Polymeric Nanocarriers for Transport Modulation across the Pulmonary Epithelium: Dendrimers,Polymeric Nanoparticles,and their Nanoblends

The purpose of this study was to (a) Determine the cellular transport and uptake of amine-terminated generation 3 (G3) poly(amido amine) (PAMAM) dendrimers across an in vitro model of the pulmonary epithelium, and the ability to modulate their transport by forming nanoblends of the dendrimers with biodegradable solid polymeric nanoparticles (NPs) and (b) to formulate dendrimer nanocarriers in portable oral inhalation devices and evaluate their aerosol characteristics. To that end, fluorescein isothiocyanate (FITC)-labeled G3 PAMAM dendrimer nanocarriers (DNCs) were synthesized, and also encapsulated within poly lactide-co-glycolide nanoparticles (NPs). Transport and uptake of both DNCs encapsulated within NPs (nanoblends) and unencapsulated DNCs were tracked across polarized monolayers of airway epithelial cells, Calu-3. DNCs were also formulated as core-shell microparticles in pressurized metered-dose inhalers (pMDIs) and their aerodynamic properties evaluated by Andersen cascade impaction. The apparent permeability of DNCs across the airway epithelial model was similar to that of a paracellular marker of comparable molar mass—order of 10⁻⁷ cm s⁻¹. The transport and cellular internalization of the DNCs can be modulated by formulating them as nanoblends. The transport of the DNCs across the lung epithelium was completely suppressed within the time of the experiment (5 h) when formulated as blends. The encapsulation also prevents saturation of the cellular internalization profile. Nanoblending may be a potential strategy to modulate the rate of transport and cellular uptake of DNCs, and thus be used as a design strategy to achieve enhanced local or systemic drug delivery.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9588-5) contains supplementary material, which is available to authorized users.KEY WORDS: Calu-3, dendrimers, nanoparticles, nanoblends, oral inhalation, pressurized metered-dose inhalers, transport modulation     

Thermally stable La2LiSbO6:Mn4+,Mg2+ far-red emitting phosphors with over 90% internal quantum efficiency for plant growth LEDs

In this paper, we reported on the high-efficiency and thermally-stable La₂LiSbO₆:Mn⁴⁺,Mg²⁺ (LLS:Mn⁴⁺,Mg²⁺) far-red emitting phosphors. Under 338 nm excitation, the composition-optimized LLS:0.3%Mn⁴⁺,1.6%Mg²⁺ phosphors which were made up of [SbO₆], [LiO₆], and [LaO₈] polyhedrons, showed intense far-red emissions peaking at 712 nm (²E_g → ⁴A_2g transition) with internal quantum efficiency as high as 92%. The LLS:0.3%Mn⁴⁺,1.6%Mg²⁺ phosphors also exhibited high thermal stability, and the emission intensity at 423 K only reduced by 42% compared with its initial value at 303 K. The far-red light-emitting device has also been made by using the LLS:0.3%Mn⁴⁺,1.6%Mg²⁺ phosphors and a 365 nm emitting InGaN chip, which can emit far-red light that is visible to the naked eye. Importantly, the emission spectrum of the LLS:0.3%Mn⁴⁺,1.6%Mg²⁺ phosphors can match well with the absorption spectrum of phytochrome P_FR, indicating the potential of these phosphors to be used in plant growth light-emitting diodes.

Double perovskite La₂LiSbO₆:Mn⁴⁺,Mg²⁺ far-red emitting phosphors with internal quantum efficiency as high as 92% and good thermal stability were developed for plant growth LEDs.     

Preparation,characterization, and luminescence properties of double perovskite SrLaMgSbO6:Mn4+ far-red emitting phosphors for indoor plant growth lighting

Mn⁴⁺-activated SrLaMgSbO₆ far-red emitting phosphors with double perovskite structure were prepared by traditional solid-state reaction. The research on the crystal structure of the SrLaMgSbO₆:0.8%Mn⁴⁺ (SLMS:0.8%Mn⁴⁺) phosphors showed that the as-prepared sample was made up of two polyhedrons, [SbO₆] and [MgO₆]. Under the excitation of 333 nm, the SLMS:0.8%Mn⁴⁺ phosphors exhibited an intense far-red emission in the 625–800 nm wavelength range with CIE chromaticity coordinates of (0.733, 0.268), which could match well with the absorption spectrum of phytochrome P_FR. The optimal concentration of Mn⁴⁺ ions in the SLMS:Mn⁴⁺ phosphors was 0.8 mol%. Importantly, the as-prepared SLMS:0.8%Mn⁴⁺ phosphors had an internal quantum efficiency of 35%. The thermal stability of SLMS:0.8%Mn⁴⁺ phosphors was also investigated, and the activation energy was found to be 0.3 eV. Thus, the Mn⁴⁺-activated SLMS phosphors have great potential to serve as far-red emitting phosphors in indoor plant growth lighting.

Novel far-red emitting double perovskite SrLaMgSbO₆:Mn⁴⁺ phosphors were prepared and their photoluminescence properties were studied for applications in indoor plant growth lighting.     

Health benefits of resveratrol: Evidence from clinical studies

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5′-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH–associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.     

Postoperative Cardiac Arrhythmias in Children

Opinion statement