Control of Vancomycin Activity through the Encapsulation and Controlled Release from a Propargyl Acrylate-Poloxamer Nanocomposite System.

Vancomycin is a potent antibacterial drug that suffers from poor bioavailability due to its poor water solubility and relatively high molecular weight. Consequently, the application of vancomycin to treat bacteria-induced disease is limited. In this study, the ability of a temperature-stimulated propargyl acrylate-poloxamer nanocomposite (PAPN) system to encapsulate and release vancomycin is investigated. A controllable encapsulation and release system can be used to not only increase and prolong the bioavailability of vancomycin but also activate vancomycin with a temperature change. The PAPN system was prepared using an emulsion polymerization of propargyl acrylate followed by a surface decoration with a poloxamer at a precisely controlled grafting density. The activity of the PAPN system loaded with vancomycin is compared to that of the free drug and unmodified propargyl acrylate nanoparticles. It is shown that the activity of the PAPN system loaded with vancomycin is comparable to that of a freshly prepared, free-floating vancomycin solution. Upon storage, the activity of the free vancomycin in solution decreases, while the PAPN system loaded with vancomycin retains its high activity. Additionally, the PAPN system is able to effectively encapsulate and deactivate vancomycin until heated above a lower critical solution temperature (LCST). At temperatures above the LCST, the PAPN system releases vancomycin restoring the activity of the drug.

Temperature responsive nanoparticles: poloxamers as a modulator of Förster resonance energy transfer (FRET).

An effective strategy to control the Förster resonance energy transfer (FRET) of a donor/acceptor emitter pair that were attached to a 60 nm poly(propargyl acrylate)(PA) nanoparticle using temperature variations was developed. The size dependent properties of a poly-(ethylene oxide)-poly-(propylene oxide)-poly-(ethylene oxide) (PEO-PPO-PEO) block copolymer (poloxamer) was exploited to vary the spatial separation of the emitters and vary the FRET efficiency. Specifically, a 2% change in FRET efficiency between the donor/acceptor pair was achieved per 1 °C change in temperature from 49 °C to 60 °C when using a poloxamer of 2950 g mol-1 molecular weight, with sections of PPO consisting of 32 repeat units, PEO sections consisting of 12 repeat units and a lower critical solution temperature (LCST) of 58 °C. The methodology presented in this effort is easily extended to other temperature regimes through a judicious choice in poloxamer and corresponding LCST.