One of the key challenges in anticancer therapy is the toxicity and poor bioavailability of the anticancer drugs. Nanotechnology can play a pivotal role by delivering drugs in a targeted fashion to the malignant cells that will reduce the systemic toxicity of the anticancer drug. In this report, we show a stepwise development of a nanoparticle-based targeted delivery system for in vitro and in vivo therapeutic application in pancreatic cancer. In the first part of the study, we have shown the fabrication and characterization of the delivery system containing gold nanoparticle as a delivery vehicle, cetuximab as a targeting agent, and gemcitabine as an anticancer drug for in vitro application. Nanoconjugate was first characterized physico-chemically. In vitro targeting efficacy, tested against three pancreatic cancer cell lines (PANC-1, AsPC-1, and MIA Paca2) with variable epidermal growth factor receptor (EGFR) expression, showed that gold uptake correlated with EGFR expression. In the second part, we showed the in vivo therapeutic efficacy of the targeted delivery system. Administration of this targeted delivery system resulted in significant inhibition of pancreatic tumor cell proliferation in vitro and orthotopic pancreatic tumor growth in vivo. Tumor progression was monitored noninvasively by measuring bioluminescence of the implanted tumor cells. Pharmacokinetic experiments along with the quantitation of gold both in vitro and in vivo further confirmed that the inhibition of tumor growth was due to targeted delivery. This strategy could be used as a generalized approach for the treatment of a variety of cancers characterized by overexpression of EGFR.

Stereolithography using photo-cross-linkable polymeric biomaterials is an effective technique for fabricating highly complex three-dimensional (3D) scaffolds with controlled microstructures for tissue engineering applications. In this study, we have optimized the UV curable polymer solution composition and laser parameters for the stereolithography machine. Poly(propylene fumarate) (PPF) was used as the biomaterial, diethyl fumarate (DEF) was used as the solvent, and bisacrylphosphrine oxide (BAPO) was used as the photoinitiator. Three different weight ratios of PPF/DEF and BAPO contents were characterized by measuring the viscosities and thermal properties of the un-cross-linked solutions and the mechanical properties of the formed scaffolds. After optimizing the resin composition by satisfying both the viscosity limitation and the mechanical requirement, laser parameters such as critical exposure (Ec) and penetration depth (Dp) were determined from the working curve and the relationship between laser speed and energy by measuring the thickness of predesigned windows fabricated in stereolithography with different ranges of Ec and Dp. Three-dimensional scaffolds with various pore sizes, pore shapes, and porosities were designed in computer-aided design (CAD) software and were fabricated in stereolithography. The fabricated scaffolds were characterized by measuring external dimensions, porosities, mean pore sizes, and compressive moduli and were compared to the CAD models. Feature accuracy in the xy-plane was achieved and overcuring of the resin in z-axis was minimized. The stereolithographically fabricated scaffolds with controlled microstructures can be useful in diverse tissue engineering applications.

A theoretical and experimental investigation of relaxation dynamics is carried out for binary mixtures of entangled short and long chains of the same species. In disagreement with the previous theories of Doi et al. [Macromolecules 1987, 20, 1900] and Viovy et al. [Macromolecules 1992, 24, 3587], the new experimental data indicate that the terminal relaxation time associated with the long chains decreases systematically with the short chain length and with the weight fraction φ of the long chains for all the mixtures. These experimental observations have inspired the proposal of a new reptation theory to account for (1) the tube dilation (TD) due to the constraint release by short chains, (2) impedance of the long chain's curvilinear diffusion, and (3) enhanced contour length fluctuation, all resulting from the incorporation of the short chains of length N S. The various increases of the long chain's relaxation rate with lowering φ for its mixtures with different short chain lengths are possible only if the long chain reptates in a dilated tube of a shorter contour length with a curvilinear diffusivity that depends nontrivially on φ and N S. The short chain's influence on the long chain's curvilinear diffusion, characterized by an impedance function λ that explicitly depends on N S and φ, is demonstrated by comparison between the theory and experiment. Finally, the contour length fluctuation (CLF) is found to be enhanced in the binary mixtures and to produce additional concentration dependence for the terminal relaxation time; i.e., the CLF correction is larger at lower concentrations and for lower molecular weights of the long chains.

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