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WIREs Nanomed Nanobiotechnol
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Novel approaches for drug delivery systems in nanomedicine: effects of particle design and shape

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Abstract The identification of novel drug candidates for the treatment of diseases like cancer, infectious diseases, or allergies (especially asthma) assigns new tasks for pharmaceutical technology. With respect to drug delivery several problems occur such as low solubility and hence low bioavailability or restriction to inconvenient routes of administration. Nanotechnological approaches promise to circumvent some of these problems, therefore being well suited for future applications as nanomedicines. Furthermore, efficient and sufficient loading is a critical issue that is approached through mesoporous particles and/or through nonspherical particles both offering larger volumes and surfaces. Special interest is laid on the effect of shape of particulate materials on the body and related physiological mechanisms. The modified response of biological systems on different shapes opens a new dimension to adjust particle system interaction. Finally, the biological response to these systems will determine the fate with respect to their therapeutic value. Therefore, the interaction pattern between nonspherical particulate materials and biological systems as well as the production processes are highlighted. WIREs Nanomed Nanobiotechnol 2012, 4:52–65. doi: 10.1002/wnan.165 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Applications of functionalized nanoparticles and research aims in nanomedicine. The surface of nanoparticles can be modified with various molecules such as fluorescence dyes or biological ligands (e.g., antibodies). Furthermore, drug molecules can be encapsulated or adsorbed to nanoparticles. Adding parts or all of these functionalities turns the nanoparticle into a sensor, an imaging aid for diagnosis, or a directed carrier, respectively.

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Schematic representation of silica‐lipid hybrid (SLH) microcapsule formation and scanning electron micrograph of the microcapsules. Celecoxib‐containing SLH microcapsules were prepared via a two‐step process including the homogenization and the following spray‐drying of the silica‐stabilized emulsions. (Reprinted with permission from Ref 78. Copyright 2009)

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Colored SEM images of alveolar macrophages (brown) interacting with polystyrene (PS) particles (purple). (a) The cell body (brown) can be seen at the end of an elliptical disk and the membrane has progressed down the length of the particle. (b) A cell has attached to the flat side of an elliptical disk and has spread on the particle. (c) A spherical particle has attached to the top of a cell and the membrane has progressed over approximately half the particle. Scale bar: (a) 10 µm, (b) and (c) 5 µm. (Reprinted with permission from Ref 25. Copyright 2007 NCBI)

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Illustration of vessel with bifurcation. Certain nonspherical particles are reported to accumulate in close proximity to the walls and therefore can exit main vasculature more easily. This is depicted through the gradual transition of the lightness from the center towards the lateral regions. Lighter regions contain more nonspherical objects. The smaller vessel is supplied from the lateral region of the main vessel and consequently lighter.

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Membranes used for the formation of cylindrical and nonspherical particles formed via molds, or template‐assisted techniques. (a) SEM image of a cross section of an alumina membrane (internal diameter = 210 nm) with an extremely high aspect ratio (>1000) of uniform nanopores. (Reprinted with permission from Ref 38. Copyright 2006 ACS Publications) (b) SEM image showing the (top) surface of the alumina membrane with a perfect hexagonal arrangement of the nanopores. (Reprinted with permission from Ref 38. Copyright 2006 ACS Publications) (c) SEM image of a track‐etched polycarbonate membrane (PC) with a pore diameter of 1 µm. (Reprinted with permission from Ref 36. Copyright 1997 RSC Publishing) (d) Fluorescence micrograph of poly(lactic‐co‐glycolic acid) (PLGA) particles created through the hydrogel template approach representing some symbols of a computer keyboard. (Reprinted with permission from Ref 44. Copyright 2010 Springer) (e) SEM images of 3 µm arrow‐shaped poly(ethylene glycol) (PEG) particles fabricated by the particles replication in nonwetting templates (PRINT) technique. (Reprinted with permission from Ref 45. Copyright 2005 ACS Publications) (f) SEM image of a polymeric particle that was made in a microfluidic device polymerized by light. The inset shows the transparency mask feature that was used to make the corresponding particle. (Reprinted with permission from Ref 46. Copyright 2006 Nature Publishing Group) (g) SEM image of artificial red blood cells which were formed using the layer‐by‐layer (LbL) technique. Inset shows close up image. (Reprinted with permission from Ref 33. Copyright 2009 NCBI)

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Selection of nonspherical particles fabricated using different strategies: SEM images of nonspherical polystyrene (PS) particles created by a stretching technique in the form of (a) elliptical disks and (b) UFOs. (Reprinted with permission from Ref 25. Copyright 2006 NCBI) (c) Fluorescence microscopy shows an isolated filamentous block copolymer associate (filomicelle). (Reprinted with permission from Ref 4. Copyright 2007 Nature Publishing Group) (d) Schematic of the filomicelle structure: yellow/green indicates hydrophobic polymer, orange/blue is hydrophilic. (Reprinted with permission from Ref 4. Copyright 2007 Nature Publishing Group)

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Sketch of the possible approaches to increase the drug loading capacity of nanoparticles which is offered by porous and nonspherical particles in comparison to spherical particles. Different biological responses and subsequent application schemes are the consequence.

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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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