These traditional particles have several disadvantages as vehicles for drug delivery. They are very quickly captured by the RES (half-life is less than 30 min). They are also instable; therefore, they cannot be used as a delivery agent without modification (Torchilin 2005). The introduction of PEG as a coating on liposomes, as seen in Fig. 4, has prolonged their circulation times in the bloodstream (half-life is about 5 h (Klibanov et al. 1990)) and these vehicles can be targeted to solid tumor sites by the EPR effect (Yokoyama 2005).
PEG is a hydrophilic, nonionic polymer that has been shown to exhibit excellent biocompatibility. PEG molecules can be added to the particles via a number of different routes including covalent bonding, mixing during nanoparticle preparation,
Fig. 4 Schematic illustration of a PEG-coated, drug-loaded liposome nanoparticle
Fig. 4 Schematic illustration of a PEG-coated, drug-loaded liposome nanoparticle or surface adsorption (Hans and Lowman 2002). Why can PEG coatings prolong liposome circulation time? It has been proposed that there are two main factors that affect the affinity of liposomes to the RES: nonspecific hydrophobic interactions of liposomes with RES cells and a specific opsonization reaction involving some blood component(s) such as immunoglobulin, complement proteins, apolipopro-teins, and fetuin (Moghimi and Hunter 2001). PEG-coated liposomes may become more hydrophilic, therefore their nonspecific interactions with RES cells are decreased. Specific interactions with opsonizing proteins are also reduced as PEG, as a coating layer, may act as a shield for liposomes. More interestingly, coating liposomes with PEG can also be designed so that after the PEG-coated liposomes reach the tumor site through the EPR effect, the local conditions of tumor tissues (e.g., acidic pH in tumors) will allow the PEG coating to become detached, promoting intracellular delivery of the drug payload, delivery of oligonucleotides, or delivery of genes (Zalipsky et al. 1999) (Fig. 4).
Was this article helpful?
Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...