Bound Volume Number

X

Document Type

Honors Capstone Project

Date of Submission

Spring 5-5-2015

Capstone Advisor

Prof. Rebecca Bader

Honors Reader

Prof. Christopher Nomura

Capstone Major

Biomedical and Chemical Engineering

Capstone College

Engineering and Computer Science

Audio/Visual Component

no

Capstone Prize Winner

no

Won Capstone Funding

yes

Honors Categories

Sciences and Engineering

Subject Categories

Therapeutics

Abstract

Polyhydroxyalkanoates (PHAs), a class of biopolyesters produced and stored by bacteria, have garnered attention for a number of industrial and biomedical applications. The goal of the current study was to extend the use of PHAs to drug delivery for the treatment of cancer. As a first step, the cytotoxicity of poly(3- hydroxy-octanoate-co-10-undecanoate) (PHOU) towards the A549 lung carcinoma cell line was determined and nanoparticles were prepared via a single emulsion technique. Elution tests, whereby cells were grown in fluid extracts obtained from media incubated for 24 hours at 37°C with PHOU films, did not result in any significant changes in cellular appearance or proliferation, as determined by microscopy and a WST-8 cellular proliferation assay. In contrast, direct contact assays that required growth of the cells on the PHOU films, resulted in cell death after 24 hours, as indicated by Live-Dead cell staining. PHOU nanoparticles with a size of a ~202 nm and a zeta potential of ~2.7 mV, as established using a Zetasizer Nano, were successfully prepared by nanoprecipitation. Ultimately, consistent nanoparticle development through single emulsion using PHOU was unsuccessful so a miniemulsion technique was used for following nanoparticle development. After achieving consistent nanoparticle development through double emulsion, folate groups were to be attached to the nanoparticles to specifically target cancer cells, but due to polymer cross-linking occurring through that attachment process that prevented successful folate attachment, nanoparticle development with new PHA polymers was necessary. PHO-N3 was successfully used to develop nanoparticles through mini-emulsion, a shorter and more efficient process than previous development methods. Through the use of a Zetasizer Nano, the size and zeta potential for the PHO-N3 nanoparticles were established as ~108 nm and -80 mV; suitable values for drug delivery. Although further assessment is required to establish the cytoxicity of the nanoparticles, the results provide preliminary evidence that nanoparticles of an appropriate size for drug delivery can be prepared.

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