Proteins delivery systems

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... 

Pan, Y., et al. 2002. Bioadhesive polysaccharide in protein delivery system chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int J Pharm 249 139. 

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... 

Tracy, M. A. (1998), Development and scale-up of a microsphere protein delivery system, Biotechnol. Prog., 14,108-115. 

Gao, H., Wang, Y. N. Fan, Y. G., and Ma, J. B. (2006), Conjugates of poly(DL-lactic acid) with ethylenediamino or diethylenetriamino bridged bis(P-cyclodextrin)s and their nanoparticles as protein delivery systems, / Controlled Release, 112,301-311. 

Zeng J et al (2005) Polyfvmyl alcohol) nanofibers by electrospinnmg as a protein delivery system and the retardation of enzyme release by additional polymer coatings. Biomacromolecules 6(3) 1484—1488... 

A subcutaneously implantable protein delivery system made up of a DUROS osmotic pump containing dry (lyophilized or spray-dried) protein formulations in nonaqueous suspending vehicle is being developed for long-term release of proteins at the target site. The duration of protein release can be... 

Cleland, J.L., Daugherty, A., and Mrsny. R., Emerging protein delivery systems. Current opinion in Biotechnology, 12, 21, 2001. 

MorphoGen Pharmaceuticals (San Diego, CA) Pluripotent stern cells and matrix protein delivery systems Preclinical... 

To develop a targeted protein delivery system, a functional domain (the therapeutically active protein) has to be connected to a targeting domain, which directs the therapeutic protein to the site of desired action, i.e., tumor tissue. In... 

Reduction of the disulfide bond in the thiol-rich environment, resulting in the release of the entrapped protein, was also the working principle of another intracellular protein delivery system. The DDS was based on linear polyamidoamines (PAAs) that formed a PEC with negatively charged human serum albumin (HSA). The PEC showed mucoadhesive properties and released the immobilized HSA under intracellular conditions due to the cleavage of the disulfide bonds, while the complex was stable under extracellular conditions. This resulted in enhanced uptake by exposed human-derived intestinal Caco-2/TC7 cells and HT29-MTX mucus/ secreting cells. 

Seeherman H, Wozney J, Li R. Bone morphogenetic protein delivery systems. Spine. 2002 27(16 Suppl l) S16-23. 

Papadimitriou SA, Achillas DS, Bikiaris DN (2012) Chitosan-g-PEG nanoparticles ionically crosslinked with poly(glutamic acid) and tripolyphosphate as protein delivery systems. Int J Pharm 430 318-327... 

Su ZQ, Zhanh HL, Wu SH et al (2010) Preparation and characterization of water-soluble chitosan nanoparticles as protein delivery system. J Nanomater. doi 10.1155/2010/898910... 

Gao H, Wang YN, Fan YG et al (2005) Synthesis of a biodegradable tadpole-shaped polymer via the coupling reaction of polylactide onto mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin and its properties as the new carrier of protein delivery system. J Control Release 107 158-173... 

Porous chitosan has recently been evaluated as a protein delivery system by Cardinal et al. (1990). Sustained release was demonstrated for bovine growth hormone, alkaline phosphatase, and BSA. Treatment of dried particles of chitosan with methanol for brief periods extended release duration, with a 10-min treatment increasing the time required for 50% release of BSA from <1 day to 2 weeks. Jamas et al. (1991) have documented preparations of P-glucan microparticles, where time to 50% release ranged from 30min for cytochrome c (MW 14,000) to 200 min for alcohol dehydrogenase (MW 150,000). 

Due to the well-known enzymatic lability or environmental sensitivity of proteins, a common characteristic among protein delivery systems is the ability to protect the protein from the external environment. Modes of protection may be chemical or physical. A well-recognized system that provides physical protection of proteins is microcapsules, in which a solid membrane separates the solid contents of the microcapsule from the external environment. An alternative approach would be to replace a solid membrane with a liquid membrane, i.e., multiphase or multiple emulsions. Multiple emulsions may be prepared as either oil-in-water-in-oil (OAV/0) or water-in-oil-in-water (W/OAV) systems. Multiple-emulsion systems, for the purpose of delivering proteins, would be comprised of an interior aqueous phase, containing the water-soluble protein, separated from the external aqueous phase by an oil phase, i.e., W/OAV emulsions (Fig. 1). Multiple emulsions, therefore, provide an alternative technique for the encapsulation of proteins and other materials that would otherwise be metabolized, rapidly cleared, or toxic to the patient. Multiple emulsions have been utilized for parenteral and oral administration (Brodin et al, 1978). Although there is a physical resemblance to microcapsules, multiple... 

Multiple emulsions are unique in that a true liquid phase is maintained separate from an external aqueous phase. This may be especially important for bioactive molecules that cannot be appropriately stabilized in the solid state. In addition, the separation of aqueous phases enables highly specialized environments, conducive to protein activity, to be prepared. The physical instability of conventional systems remains a major factor limiting their wider application. Attempts to improve the physical stability of the aqueous dispersions through interfacial complexation and the use of microemulsions are improving the short-term stability. As an alternative approach, solid-state emulsions attempt to store the multiple emulsion as a solid. Although solid-state emulsions appear to have the potential to be useful protein delivery systems, a substantial experimental data base has yet to be generated. 

---