Dual and multi-drug delivery nanoparticles towards neuronal survival and synaptic repair

Among the macromolecular drug targets in neurodegenerative disorders, the neurotrophin brain-derived neurotrophic factor（BDNF） and its high-affinity tropomyosin-related kinase receptor（Trk B） present strong interest for nanomedicine development aiming at neuronal and synaptic repair. Currently, BDNF is regarded as the neurotrophic factor of highest therapeutic significance. However, BDNF has delivery problems as a protein drug. The enhanced activation of the transcription factor CREB（c AMP response element-binding protein） has been evidenced to increase the BDNF gene expression and hence the production of endogenous BDNF. We assume that BDNF delivery by nanocarriers and mitochondrial protection may provide high potential for therapeutic amelioration of the neuroregenerative strategies. Beneficial therapeutic outcomes may be expected for synergistic dual or multi-drug action aiming at（i） neurotrophic protein regulation in the central and peripheral nervous systems, and（ii） diminishment of the production of reactive oxygen species（ROS） and the oxidative damage in mitochondria. Our research strategy is based on a nanoarchitectonics approach for the design of nanomedicine assemblies by hierarchical self-assembly. We explore nanoarchitectonics concepts in soft-matter nanotechnology towards preparation of biodegradable self-assembled lipid nanostructures for safe neuro-therapeutic applications of multi-target nanomedicines.

HPLC Quantification of Dexamethasone Palmitate in Bronchoalveolar Lavage Fluid of Rat after Lung Delivery with Large Porous Particles

A high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of dexamethasone palmitate (DXP) in bronchoalveolar fluid lavage samples (BALF). DXP in rat BALFs containing the internal standard (IS), testosterone decanoate (TD), was extracted using a mixture of chloroform and methanol (9:1, v/v). Extracts were then centrifuged, dried and dissolved in acetonitrile. A chromatographic separation based on an isocratic elution was done using acetonitrile and water (85:15, v/v) as a mobile phase at a flow rate of 1.2 mL/min. The graph of the developed method was linear within the tested calibration range of 0.5 - 40 μg/mL. The overall extraction recovery of DXP from BALF samples was 84.3% ± 1.6%. The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. This methodology has been applied to determine levels of DXP in BALF samples collected from rats treated with DXP large porous particles. The measured concentrations were successfully evaluated using a non-compartment pharmacokinetic model. Since the developed method requires only a microvolume (100 μL) of BALF sample for analysis, it is therefore particularly suitable for the evaluation of drug biodistribution in lung.

Cancer drug resistance: rationale for drug delivery systems and targeted inhibition of HSP90 family proteins

Nanocarriers have been developed in order to protect drugs or to improve drugs efficiency by reaching the damaged tissue and avoiding systemic and local toxicity.By using HSP90 inhibitors,some cancer drug resistances have been overcome and the loading into nanocarriers of such drugs has shown an increase of their activities.This review will present some advantages of HSP90 inhibitors to treat resistant tumors;especially those targeting the mitochondrial protein TRAP1.We will also focus on the targeting of the primary tumors,cancer stem cells and metastatic cells.