Synthesis and Characterization of Lipid-Polymer Hybrid Nanoparticles for Combinatorial Drug Delivery
University of Kansas
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Abstract Overcoming obstacles like multidrug resistance, short circulation half-life, and nonspecific systemic distribution is an ongoing challenge in cancer therapy. One application to address these concerns is to engineer a drug delivery vehicle that has versatile functionality, good serum stability, circulates in the body long enough to reach the targeting tissues, and is biocompatible. A promising formulation platform that embodies these features is the lipid-polymer hybrid nanoparticles. The surface characteristics of these nanoparticles such as charge, lipid density, and targeting ligands can be modified to allow for specific cellular uptake, controlled drug releases kinetics, and enhanced pharmacokinetics. In this work, it was found that the hybrid nanoparticles could easily be fabricated with negatively and positively charged lipids in order to change the overall surface charge. The particle size remained in the desirable range and the distribution was narrow. The lipid-polymer hybrid nanoparticle by design has the capacity to co-encapsulate hydrophobic and lipophilic drugs. To investigate, camptothecin and a cisplatin derivative were dually loaded within the hybrid nanoparticle system. This combination formulation was characterized by dynamic light scattering for particle size, zeta potential, and polydispersity index as well as in vitro drug release and cytotoxicity. The particle size was below 100 nm and the distribution was narrow. The release studies showed that the addition of the two drugs within the lipid-polymer hybrid nanoparticle system did not affect the release profiles of the individual drugs. The ability for co-encapsulation and the similar overall drug release profiles for camptothecin and cisplatin derivative in the combination compared to single drug loaded controls valuates this already useful drug delivery platform.
- Pharmaceutical Chemistry Dissertations and Theses 
- Theses 
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