Utility of biodegradable plasmonic nanoclusters in photoacoustic imaging.

Plasmonic metal nanoparticles are used in photoacoustic imaging as contrast agents because of their resonant optical absorption properties in the visible and near-IR regions. However, the nanoparticles could accumulate and result in long-term toxicity in vivo, because they are generally not biodegradable. Recently, biodegradable plasmonic gold nanoclusters, consisting of sub-5 nm primary gold nanoparticles and biodegradable polymer stabilizer, were introduced.

Controlled assembly of biodegradable plasmonic nanoclusters for near-infrared imaging and therapeutic applications.

Metal nanoparticles with surface plasmon resonance (SPR) in the near-infrared region (NIR) are of great interest for imaging and therapy. Presently, gold nanoparticles with NIR absorbance are typically larger than 50 nm, above the threshold size of approximately 5 nm required for efficient renal clearance. As these nanoparticles are not biodegradable, concerns about long-term toxicity have restricted their translation into the clinic.

Kinetic assembly of near-IR-active gold nanoclusters using weakly adsorbing polymers to control the size.

Clusters of metal nanoparticles with an overall size of less than 100 nm and high metal loadings for strong optical functionality are of interest in various fields including microelectronics, sensors, optoelectronics, and biomedical imaging and therapeutics. Herein we assemble approximately 5 nm gold particles into clusters with controlled size, as small as 30 nm and up to 100 nm, that contain only small amounts of polymeric stabilizers. The assembly is kinetically controlled with weakly adsorbing polymers, PLA(2K)-b-PEG(10K)-b-PLA(2K) or PEG (MW = 3350), by manipulating electrostatic, van der Waals (VDW), steric, and depletion forces.

Templated open flocs of anisotropic particles for pulmonary delivery with pressurized metered dose inhalers.

The challenges in forming stable drug suspensions in hydrofluoroalkane (HFA) propellants have limited drug dosages and efficiency of drug delivery with pressurized metered dose inhalers (pMDI). Herein, stable suspensions of weakly flocculated particles, in the shape of thin plates or needles, of a poorly water-soluble drug, itraconazole (Itz), are efficiently delivered by pMDI at high doses, up to 2.4 mg/actuation.

Small multifunctional nanoclusters (nanoroses) for targeted cellular imaging and therapy.

The ability of 20-50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report approximately 30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of gold-coated iron oxide nanoparticles.

Templated open flocs of nanorods for enhanced pulmonary delivery with pressurized metered dose inhalers.

Purpose: A novel concept is presented for the formation of stable suspensions composed of low density flocs of high aspect ratio drug particles in hydrofluoroalkane (HFA) propellants, and for subdividing (templating) the flocs with aerosolized HFA droplets to achieve high fine particle fractions with a pressurized metered dose inhaler.

Methods: Bovine serum albumin (BSA) nanorods, produced by thin film freezing (TFF), were added to HFA to form a suspension. Particle properties were analyzed with an Anderson cascade impactor (ACI), static and dynamic light scattering and optical microscopy.

Amorphous cyclosporin nanodispersions for enhanced pulmonary deposition and dissolution.

Aqueous colloidal dispersions of amorphous cyclosporin A (CsA) nanoparticles, intended for pulmonary delivery, were formed by antisolvent precipitation and stabilized with 10% polysorbate 80. Dissolution of the dispersion of CsA nanoparticles produced supersaturation values 18 times the aqueous equilibrium solubility. Nebulization of the dispersion to mice produced therapeutic lung levels and systemic concentrations below toxic limits.