Intracellular delivery

Colin M, Maurice M, Trugnan G, et al. Cell delivery, intracellular trafficking and expression of an integrin-mediated gene transfer vector in tracheal epithelial cells. Gene Ther 2000 7(2) 139-152. 

Our initial bioavailabihty experiments indicate that cationic aPNAs are readily intemahzed by cells without any additional delivery vehicle and that they do not affect ceU viabihty. We are currently examining aPNA internalization with other cell types as weU as the intracellular localization of aPNAs. 

Holowka EP, Sun VZ, Kamei DT, Deming TJ (2007) Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. Nat Mater 6 52... 

Upadhyay KK, Bhatt AN, Mishra AK, Dwarakanath BS, Jain S, Schatz C, Le Meins JE, Earooque A, Chandraiah G, Jain AK, Misra A, Lecommandoux S (2010) The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(y-benzyl L-glutamate)-b-hyaluronan polymersomes. Biomaterials 31(10) 2882... 

Decreased cerebral blood flow, resulting from acute arterial occlusion, reduces oxygen and glucose delivery to brain tissue with subsequent lactic acid production, blood-brain barrier breakdown, inflammation, sodium and calcium pump dysfunction, glutamate release, intracellular calcium influx, free-radical generation, and finally membrane and nucleic acid breakdown and cell death. The degree of cerebral blood flow reduction following arterial occlusion is not uniform. Tissue at the... 

Williamson, J.M., Boettcher, B. and Meister, A. (1982). Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis. Proc. Natl Acad. Sci. USA 79, 6246-6249. 

Synthetic Polymers. Synthetic polymers are versatile and offer promise for both targeting and extracellular-intracellular drug delivery. Of the many soluble synthetic polymers known, the poly(amino acids) [poly(L-lysine), poly(L-aspartic acid), and poly(glutamic acid)], poly(hydroxypropylmethacrylamide) copolymers (polyHPMA), and maleic anhydride copolymers have been investigated extensively, particularly in the treatment of cancers. A brief discussion of these materials is presented. 

McGuigan C, Pathirana RN, Balzarini J, De Clercq E. Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT. J Med Chem 1993 36 1048-1052. 

Puech F, Gosselin G, Lefebvre I, Pompon A, Aubertin A-M, Kirn A, Im-bach J-L. Intracellular delivery of nucleoside monophosphates through a reductase-mediated activation process. Antiviral Res 1993 22 155-174. 

Lipophorin acts as a reusable shuttle between the membrane-bound lipophorin receptors in tissues (Tsuchida and Wells 1990, Gopalapillai et al. 2006) and is not generally endocytosed in the cells (Law and Wells 1989, Arrese et al. 2001, Canavoso et al. 2001). Thus, the intracellular CBP alone seems not to be able to pick up carotenoid from the lipophorin that resides outside of the cell. Cell surface components are thought to be necessary to allow intracellular delivery of carotenoids (Figure 24.6, magnification) (Arrese et al. 2001). The lipid transfer particle (LTP) (Blacklock and Ryan 1994, Tsuchida et al. 1997) on the outer surface of membranes and unknown membrane-spanning factors that specifically transfer carotenoids might be candidates. 

Other types of branched peptide dendrimers, known as multiple antigen peptides (MAPs), have been synthesized to mimic proteins for applications, for instance as synthetic vaccines, serodiagnostics, peptide inhibitors and intracellular delivery vehicles. Since this concept has been recently described in detail elsewhere [11], only the conceptual framework will be briefly presented here. Tam and coworkers have developed a dendritic core based on lysine units for the construction of MAPs [12-15] (Fig. 3). Carrying antigens at their periphery these MAPs have been designed to increase antigenicity and immunogenicity of peptides. 

Derossi D, Chassaing G, Prochiantz A. Trojan peptides the penetratin system for intracellular delivery. Trends Cell Biol 1998 8 84-87. 

Remaut, K., Lucas, B., Braeckmans, K., Sanders, N. N., De Smedt, S. C. and Demeester, J. (2005). FRET-FCS as a tool to evaluate the stability of oligonucleotide drugs after intracellular delivery. J. Control Release 103, 259-71. 

Clark H.A., Kopelman R., Tjalkens R., Philbert M.A., Optical Nanosensors for Chemical Analysis inside Single Living Cells. 1. Fabrication, Characterization, and Methods for Intracellular Delivery of PEBBLE Sensors, Anal. Chem. 1999 71 4831— 4836. 

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