Nanoparticle coating with PEG offers therapeutic opportunities that were until recently unrealistic because of the efficient MPS uptake. This type of nanoparticle has significant advantages over uncoated ones, such as decreased MPS uptake, increased blood residence times, and dose-independent pharmacokinetics. A good agreement was found between theoretical thresholds to minimize protein adsorption [27, 30] and experimental thresholds to avoid plasma protein interaction [64], complement consumption [56], and interaction with phagocytic cells [43, 64].

The literature reviewed here showed the possibility of entrapping a variety of compounds in PEG-coated nano-particles, such as lipophilic drugs, proteins, and oligonu-cleotides, as well as genetic material. The release was controlled, and it was possible to preserve the biological activity of the entrapped material in PEG-coated nano-particles to a larger extent than in uncoated nanoparticles.

Given these advantages, The interest of these types of carriers for a variety of therapeutic applications was emphasized. Stealth nanospheres were suggested to be used as circulating depots to continuously deliver drugs to the blood compartment. These carriers could be of interest to deliver drugs to vascular lesions or in pathologies with leaky vascu-lature such as solid tumors or inflammatory and infectious sites, or to target spleen or lymph nodes. Moreover, it was shown that PEG-coated nanospheres could overcome the nasal [103] and the intestinal [104] barriers, and, therefore, this type of nanoparticles could be administered by nonin-vasive routes.

It also was demonstrated that PEG-coated nanoparticles could overcome the BBB, which represents an insurmountable obstacle for a large number of drugs [108-110]. Thus, drug-loaded PEG-coated nanoparticles that specifically accumulate in the brain could be especially helpful for the treatment of disseminated and very aggressive brain tumors.

However, it was shown that the PEG-coating only delayed MPS accumulation. Plasma protein adsorption could not be completely prevented, even at the highest PEG-coating layer thickness and density. No surface was yet designed to completely avoid protein adsorption. A challenging research topic is the design of new biomaterials with tailored properties to further reduce the interaction with blood components and MPS. Efforts are directed toward the "biomimetic" approach, which imitates the strategy used by pathogenic agents to escape MPS.

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