Browsing by Author "Pothayee, Nikorn"

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    Ammonium Bisphosphonate Polymeric Magnetic Nanocomplexes for Platinum Anticancer Drug Delivery and Imaging with Potential Hyperthermia and Temperature-Dependent Drug Release
    Zhang, Rui; Fellows, Benjamin; Pothayee, Nikorn; Hu, Nan; Pothayee, Nipon; Jo, Ami; Bohórquez, Ana C.; Rinaldi, Carlos; Mefford, Olin Thompson; Davis, Richey M.; Riffle, Judy S. (Hindawi, 2018-08-05)
    Novel magnetite-ammonium bisphosphonate graft ionic copolymer nanocomplexes (MGICs) have been developed for potential drug delivery, magnetic resonance imaging, and hyperthermia applications. The complexes displayed relatively uniform sizes with narrow size distributions upon self-assembly in aqueous media, and their sizes were stable under simulated physiological conditions for at least 7 days. The anticancer drugs, cisplatin and carboplatin, were loaded into the complexes, and sustained release of both drugs was observed. The transverse NMR relaxivities (s) of the complexes were 244 s−1 (mM Fe)−1 which is fast compared to either the commercial T2-weighted MRI agent Feridex IV® or our previously reported magnetite-block ionomer complexes. Phantom MRI images of the complexes demonstrated excellent negative contrast effects of such complexes. Thus, the bisphosphonate-bearing MGICs could be promising candidates for dual drug delivery and magnetic resonance imaging. Moreover, the bisphosphonate MGICs generate heat under an alternating magnetic field of 30 kA·m−1 at 206 kHz. The temperature of the MGIC dispersion in deionized water increased from 37 to 41°C after exposure to the magnetic field for 10 minutes, corresponding to a specific absorption rate of 77.0 W·g−1. This suggests their potential as hyperthermia treatment agents as well as the possibility of temperature-dependent drug release, making MGICs more versatile in potential drug delivery applications.
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    Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in vivo intracellular Salmonella model
    Ranjan, Ashish; Pothayee, Nikorn; Seleem, Mohamed N.; Tyler, Ronald D.; Brenseke, Bonnie; Sriranganathan, Nammalwar; Riffle, Judy S.; Kasimanickam, Ramanathan K. (Dove Medical Press, 2009-01-01)
    Pluronic based core-shell nanostructures encapsulating gentamicin were designed in this study. Block copolymers of (PAA(+/-)Na-b-(PEO-b-PPO-b-PEO)-b-PAA(+/-)Na) were blended with PAA(-) Na(+) and complexed with the polycationic antibiotic gentamicin to form nanostructures. Synthesized nanostructures had a hydrodynamic diameter of 210 nm, zeta potentials of -0.7 (+/-0.2), and incorporated approximately 20% by weight of gentamicin. Nanostructures upon co-incubation with J774A.1 macrophage cells showed no adverse toxicity in vitro. Nanostructures administered in vivo either at multiple dosage of 5 microg g(-1) or single dosage of 15 microg g(-1) in AJ-646 mice infected with Salmonella resulted in significant reduction of viable bacteria in the liver and spleen. Histopathological evaluation for concentration-dependent toxicity at a dosage of 15 microg g(-1) revealed mineralized deposits in 50% kidney tissues of free gentamicin-treated mice which in contrast was absent in nanostructure-treated mice. Thus, encapsulation of gentamicin in nanostructures may reduce toxicity and improve in vivo bacterial clearance.
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    Development of Core-Shell Polymeric Nanostructures for Delivery of Diagnostic and Chemotherapeutic Agents
    Pothayee, Nikorn (Virginia Tech, 2010-12-08)
    Macromolecular complexes of anionic-nonionic block copolymers and cationic antibiotic aminoglycosides have been formed by electrostatic condensation. Amphiphilicity of the complexes was introduced into the shells by incorporating a hydrophobic poly(propylene oxide) segment into the block copolymer. The resulting particles have an average hydrodynamic diameter of ~ 200 nm and contain up to 30-40 % of the drug payload. In vitro efficacies of such nanostructures in reduction of intracellular pathogens like Salmonella, Listeria, and Brucella were demonstrated. Current effort focuses on translation of this nano-drug delivery concept to in vivo model of intracellular infectious diseases. Atom transfer radical polymerization (ATRP) was utilized to prepare well-defined polymeric dispersion stabilizers that readily adsorb onto metal oxide surfaces. Two unimolecular bis(phosphonate) ATRP initiators were designed and prepared in good yield. These special initiators were successfully used to initiate polymerization of poly(N-isopropylacrylamide) (PNIPAM) in a controlled manner yielding PNIPAM with a bis(phosphonate) moiety at one terminus. The polymers readily adsorbed onto magnetite nanoparticle surfaces, thus creating thermosensitive magnetic nanostructures that form nanosized clusters upon heating above the lower critical solution temperature of PNIPAM. It is envisioned that modularity of this approach, relying on the applicability of ATRP to polymerize a vast array of monomers, could be used to prepare a library of polymeric shells for magnetic iron oxide nanoparticles. Medical intervention in drug delivery that includes detectability of drug carriers is greatly desirable. A real-time assessment of disease prognosis could be highly beneficial for developing personalized treatment strategies. As an example of this conceptual innovation, block ionomer functionalized magnetite complexes were synthesized and investigated as carriers for delivery of aminoglycosides into phagocytic cells for treatment of intracellular bacterial infections. The ionic block of copolymer contains multiple carboxylates for binding onto the iron oxide surface. The remaining unbound carboxylate anions were used to complex with cationic gentamicin in nanoshells of these complexes. The iron oxide particle core provides an imaging modality and serves as a pseudo-crosslinking site to enhance stabilities of the polyelectrolyte complexes, thus preventing them from disintegrating in the physiological environment. Currently, these hybrid complexes are being investigated in possible pharmaceutical formulations to eradicate intracellular pathogens in animal models.
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    Remote Actuation of Magnetic Nanoparticles For Cancer Cell Selective Treatment Through Cytoskeletal Disruption
    Master, Alyssa M.; Williams, Philise N.; Pothayee, Nikorn; Pothayee, Nipon; Zhang, Rui; Vishwasrao, Hemant M.; Golovin, Yuri I.; Riffle, Judy S.; Sokolsky, Marina; Kabanov, Alexander V. (Springer Nature, 2016-09-20)
    Motion of micron and sub-micron size magnetic particles in alternating magnetic fields can activate mechanosensitive cellular functions or physically destruct cancer cells. However, such effects are usually observed with relatively large magnetic particles (> 250 nm) that would be difficult if at all possible to deliver to remote sites in the body to treat disease. Here we show a completely new mechanism of selective toxicity of superparamagnetic nanoparticles (SMNP) of 7 to 8 nm in diameter to cancer cells. These particles are coated by block copolymers, which facilitates their entry into the cells and clustering in the lysosomes, where they are then magneto-mechanically actuated by remotely applied alternating current (AC) magnetic fields of very low frequency (50 Hz). Such fields and treatments are safe for surrounding tissues but produce cytoskeletal disruption and subsequent death of cancer cells while leaving healthy cells intact.