Controlled nanoparticle release from a hydrogel by DNA-mediated particle disaggregation.

For many pharmaceutical applications, it is important that different drugs are present in the human body at distinct time points. Typically, this is achieved by a sequential administration of different therapeutic agents. A much easier alternative would be to develop a drug delivery system containing a whole set of medically active compounds which are liberated in an orchestrated and controlled manner. Yet, such a controlled, sequential release of drugs from a carrier system that can be used in a physiological situation is difficult to achieve. Here, we combine two molecular mechanisms, i.e. a build-up of osmotic pressure by the depletion of a control molecule and triggered disaggregation of nanoparticle clusters by synthetic DNA sequences. With this approach, we gain spatio-temporal control over the release of molecules and nanoparticles from a gel environment. The strategy presented here has strong implications for developing complex drug delivery systems for wound healing applications or for the sustained release of pharmaceuticals from a drug-loaded gel and will lower the need for multiple drug administrations.

Lipid emulsion pretreatment has different effects on mepivacaine and bupivacaine cardiac toxicity in an isolated rat heart model.

BACKGROUND: The use of lipid emulsions to reduce cardiac toxicity of local anaesthetics (LAs) has shown success in experimental studies and some clinical cases, and thus has been implemented in clinical practice. However, lipid treatment is usually given after the occurrence of neurological or cardiovascular symptoms of systemic intoxication. The aim of this study was to determine if pretreatment with lipid emulsion reduces cardiac toxicity produced by bupivacaine or mepivacaine. METHODS: Isolated rat hearts were perfused with or without lipid emulsion (0.25 ml kg(-1) min(-1)) before administration of equipotent doses of bupivacaine (250 µM) or mepivacaine (1000 µM). Haemodynamic parameters and times from start of perfusion LA to a 1 min period of asystole and recovery were determined. RESULTS: Pretreatment with lipid emulsion extended the time until occurrence of asystole and decreased times to recovery in bupivacaine-induced cardiac toxicity but not in mepivacaine-induced cardiac toxicity compared with control. Lipid pretreatment impaired rate-pressure product recovery in mepivacaine-intoxicated hearts. CONCLUSIONS: This study confirms that pretreatment with a lipid emulsion reduces cardiac toxicity of LAs. The efficacy of pretreatment with lipid emulsion was LA-dependent, so pharmacokinetic properties, such as lipophilicity, might influence the effects of lipid emulsion pretreatment.