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Polymeric nanoparticles made from natural and synthetic polymers have received the majority of attention due to their stability and ease of surface modification (Herrero-Vanrell et al., 2005; Vauthier et al., 2003). They can be tailor-made to achieve both controlled drug release and disease-specific localization by tuning the polymer characteristics and surface chemistry (Kreuter, 1994b; Moghimi et al., 2001; Panyam and Labhasetwar, 2003; Panyam et al., 2003b). It has been established that nanocarriers can become concentrated preferentially to tumors, inflammatory sites, and at antigen sampling sites by virtue of the enhanced permeability and retention (EPR) effect of the vasculature. Once accumulated at the target site, hydrophobic biodegradable polymeric nanoparticles can act as a local drug depot depending on the make-up of the carrier, providing a source for a continuous supply of encapsulated therapeutic compound(s) at the disease site, e.g., solid tumors.
These systems in general can be used to provide targeted (cellular or tissue) delivery of drugs, improve bioavailability, sustain release of drugs or solubilize drugs for systemic delivery. This process can be adapted to protect therapeutic agents against enzymatic degradation (i.e., nucleases and proteases) (Haixiong Ge, 2002). Thus, the advantages of using nanoparticles for drug delivery are a result of two main basic properties: small size and use of biodegradable materials. Nanoparticles, because of their small size, can extravasate through the endothelium in inflammatory sites, epithelium (e.g., intestinal tract and liver), tumors, or penetrate microcapillaries. In general, the nanosize of these particles allows for efficient uptake by a variety of cell types and selective drug accumulation at target sites (Desai et al., 1997; Panyam and Labhasetwar, 2003; Panyam et al., 2003b). Many studies have demonstrated that nanoparticles have a number of advantages over microparticles (>1 μm) as a drug delivery system (Linhardt, 1989). Nanoparticles have another advantage over larger microparticles because they are better suited for intravenous delivery. The smallest capillaries in the body are 5–6 μm in diameter. The size of particles being distributed into the bloodstream must be significantly smaller than 5 μm, without forming aggregates, to ensure that the particles do not cause an embolism.
The use of biodegradable materials for nanoparticle preparation allows for sustained drug release within the target site over a period of days or even weeks. Biodegradable nanoparticles formulated from PLGA and PLA have been developed for sustained drug delivery and are especially effective for drugs with an intracellular target (Barrera et al., 1993; Davda and Labhasetwar, 2002; Panyam and Labhasetwar, 2003). Rapid escape of hydrophobic PCL-coated nanoparticles from endo-lysosomes to the cytoplasm has been demonstrated (Barrera et al., 1993; Woodward et al., 1985). Greater and sustained anti-proliferative activity was observed in vascular smooth muscle cells that were treated with dexamethasone-loaded nanoparticles and then compared to cells given drug in solution (Redhead et al., 2001). Hence, nanoparticles can be effective in delivering their contents to intracellular targets.
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