Multifunctional delivery system

Chhablani et al. showed that in oxidized PSi covalently loaded daunorubicin demonstrated sustained intravitreal release for 3 months without any evidence of toxicity, while physisorbed daunorubicin was released within 2 weeks and localized retinal toxicity were observed due to high daunorubicin concentration. Wu et al. added a new functionality to PSi dmg delivery system (Wu et al. 2011). They used 1-dimensional porous silicon photonic crystal in intravitreal delivery. The reflectance spectrum of the crystal (i.e., color) changed from red to green as daunombicin was releasing enabling real-time monitoring of the drag release proeess. These types of multifunctional delivery systems based on versatile properties of PSi are expeeted to be published much more in future. 

The nanostructured molecular arrangements from DNA developed by Seeman may find applications as biological encapsulation and drug-delivery systems, as artificial multienzymes, or as scaffolds for the self-assembling nanoscale fabrication of technical elements. Moreover, DNA-protein conjugates may be anticipated as versatile building blocks in the fabrication of multifunctional supramolecular devices and also as highly functional-... 

Recent developments in polymer chemistry have allowed for the synthesis of a remarkable range of well-defined block copolymers with a high degree of molecular, compositional, and structural homogeneity. These developments are mainly due to the improvement of known polymerization techniques and their combination. Parallel advancements in characterization methods have been critical for the identification of optimum conditions for the synthesis of such materials. The availability of these well-defined block copolymers will facilitate studies in many fields of polymer physics and will provide the opportunity to better explore structure-property relationships which are of fundamental importance for hi-tech applications, such as high temperature separation membranes, drug delivery systems, photonics, multifunctional sensors, nanoreactors, nanopatterning, memory devices etc. 

The failure in increasing residence time of mucoadhesive systems in the human intestinal tract has led scientists to the evaluation of multifunctional mucoadhesive polymers. Research in the area of mucoadhesive drug delivery systems has shed light on other properties of some of the mucoadhesive polymers. One important class of mucoadhesive polymers, poly(acrylic acid) derivatives, has been identified as potent inhibitors of proteolytic enzymes [72-74]. The interaction between various types of mucoadhesive polymers and epithelial cells has a direct influence on the permeability of mucosal epithelia by means of changing the gating properties of the tight jrmctions. More than being only adhesives, some mucoadhesive polymers can therefore be considered as a novel class of multifunctional macromolecules with a number of desirable properties for their use as delivery adjuvants [72,75]. 

Nonviral vector systems are usually either composed of a plasmid based expression cassette alone ( naked DNA), or are prepared with a synthetic amphipathic DNA-complexing agent (84, 88). Gene delivery systems based on nonviral vectors mainly comprise cationic liposomes, DNA-polymer-protein complexes, and mechanic administration of naked DNA. An idealized/optimized multifunctional nonviral gene delivery system is depicted in Figure 13.4. 

FIGURE 13.4 An optimized/ideal multifunctional nonviral gene delivery system. 

Nishikawa M, Yamauchi M, Morimoto K et al (2000) Hepatocyte-targeted in vivo gene expression by intravenous injection of plasmid DNA complexed with synthetic multifunctional gene delivery system. Gene Ther 7(7) 548-555... 

FIGURE 8 Schematic for design of multifunctional drug delivery system (DDS) that includes pH-cleavable PEG-Hz-PE (a), temporarily shielded biotin or TATp (b), and monoclonal antibody (c) attached to surface of DDS via pH-noncleavable spacer. (Reprinted with permission from ref. 183. Copyright 2006 by the Americam Chemical Society.)... 

Tumor-Speckle MAbs or Fragments. In recent years, MAbs have been identified as effective anticancer agents. Several MAbs have been approved for clinical uses since 1997, and many more are in clinical trials. MAbs are believed to have multifunctional mechanisms. Their high selectivity toward tumors makes them ideal targeting ligands for actively tumor-targeted drug delivery systems. 

In spite of these formidable challenges, the attractiveness of oral route has fueled the exploration of an incredibly diverse set of strategies to deliver proteins and peptides and the subject has been exhaustively reviewed. The various approaches include permeation enhancers, enzyme inhibitors, mucoadhesives, multifunctional matrices that simultaneously incorporate the above strategies, enteric coatings that offer protection from the acidic environment of the stomach, encapsulation (liposomes, microspheres, and nanoparticles), pH-sensitive polymers, microemulsions, carriers (delivery agents), and protein modification either to simply enhance permeability or to exploit specific transporters. While proof-of-concept has been demonstrated with most of these delivery systems in animal... 

Among the several drug delivery systems, liposomes - phospholipid nanosized vesicles with a bilayered membrane structure - have drawn a lot of interest as advanced and versatile pharmaceutical carriers for both low and high molecular weight pharmaceuticals. At present, liposomal formulations span multiple areas, from clinical application of the liposomal drugs to the development of various multifunctional liposomal systems to be used in therapy and diagnostics. This chapter provides a brief overview of various liposomal products currently under development at experimental and preclinical level. 

Abiief review is presented of recent progress in antimicrobial dendrimers. Mention is made of how both speeifie interactions and non-specific interactions can be utilised to design multifunctional antimicrobial agents which might be more potent than their monofimctional cormterparts. Uses as novel dmg delivery systems are also mentioned. 24 refs. USA... 

We recently proposed a novel non-viral gene delivery system multifunctional envelope-type nano device (MEND) to realize Programmed Packaging [1-3]. The ideal MEND (see Fig. 8.1) consists of a condensed DNA core and a lipid envelope structure equipped with the various func-... 

Nasongkla N, Bey E, Ren J, Ai H, Khemtong C, Guthi JS, Chin SF, Sherry AD, Boothman DA, Gao J. 2006. Multifunctional polymeric micelles as cancer targeted, MRI ultra sensitive drug delivery systems. Nano Lett 6 2427 2430. 

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