Protein delivery

Over the last decades, several academic and industrial research programs have been focused on the development and production of appropriate biocompatible formulations that provide enhanced therapeutic performance. Three different strategies can be discerned that are applied separately or in combination (i) addition of excipients to proteins, such as protease inhibitors, penetration or absorption enhancers like bile salts, fatty acids, cyclodextrins or surfactants (ii) modification of the physicochemical properties of proteins, e.g. by attachment of lipophilic or hydrophilic moieties or (iii) incorporation of proteins into polymeric or liposomal delivery carriers. A variety of polymeric vectors has been developed and exploited for this purpose, including biodegradable nanoparticles, nanogels, micelles, polymer bioconjugates and soluble nanocomposites. These polymeric carriers are more extensively described in the following sub-sections. 

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PEG/PBT copolymers are also very good matrix materials for the release of growth factors in tissue engineering. Proteins have been delivered from PEG/PBT microspheres with preservation of protein delivery of complete activity. In the case of protein delivery from PLGA and poly(ortho ester) microspheres, the protein activity was significantly reduced. " ... 

V. H. L. Lee, Peptide and Protein Delivery, Marcel Dekker, New York, 1991. 

K. L. Audus and T. J. Raub, Biological Barriers to Protein Delivery, Plenum Press, New York, 1993. 

Polyacryldextran Biodegradable TDS for protein delivery Proteins (e.g., L-asparaginase)... 

Keyword Adjuvant Biodegradable nanoparticles Poly(y-glutamic acid) Protein delivery Vaccine... 

Yoshikawa T, Okada N, Oda A et al (2008) Development of amphiphilic y-PGA-nanoparticle based tumor vaccine potential of the nanoparticulate cytosolic protein delivery carrier. Biochem Biophys Res Commun 366 408 -13... 

Goda, N., Tenno, T., Inomata, K., Iwaya, N., Sasaki, Y., Shirakawa, M., and Hiroaki, H. (2007) LBT/ PTD dual tagged vector for purification, cellular protein delivery and visualization in living cells. Biochim. Biophys. Acta 1773, 141-146. 

Neutra, M. and Kraehenhuhl, J.P., Transepithelial transport of proteins by intestinal epithelial cells, in Biological Barriers to Protein Delivery, Audus, K.L. and Raub, T.J., Eds., Plenum Press, New York, 1993, pp. 107-129. 

Saunders LM, Hendren RW. Protein Delivery Physical Systems, Pharmaceutical Biotechnology, Vol. 10, Plenum Press, New York, 1997. 

Futaki S, Suzuki T, Ohashi W, et al. Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem 2001 276(8) 5836-5840. 

Barth, H., Roebling, R., Fritz, M. and Aktories, K., The binary Clostridium botulinum C2 toxin as a protein delivery systems. Identification of the minimal protein region necessary for interaction of toxin, J. Biol. Chem., 277, 5074—5081, 2002. 

Lee KY, Yuk SH (2007) Polymeric protein delivery systems. Prog Polym Sci 32 669-697... 

Kim B, Flamme KL, Peppas NA (2003) Dynamic swelling behavior of pH-sensitive anionic hydrogels for protein delivery. J Appl Polym Sci 89 1606-1613... 

A biopolymer-based drug carrier designed for protein delivery must meet the following requirements. In addition to controlling the release of drug, (1) the carrier must be biocompatible and degraded products must be nontoxic, (2) the carrier must incorporate the protein in a sufficiently gentle manner to retain bioactive conformation, and (3) the carrier must be able to incorporate the protein in pharmaceutical scale [12]. 

Woodley, J.F., Enzymatic barriers for GI peptide and protein delivery. Crit Rev Ther Drug Carrier Syst, 1994.11(2-3) 61-95. 

PUlai, O., V. Nair, R. Podnri, and R. Panchagnnla, Transdermal iontophoresis. Part IT. Peptide and protein delivery. Methods Find Exp Chn Pharmacol, 1999. 21(3) 229-40. 

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