Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes
Cátia Ornelas-Megiatto1, Parth N Shah, Peter R Wich
1College of Chemistry, University of California, Berkeley, California 94720-1460, United States.
Molecular Pharmaceutics
|October 3, 2012
Summary
Degradable acetalated dextran (Ac-DEX) nanoparticles effectively encapsulate a silver carbene complex (SCC) for enhanced antibacterial activity. These nanoparticles show promise for pulmonary drug delivery due to improved aerosolization and sustained release.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Pharmaceutical Sciences
Background:
- Silver carbene complexes (SCC) possess potent antimicrobial properties but face challenges in delivery.
- Degradable polymers offer potential for controlled drug release and targeted delivery systems.
- Developing effective nanoparticle formulations is crucial for enhancing the efficacy of hydrophobic drugs.
Purpose of the Study:
- To formulate and characterize degradable acetalated dextran (Ac-DEX) nanoparticles loaded with a hydrophobic silver carbene complex (SCC).
- To evaluate the antibacterial efficacy and drug release profile of SCC-loaded Ac-DEX nanoparticles.
- To assess the suitability of these nanoparticles for pulmonary drug delivery.
Main Methods:
- Nanoparticle formulation using a single-emulsion process with varying Ac-DEX and aqueous phase ratios.
- Characterization of nanoparticle morphology, size distribution (SEM, TEM, DLS), and SCC loading/encapsulation efficiency.
- In vitro antibacterial testing against Gram-negative and Gram-positive bacteria.
- Assessment of aerosolization properties for pulmonary delivery.
Main Results:
- Optimal nanoparticle formulation achieved with a 1:5 volume ratio of Ac-DEX in dichloromethane to PBS, yielding particles of 100 ± 40 nm.
- SCC loading increased with feed concentration up to 30% (w/w), with peak encapsulation efficiency at 20% (w/w).
- SCC-loaded Ac-DEX nanoparticles demonstrated broad-spectrum activity against tested bacteria, inhibiting growth effectively.
- Nanoparticles exhibited sustained drug release compared to free SCC and superior suspension and aerosolization properties for pulmonary delivery.
Conclusions:
- Degradable Ac-DEX nanoparticles are a viable carrier for hydrophobic SCC, enhancing its antibacterial efficacy.
- The optimized formulation provides controlled release and improved characteristics for pulmonary administration.
- Ac-DEX nanoparticles represent a promising platform for developing advanced antimicrobial therapies via inhalation.
Related Concept Videos
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
01:27Chemical Agents for Microbial Control
Chemicals play important roles in controlling microbial growth by targeting microbial structures and functions as sanitizers, antiseptics, disinfectants, and sterilants.Alcohols are commonly used sanitizers, effectively disrupting lipid membranes, which compromises cell integrity. They are also used as antiseptics and disinfectants due to their rapid action and versatility.Phenols and their derivatives phenolics , known for denaturing proteins and disrupting cell membranes, are particularly...
01:09Colloidal precipitates
The high insolubility of some precipitates can result in an unfavorable relative supersaturation. This can lead to colloidal particles with a large surface-to-mass ratio, where adsorption is promoted. For instance, in the precipitation of silver chloride, silver ions are adsorbed on the surface of the colloidal particles, forming a primary layer. This layer attracts ions of opposite charge (such as nitrate ions), forming a diffuse secondary layer of adsorbed ions. This electric double layer...
01:15Antifungal Agents
Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...