Aerosolized Antimicrobial Agents Based on Degradable Dextran Nanoparticles Loaded with Silver Carbene Complexes

Abstract

Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH2Cl2 (organic): PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery.

Synthesis, characterization, in vitro SAR and in vivo evaluation of N,N′bisnaphthylmethyl 2-alkyl substituted imidazolium salts against NSCLC

“…Compounds 1–5 had chemical shifts in the range from 5.62 ppm to 5.81 ppm for this methylene linker, which was consistent with related compounds. 10,19,20 The 13 C NMR spectra for compounds 1–5 were consistent with the proposed structures.…”

Anti-tumor activity of lipophilic imidazolium salts on select NSCLC cell lines

“…One strategy that has been investigated to overcome both the issues of toxicity and resistance is the use of silver carbene complexes (SCCs) as chemotherapeutic agents. Silver, specifically the bioactive silver cation, has a long history as an efficacious antimicrobial agent, and N -heterocyclic carbenes have shown to be effective, relatively nontoxic ligands with which to deliver the silver cations (Garrison and Youngs, 2005; Garrison et al ., 2001a, b; Kascatan-Nebioglu et al ., 2006; Hindi et al ., 2008; Ornelas-Megiatto et al ., 2012). Furthermore, bacterial resistance to silver has been infrequent, allowing the medicinal use of silver since the 1800s (Russel et al ., 1994; Landsdown, 2002, 2004; Lansdown and Williams, 2004).…”

Use of Optical Fiber Sensor for Monitoring the Degradation of Ac-Dex Biopolymeric Nanoparticles

“…Its precursor, the water-soluble dextran, is a bacterially derived homopolysaccharide of glucose, FDA-approved, and widely available [3,4]. In turn, Ac-Dex is a hydrophobic material prepared by masking the hydroxyl groups of dextran with acetal groups and is easily processable by different emulsion techniques [2,5]. Ac-Dex nanoparticles (NPs) present the ability to encapsulate both hydrophobic and hydrophilic molecules, depending only on the emulsion process employed during their synthesis.…”

“…Ac-Dex nanoparticles (NPs) present the ability to encapsulate both hydrophobic and hydrophilic molecules, depending only on the emulsion process employed during their synthesis. Particles prepared by oil-in-water (o/w) or water-in-oil-in-water (w/o/w) emulsions are able to encapsulate either hydrophobic or hydrophilic molecules, respectively [5].…”