title: Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications.
abstract: Dendrimers are discrete nanostructures/nanoparticles with 'onion skin-like' branched layers. Beginning with a core, these nanostructures grow in concentric layers to produce stepwise increases in size that are similar to the dimensions of many in vivo globular proteins. These branched tree-like concentric layers are referred to as 'generations'. The outer generation of each dendrimer presents a precise number of functional groups that may act as a monodispersed platform for engineering favourable nanoparticle-drug and nanoparticle-tissue interactions. These features have attracted significant attention in medicine as nanocarriers for traditional small drugs, proteins, DNA/RNA and in some instances as intrinsically active nanoscale drugs. Dendrimer-based drugs, as well as diagnostic and imaging agents, are emerging as promising candidates for many nanomedicine applications. First, we will provide a brief survey of recent nanomedicines that are either approved or in the clinical approval process. This will be followed by an introduction to a new 'nanoperiodic' concept which proposes nanoparticle structure control and the engineering of 'critical nanoscale design parameters' (CNDPs) as a strategy for optimizing pharmocokinetics, pharmocodynamics and site-specific targeting of disease. This paradigm has led to the emergence of CNDP-directed nanoperiodic property patterns relating nanoparticle behaviour to critical in vivo clinical translation issues such as cellular uptake, transport, elimination, biodistribution, accumulation and nanotoxicology. With a focus on dendrimers, these CNDP-directed nanoperiodic patterns are used as a strategy for designing and optimizing nanoparticles for a variety of drug delivery and imaging applications, including a recent dendrimer-based theranostic nanodevice for imaging and treating cancer. Several emerging preclinical dendrimer-based nanotherapy concepts related to inflammation, neuro-inflammatory disorders, oncology and infectious and ocular diseases are reviewed. Finally we will consider challenges and opportunities anticipated for future clinical translation, nanotoxicology and the commercialization of nanomedicine.
authors.affiliation: Department of Ophthalmology, Center for Nanomedicine, Baltimore, MD, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Kannan
authors.forename: E
authors.initials: E
authors.lastname: Nance
authors.forename: S
authors.initials: S
authors.lastname: Kannan
authors.forename: D A
authors.initials: DA
authors.lastname: Tomalia
mesh_terms: D002986:Clinical Trials as Topic; D050091:Dendrimers / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D017277:Drug Approval; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D050997:Nanomedicine / Q000379:methods*
chemical_list: D050091:Dendrimers
keywords: critical nanoscale design parameters; dendrimers; drug delivery; nanomedicine; nanoperiodic concept