Immune system targeted delivery systems

Systemic targeting of pDNA and siRNA polyplexes has been demonstrated in several animal models. In continuation of the work with localized antiproliferative and immunostimulatory poly(I C) RNA, intravenous systemic delivery of EGER-targeted PEG-modified polyplexes were successfully used for human carcinoma treatment in mice [225]. The therapeutic effect was most pronounced when intravenous delivery of poly(I C) polyplexes was followed by intraperitoneal injection of peripheral blood mononuclear cells [226]. This induced the complete cure of SCID mice with pre-established disseminated EGFR-overexpressing tumors, without adverse toxic effects. Due to the chemokines produced by the internalized poly (I C) in the tumor cells, the immune cells home to the tumors of the treated animal and contribute to the tumor destruction. 

The concept of de-PEGylation can be applied to the development of nanoparticle-based drug delivery systems. PEG is used for the modification of liposomes to increase their blood circulation time [38], However, it also prevents cellular uptake, resulting in a decrease in therapeutic efficiency thus, modifications of the liposome surface with PEG interfere with membrane fusion to the cell membrane and liposome decomposition [39]. One of the possible strategies to solve this problem is to cleave the PEG chains after the nanoparticle reaches the target site (Fig. 9). This system of de-PEGylation of liposomes is also useful in avoiding the immune... 

As of today, there are no commercially available pharmaceutical products of this technology. The pharmaceutical industry however, is involved in developing nanoparticle-based delivery systems. Use of nanospheres to modify the blood-brain barrier (BBB)—limiting characteristics of the drug enables targeted brain delivery via BBB transporters and provides a sustained release in brain tissue and vaccine delivery systems to deliver therapeutic protein antigens into the potent immune cells are under investigation.103... 

Synthetic pathways that supposedly avoid the pitfalls of viral delivery systems (see below) have been explored. Both Kaneda and coworkers (Chapter 9) and Sorgi and coworkers (Chapter 8) have been successful in designing viruslike liposomal delivery systems that provide some of the advantages of viral carriers—in other words, cell surface recognition and fusion with target cells (or intracellular compartments, i.e., endosomes, respectively)—without the detrimental immune response that viral systems generate. The efficiency of these systems is still orders of magnitude less than that of viral carriers however, cytotoxic... 

The lung comprises about 40 different cell types, amongst which type I and type II alveolar epithelial cells are the major types targeted by pulmonary drug delivery systems. Type I cells play an important role in the absorption process of proteins, while type II cells produce surfactant, regulate the immune response, and serve... 

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