It is also conceivable that other chemical functionalizations, such as covalent modification with ammonium or methotrexate, may also enable internalization of CNT, non-specifically in multiple cell types [98]. == In recent years, the drug delivery field has experienced an exponential growth Rabbit Polyclonal to 4E-BP1 of interest in the role played by the carriers geometry (i.e., shape and size) in its functions drug loading and release, stability, toxicity and, ultimately, delivery performance. Intuitively, one coulda prioripostulate that this geometry governs the carriers behaviorin vivo: circulation and elimination, permeation into, retention in and clearance from tissues, interaction with target cells and subcellular trafficking and final addressing of a cargo. Biology provides numerous examples of the key role of geometry in transporting features of large spherical leukocytes, small spherical lipoproteins, large discoid erythrocytes, small discoid platelets, and rod-like and filamentous microbes of diverse size. Alas, the limitations of the previous methods to vary and control the geometry of drug delivery systems (DDS) did not favor systematic experimental efforts in this area of research. Most DDS designed in the last three decades have either spherical (e.g., 10-DEBC HCl liposomes, dendrimers and micelles) or irregular morphology (protein conjugates, linear backbone polymer conjugates, polyplexes). However, the development of methods for formulation and characterization of polymeric drug carriers enabled design of carriers with versatile and defined geometries. This article represents an attempt to systematically analyze the rapidly growing body of experimental data obtainedin vitroand in animal studies using carriers of diverse morphologies 10-DEBC HCl and geometries. == 2. Types of drug delivery carrier geometries == There is an immense body of literature on spherical carriers, varying in size from a few nanometers (quantum dots, small micelles and dendrimers) to 50 500 nanometers (liposomes, polymer 10-DEBC HCl carriers, large dendrimers, lipoproteins) to microns (blood cells and polymer carriers). Any attempt to review these carriers would be unrealistic; in this paper they will be discussed mainly as a comparison group with non-spherical carriers of corresponding size. nonspherical carriers discussed in this paper include anisotropic polymer particles such as flat nanodisks, molded nanocubes or cylinders, elongated liposomes, filamentous polymer micelles (filomicelles, also referred to as worm micelles), filamentous polymer nanocarriers and carbon nanotubes. Schematics of these geometries are depicted inFigure 1. == Physique 1. DDS geometries. == Schematics of the different geometry carriers are shown in order of 10-DEBC HCl increasing aspect ratio. It should be noted that PRINT particles are crosslinked PEG nanogels, as opposed to the other PEGylated drug delivery systems (DDS) where one end of the PEG is usually free. Blue indicates PEGylation. Red indicates hydrophobic polymer. Thick black lines on liposomes represent polar groups 10-DEBC HCl of phospholipids, while yellow indicates non-polar tails. A blown-up fluorescence microscopy image of PEO PCL filomicelle is usually shown, where the carrier was stained with the lipophilic dye PKH26. Scale bar is usually 10 m. Filomicelles were formed with standard film casting/dehydration and subsequent rehydration with polymer purchased from Polymer Source Inc., Dorval (Montreal), Quebec, Canada. The common chemical structure is usually shown in the blown-up image of CNT. Structure is usually 5,5-armchair conformation for a non-spiraled SWNT. From the standpoint of size, many of these carriers, traditionally called nanocarriers, exceed the National Science Foundation (NSF) dimensional limits defined for nanoscale (< 100 nm), yet fit within broader nanoscale definitions (< 1,000 nm). Furthermore, the termnanostructure refers to any non-spherical carrier with at least one dimension that is less than one micron, typically less than 100 nm. The unique physical, chemical and optical properties of nanostructures hold promise for a variety of applications in drug delivery. By virtue of their small size, nanoscale materials offer distinctive advantages including unique pharmacokinetics (see sections 4 and 5, below). From a geometric argument,nanocarriers have an enormous surface area to volume.