Browsing by Subject "Polymersomes"

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    Degradable Polymersomes for Targeted Drug Delivery
    (2013-08) Petersen, Matthew
    Chemotherapy today is often accompanied by major side effects due to delivery of toxic drugs to healthy tissue in addition to diseased cells. Targeted drug delivery offers the possibility of minimizing these side effects by specific delivery to cancer cells using targeted nanocarriers that enhance drug accumulation in tumors and facilitate target-specific cellular uptake. Polymersomes, vesicles self-assembled from polymeric amphiphiles, are an attractive targeted vehicle, as they are capable of encapsulating both hydrophobic and hydrophilic drugs, have lengthy circulation times in vivo, and can employ degradable functionality for triggered release of payload and clearance from the body. This thesis reports on efforts to enhance the capabilities of degradable polymersomes for targeted delivery. First, targeting functionality is incorporated into polymersomes of the block copolymer poly(ethylene oxide)-b-poly(γ-methyl-ε-caprolactone) by incorporating the reactive vinyl sulfone group into the amphiphile's hydrophilic terminus, allowing site-selective reaction with cysteine-functionalized targeting peptides following self-assembly. The performance of targeted delivery using this polymersome is then evaluated in vitro. Binding and delivery to model cell lines for targeted and bystander cells is tracked using nontargeted polymersomes and compared to that for polymersomes using a high- or low-affinity ligand. Polymer degradation is also tracked both in simple media and during cellular delivery. Finally, a new monomer is developed incorporating acid-labile acetal functionality into a cyclic polyester. The polymerization of this monomer to two distinct polymers is also characterized and the degradation behavior of both polymers evaluated.
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    Targeted delivery of polymer vesicles functionalized with fibronectin mimetic peptides to cancer cells
    (2012-09) Pangburn, Todd Owen
    Polymersomes, polymeric vesicles that self-assemble in aqueous solutions from block copolymers, have been avidly investigated in recent years as potential drug delivery agents. In this work, the feasibility of chemical conjugation of fibronectin mimetic targeting peptides (GRGDSP and PR_b) onto the surface of polymersomes is investigated, and the efficacy of these peptide functionalized polymersomes to achieve targeted delivery to cancer cells is studied. The diblock copolymer poly(ethylene oxide)-b-poly(1,2-butadiene) was synthesized and self-assembled to form polymersomes, which were subsequently functionalized with peptides using a ―click‖ conjugation reaction. Delivery efficacy of these peptide functionalized polymersomes loaded with fluorescent iii Abstract Polymersomes, polymeric vesicles that self-assemble in aqueous solutions from block copolymers, have been avidly investigated in recent years as potential drug delivery agents. In this work, the feasibility of chemical conjugation of fibronectin mimetic targeting peptides (GRGDSP and PR_b) onto the surface of polymersomes is investigated, and the efficacy of these peptide functionalized polymersomes to achieve targeted delivery to cancer cells is studied. The diblock copolymer poly(ethylene oxide)-b-poly(1,2-butadiene) was synthesized and self-assembled to form polymersomes, which were subsequently functionalized with peptides using a ―click‖ conjugation reaction. Delivery efficacy of these peptide functionalized polymersomes loaded with fluorescent markers, a chemotherapeutic (doxorubicin), or siRNA was assessed and compared. Both the efficacy and the process of delivery and internalization of peptide functionalized polymersomes were investigated for colon and breast cancer cells. PR_b functionalized polymersomes were found in all cases to significantly outperform both GRGDSP and non-functionalized polymersomes, in terms of promoting cell binding, internalization, specificity, and effective delivery. This work highlights peptide functionalized polymersomes in general, and PR_b functionalized polymersomes in specific, as a highly promising targeted delivery system.