Protein delivery applications

Tsuda Y, Kikuchi A, Yamato M et al (2005) The use of patterned dual thermoresponslve surfaces for the collective recovery as co-cultured cell sheets. Biomaterials 26 1885-1893 Tsuda Y, Shimizu T, Yamato M et al (2007) Cellular control of tissue architectures using a three-dimensional tissue fabrication technique. Biomaterials 28 4939 946 Van Tomme SR, Hennink WE (2007) Biodegradable dextran hydrogels for protein delivery applications. Expert Rev Med Devic 4 147-164... 

Liu et al. (2005) have prepared hydrophobic chitosan nanoparticles with linoleic acid for protein delivery. Linoleic acid is an essential fatty acid that exists as a positional and stereoisomer of octa-decadienoic acid, and this type of polyunsaturated fatty acid can sensitize tumour cells to chano-therapy and radiotherapy. This has been proved in cell culture, tumour-bearing animals, and, finally, in humans (Conklin 2002, Germain et al. 1998, Vartak et al. 1997). Linoleic acid plays a mryor role in fatty acid metabolism in the human body. Liu et al. have developed biocompatible amphiphilic lenoleic acid chitosan nanoparticles (100-500 nm), which can be used for protein delivery applications. The loading efficiency decreases with increasing concentration of Bovine Serum Albumin (BSA), and the nanoparticles are saturated with BSA that has a concentration of 0.5mg/mL and a loading capacity of 37.57% 0.25%. BSA forms complexes with a derivative that has a hydrophilic chitosan backbone and a hydrophobic domain of linoleic group. 

Physically crosslinked HA hydrogel containing vasoactive intestinal peptide-loaded liposomes was developed for the treatment of endotoxin-induced uveitis. Interactions between HA chains and liposomes increased the viscosity of the gel and resulted in a delayed release of the vasoactive intestinal peptide [87]. However, the low stability of HA microparticles and physically crosslinked HA hydrogel is a limitation for protein delivery applications. 

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. 

Polyphosphazenes are a relatively new class of biodegradable polymers. Their hydrolytic stability or instability is determined not by changes in the backbone structure but by changes in the side groups attached to an unconventional macromolecular backbone. Synthetic flexibility and versatile adaptability of polyphosphazenes make them unique for drug delivery applications. For example, Veronese et al.18 prepared polyphos-phazene microspheres with phenylalanine ethyl ester as a phosphorous substituent and loaded it with succinylsulphathiazole or naproxen. The kinetics of release from these matrices were very convenient in yielding local concentrations of the two drugs that are useful per se or when mixed with hydroxyapatite for better bone formation. Polyphosphazene matrices are also considered as potential vehicles for the delivery of proteins and vaccines.19... 

Pan Y, Li YJ, Zhao HY, Zheng JM, Xu H, Wei G, Hao JS, Cui FD (2002) Bioadhesive polysaccharide in protein delivery system chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int J Pharm 249(1-2) 139-147 Park K, Robinson JR (1984) Bioadhesive polymers as platforms for oral-controlled drug delivery method to study bioadhesion. Int J Pharm 19 107-127 Patel H, Ryman BE (1981) Systemic and oral administration of liposomes. In Knight CG(ed) Liposomes From Physical Structure To Therapeutic Applications, Elsevier, Amsterdam, pp 409-441... 

These attributes make the buccal mucosa ideally suited for sustained-delivery applications, delivery of poorly permeating molecules, and perhaps peptide and protein drags. Such formulations include ... 

Prokop A, Kozlov E, Newman GW, Newman MJ (2002) Water-based nanoparticulate polymeric system for protein delivery Permeability control and vaccine application. Biotechnol Bioeng, accepted... 

The encapsulation of hepatocytes for a bioartificial liver, and cell therapy for the treatment of other hormone deficiencies or neurodegenerative diseases, such as Alzheimer s and Parkinson s, are also under investigation. Additional examples of cell encapsulation in polymer-polymer coacervates include non-autologous gene therapy,blood substitutes as well as the treatment of prostate cancer. Pharmaceutical applications of microcapsules encompass, in addition, trans-dermal drug delivery and protein delivery such as is required in anti-inflammatory therapy for arthritis. 

Finally, pulmonary protein delivery has advanced tremendously since 1990. One local therapy has been approved and a number of others, including insulin, are in the later stages of clinical development. The device platforms that have been developed for these macromolecules have also exhibited higher delivery efficiencies and greater reproducibility than the old technologies, and these attributes may well have application in other areas of pulmonary delivery. For example, they may facilitate delivery of small molecules though the lung for a faster onset of action. 

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