Graduate Researcher, Virginia Tech
Using polymer nanoparticles as a delivery mechanism can be more effective and efficient than when administering the drug alone using traditional methods. By fluorescently tagging them, we can track the particles to ensure they are reaching their intended target. However, more is not necessarily better, there is an optimum fluorescent molecule loading because these molecules can quench each other and result in less signal. The surface of the particles can also be functionalized by adding targeting ligands to target specific biological markers and increase the specificity of delivery. My work is a systematic study looking at how changing parameters such as fluorophore loading or polymer compositions affects the characteristics on the resulting nanoparticles. Because every application requires slightly different traits, understanding how to tailor and manipulate the particle characteristics is essential to increase nanoparticle versatility and utility in the drug delivery field.
Abstract: Nanomaterials have been demonstrated as useful tools for molecular imaging, molecular diagnosis and targeted therapy in biomedical research. The main advantages of such nanomaterials are improved circulation times, precise targeting, enhancement of dissolution rates and enhanced contrast. A challenge and opportunity for nanotechnological strategies is that multiple functionalities, such as therapeutics, targeting, imaging and stimuli responsiveness can be achieved within one nanoparticle. Multifunctional nanoparticles are now actively under investigation and are imminent as the next generation of nanoparticles for providing custom and tailored treatment. This review considers contemporary approaches and possible future directions in the emerging area of multifunctional nanoparticles with a special focus on targeted drug delivery.
Pub.: 01 May '09, Pinned: 02 Aug '17
Abstract: Non-invasive medical imaging techniques such as positron emission tomography (PET) imaging are powerful platforms to track the fate of radiolabeled materials for diagnostic or drug delivery applications. Polymer-based nanocarriers tagged with non-standard PET radionuclides with relatively long half-lives (e.g. (64)Cu: t1/2 = 12.7 h, (76)Br: t1/2 = 16.2h, (89)Zr: t1/2 = 3.3 d, (124)I: t1/2 = 4.2 d) may greatly expand applications of nanomedicines in molecular imaging and therapy. However, radiolabeling strategies that ensure stable in vivo association of the radiolabel with the nanocarrier remain a significant challenge. In this study, we covalently attach radioiodine to the core of pre-fabricated nanocarriers. First, we encapsulated polyvinyl phenol within a poly(ethylene glycol) coating using Flash NanoPrecipitation (FNP) to produce stable 75 nm and 120 nm nanocarriers. Following FNP, we radiolabeled the encapsulated polyvinyl phenol with (125)I via electrophilic aromatic substitution in high radiochemical yields (> 90%). Biodistribution studies reveal low radioactivity in the thyroid, indicating minimal leaching of the radiolabel in vivo. Further, PEGylated [(125)I]PVPh nanocarriers exhibited relatively long circulation half-lives (t1/2 α = 2.9 h, t1/2 β = 34.9 h) and gradual reticuloendothelial clearance, with 31% of injected dose in blood retained at 24 h post-injection.
Pub.: 14 Apr '16, Pinned: 02 Aug '17
Abstract: Nanoparticle based drug delivery platforms have the potential to transform disease treatment paradigms and therapeutic strategies, especially in the context of pulmonary medicine. Once administered, nanoparticles disperse throughout the lung and many are phagocytosed by macrophages. However, there is a paucity of knowledge regarding cellular up-take dynamics of nanoparticles due largely to macrophage heterogeneity. To address this issue, we sought to better define nanoparticle up-take using polarized M1 and M2 macrophages and novel TIPS-pentacene loaded PEO-PDLLA nanoparticles. Our data reveals that primary macrophages polarized to either M1 or M2 phenotypes have similar levels of nanoparticle phagocytosis. Similarly, M1 and M2 polarized macrophages isolated from the lungs of mice following either acute (Th1) or allergic (Th2) airway inflammation also demonstrated equivalent levels of nanoparticle up-take. Together, these studies provide critical benchmark information pertaining to cellular up-take dynamics and biodistribution of nanoparticles in the context of clinically relevant inflammatory microenvironments.
Pub.: 04 Jan '17, Pinned: 02 Aug '17
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