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doi: 10.1007/s11095-010-0141-7pmid: 20593303
Central nervous system (CNS) diseases represent the largest and fastest-growing area of unmet medical need. Nanotechnology plays a unique instrumental role in the revolutionary development of brain-specific drug delivery, imaging, and diagnosis. With the aid of nanoparticles of high specificity and multifunctionality, such as dendrimers and quantum dots, therapeutics, imaging agents, and diagnostic molecules can be delivered to the brain across the blood-brain barrier (BBB), enabling considerable progress in the understanding, diagnosis, and treatment of CNS diseases. Nanoparticles used in the CNS for drug delivery, imaging, and diagnosis are reviewed, as well as their administration routes, toxicity, and routes to cross the BBB. Future directions and major challenges are outlined.
Tang, Cuyue; Prueksaritanont, Thomayant
doi: 10.1007/s11095-010-0157-zpmid: 20428930
Animal models are used commonly in various stages of drug discovery and development to aid in the prospective assessment of drug-drug interaction (DDI) potential and the understanding of the underlying mechanism for DDI of a drug candidate. In vivo assessments in an appropriate animal model can be very valuable, when used in combination with in vitro systems, to help verify in vivo relevance of the in vitro animal-based results, and thus substantiate the extrapolation of in vitro human data to clinical outcomes. From a pharmacokinetic standpoint, a key consideration for rational selection of an animal model is based on broad similarities to humans in important physiological and biochemical parameters governing drug absorption, distribution, metabolism or excretion (ADME) processes in question for both the perpetrator and victim drugs. Equally critical are specific in vitro and/or in vivo experiments to demonstrate those similarities, usually both qualitative and quantitative, in the ADME properties/processes under investigation. In this review, theoretical basis and specific examples are presented to illustrate the utility of the animal models in assessing the potential and understanding the mechanisms of DDIs.
doi: 10.1007/s11095-010-0156-0pmid: 20424893
Incorporating high binding affinity modifications, such as LNA and 2′F bases, increases AMO potency while maintaining specificity; nevertheless, use of low dose is preferred when using high potency reagents to minimize the potential for cross reactivity. 2′OMe/LNA chimeras with PS modifications were the most potent constructs tested for miRNA inhibition in vitro .
doi: 10.1007/s11095-010-0165-zpmid: 20454837
The ECG platform appears to offer an effective method of delivering nano-aerosols through the extrathoracic region, with minimal deposition, to the tracheobronchial airways and beyond. Aerosol deposition is then facilitated as enhanced condensational growth increases particle size. Future studies will investigate the effects of physio-chemical drug properties and realistic inhalation profiles on ECG growth characteristics.
Beers, Miranda; Sauerborn, Melody; Gilli, Francesca; Brinks, Vera; Schellekens, Huub; Jiskoot, Wim
doi: 10.1007/s11095-010-0172-0pmid: 20499141
The immunogenicity of the products in transgenic mice, unlike in wild-type mice, varied. In the transgenic mice, neither NABs nor immunological memory developed. The immunogenicity of rhIFNβ in a model reflecting the human immune system depends on the presence and the characteristics of aggregates.
doi: 10.1007/s11095-010-0181-zpmid: 20568001
The results suggest that the symmetric configuration findings in the previous studies can be used to explain the effects of CPEs under the asymmetric condition likely encountered in practice and to understand drug delivery enhancement in transdermal enhancer formulation development.
Bal, Suzanne; Ding, Zhi; Kersten, Gideon; Jiskoot, Wim; Bouwstra, Joke
doi: 10.1007/s11095-010-0182-ypmid: 20559701
In conclusion, TMC has an adjuvant function in transcutaneous immunisation with microneedles, but only if applied in a solution.
Ibsen, Stuart; Zahavy, Eran; Wrasdilo, Wolf; Berns, Michael; Chan, Michael; Esener, Sadik
doi: 10.1007/s11095-010-0183-xpmid: 20596761
The development of the DOX-PCB prodrug demonstrates the possibility of using light as a method of prodrug activation in deep internal tissues without relying on inherent physical or biochemical differences between the tumor and healthy tissue for use as the trigger.
Wang, Yiguang; Yang, Tingyuan; Wang, Xun; Wang, Jiancheng; Zhang, Xuan; Zhang, Qiang
doi: 10.1007/s11095-010-0184-9pmid: 20559700
These results suggested that RGD conjugated PEG-PLA micelles loading CA4 have potential as a new formulation for targeting angiogenic tumor vasculature.
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