID) in off-target tissues after 72 hours. The 131I-ELP depots achieved >95% tumor regression in the prostate tumors (n=8); with a median survival of more than 60 days compared to 12 days for control mice. For the pancreatic tumors, ELP brachytherapy (n=6) induced significant growth inhibition (p = 0.001, ANOVA) and enhanced median survival to 27 days over controls.

    We then demonstrated that 131I-ELP brachytherapy can work synergistically with paclitaxel chemotherapy to overcome the intrinsic resistance found in pancreatic tumors. Treating tumors with an optimized radioactivity dose of 10.0 µCi/mg and systemically administered paclitaxel nanoparticles achieved complete regression in BxPc3-luc2, MIA PaCa-2, and AsPc-1 tumor models. Moreover, responses occurred irrespective of the paclitaxel dose (between 12.5-50 mg/kg) or the formulation (Abraxane or micelle formulation). A comparative study utilizing an aggressive 5x 5Gy hypofractionated X-ray radiation produced only minor growth inhibition, with or without paclitaxel.

    The mechanistic underpinnings of this effect were explored in an orthotopic model to reveal the fundamental differences between 131I-ELP therapy and conventional radiotherapy. Continuous dose exposure was found to coordinate much more effectively with the temporal sensitization mechanisms of paclitaxel, as evidenced by TUNEL immunohistochemistry. Stromal collagen and cellular junctional proteins regulating interstitial permeability (Claudin-4, CD31, and VE-Cadherin) were dysregulated after 131I-ELP treatment. Fluorescent analysis of paclitaxel nanoparticles revealed significantly higher paclitaxel accumulation in brachytherapy tumors after treatment (p<0.01). These results show that 131I-ELP biopolymer brachytherapy offers a highly attractive alternative to current radiotherapy techniques and demonstrated negligible toxicity.