Nanocarrier

Torchilin, V. P. (2006). Multifunctional nanocarriers. Advanced Drug Delivery Reviews, Vol. 58, 14, (December 2006), pp. (1532-1555), ISSN 0169-409X Tran, V. T., Benoit, J. P. Venier-Julienne, M. C. (2011). Why and how to prepare biodegradable, monodispersed, polymeric microparticles in the field of pharmacy International Journal of Pharmaceutics, Vol. 407,1-2, (December 2011), pp. (1-11), ISSN 0378-5173... 

Numerous experimental therapeutics have shown potency in vitro however, when they are tested in vivo, they often lack significant efficacy. This is often attributed to unfavorable pharmacokinetic properties and systemic toxicity, which limit the maximum tolerated dose. These limitations can be overcome by use of drug carriers. Two general types of carrier systems have been designed drug conjugation to macromolecular carriers, such as polymers and proteins and drug encapsulation in nanocarriers, such as liposomes, polymersomes and micelles. 

This final class of ELPs is used in nanocarriers and in dmg depots. In this section, the emphasis will be on systems that have already been tested in vivo, and on some recent promising developments in the area of ELP-assisted dmg delivery. 

Micellar nanocarriers have already been applied successfully for delivery of hydro-phobic drugs [86]. These carriers are usually the product of self-assembled block copolymers, consisting of a hydrophilic block and a hydrophobic block. Generally, an ELP with a transition temperature below body temperature is used as hydrophobic block and the hydrophilic block can be an ELP with a transition temperature above body temperature or another peptide or protein. The EPR effect also directs these types of carriers towards tumor tissue. 

Neu M, Germershaus O, Mao S, Voigt KH, Behe M, Kissel T (2007) Crosslinked nanocarriers based upon poly(ethylene imine) for systemic plasmid delivery in vitro characterization and in vivo studies in mice. J Control Release 118 370-380... 

Fig. 30 Types of nanocarriers for drug delivery, (a) Polymeric nanoparticles polymeric nanoparticles in which drugs are conjugated to or encapsulated in polymers, (b) Polymeric micelles amphiphilic block copolymers that form nanosized core-shell structures in aqueous solution. The hydrophobic core region serves as a reservoir for hydrophobic drugs, whereas hydrophilic shell region stabilizes the hydrophobic core and renders the polymer water-soluble.

Fig. 29. A schematic representation of a copper-based radiopharmaceutical encapsulated in a tailored multifunctional nanocarrier.

The same group reported the simultaneous radiolabeling (with DOTA-anchored 4Cu) and fluorescence studies, coupled with biodistribution in vivo and in vitro (92). It is believed that appropriately functionalized SWNTs can efficiently reach tumor tissues in mice with no apparent toxicity (159). Furthermore, water-solubilised carbon nanotubes are nontoxic when taken up by cells even in high concentration (92). These studies have been complemented by the recent PET imaging of water-soluble 86Y labelled carbon nanotubes in vivo (mice) (160,161), to explore the potential usefulness of carbon nanocarriers as scaffolds for drug delivery. The tissue biodistribution and pharmacokinetics of model DOTA functionalized nanotubes have been explored in vivo (mouse model). MicroPET images indicated accumulation of activity mainly in the kidney, liver, spleen, and to a much less... 

For some examples, see e.g. (a) Hogan CF, Harris AR, Bond AM et al (2006) Electrochemical studies of porphyrin-appended dendrimers. PhysChemChemPhys 8 2058-2065 (b) Jang W-D, Nishiyama N, Zhang G-D et al (2005) Supramolecular nanocarrier of anionic dendrimer porphyrins with cationic block copolymers modified with polyethylene glycol to enhance intracellular photodynamic efficacy. Angew Chem Int Ed 44 419 -23 (c) Loiseau F, Campagna S, Hameurlaine A et al (2005) Dendrimers made of porphyrin cores and carbazole chromophores as peripheral units. Absorption spectra, luminescence properties, and oxidation... 

Nishiyama N (2007) Nanomedicine - Nanocarriers shape up for long life. Nat Nanotechnol 2 203-204. 

When targeting to lung is considered, once again nanoparticles have an upper hand. Particulate nanocarriers are extremely advantageous because of avoidance of macrophage clearance mechanisms and long residence times (Dailey et al, 2006). 

A. Garcia-Bernabe, M. Kramer, B. Olah, R. Haag, Syntheses and phase-transfer properties of dendritic nanocarriers that contain perfluorinated shell structures, Chem. Eur. J. 10 (2004) 2822-2830. 

Dziubla, T.D., Karim, A., Muzykantov, V.R. (2005). Polymer nanocarriers protecting active enzyme cargo against proteolysis. Journal of Controlled Release, 102, 427 139. 

An attractive strategy to improve CNS drug delivery is to link a nontransportable drug with a vector to the BBB. These moieties can work as molecular Trojan horses to transport across the BBB attached proteins, DNA molecules, and drug micro- and nanocarriers facilitating their penetration through the BBB. The choice of a vector moiety and a type of a linker is crucial for the success of this method of drug delivery. 

Suh J, Wirtz D, Hanes J (2004) Real-time intracellular transport of gene nanocarriers studied by multiple particle tracking. Biotechnol Prog 20 598-602... 

Rawat, M., D. Singh, et al. (2006). Nanocarriers promising vehicle for bioactive drugs. Biol Pharm Bull 29(9) 1790-8. 

---