Protein release kinetics

Park,T. G., Lu, W., and Crotts, G. (1995), Importance of in vitro experimental conditions on protein release kinetics, stability and polymer degradation in protein encapsulated poly(D,L-lactic acid-co-glycolic acid) microspheres,/. Controlled Release, 33,211-222. 

An important factor complicating the recovery of recombinant proteins from Escherichia coli is their intracellular location. An alternative to the commonly used method of releasing these proteins by mechanical disruption is to chemically permeabilize the cells. The objective of this research was to characterize the protein release kinetics and mechanism of a permeabiliza-tion process using guanidine-HCl and Triton-XIOO. The protein release kinetics were determined as a function of the guanidine, Triton, and cell concentrations. Some of the advantages over mechanical disruption include avoidance of extensive fragmentation of the cells and retention of the nucleic acids inside the cell structure. 

However, there are drawbacks observed in protein-loaded microspheres. The protein release kinetics exhibits an initial fast release followed by a slow release, resulting in an incomplete protein release despite significant degradation of microspheres (36). The very slow release kinetics was attributed to the protein aggregation and nonspecific adsorption within the microspheres. It was found that the protein... 

Haidar, Z.S., Hamdy, R.C. and Tabiizian, M. (2008) Protein release kinetics for core-shell hybrid nanoparticles based on the layer-by-layer assembly of alginate and chitosan on liposomes. Birwnaterials, 29, 1207-1215. 

Agrawal, C.M., Best, D., Heckraann, J.D., Boyan, B.D. (1995) Protein release kinetics of a biodegradable implant for fracture non-unions. Biomaterials, 16, 1255-1260. 

F. Ungaro, M. Biondi, I. dAngelo, L. Indolfi, F. Quagha, P.A. Netti, et al. Microsphere-integrated collagen scaffolds for tissue engineering Effect of microsphere formulation and scaffold properties on protein release kinetics. Journal of Controlled Release, 113, 128-36, 2006. 

Jiang, G. et al.. Assessment of protein release kinetics, stability and protein polymer interaction of lysozyme encapsulated poly(D,L-lactide-co-glycolide) microspheres,/. Control. Release,79,137, 2002. 

Haidar, Z. S., Hamdy, R. C., Tabrizian, M. Protein Release Kinetics for Core-shell Hybrid Nanoparticles Based on the Layer-by-layer Assembly of Alginate and Chito-san on Liposomes. Biomaterials, 2008,29,1207-1215. 

Because of the extreme differences between conventional pharmaceuticals and the protein molecules in terms of formulation techniques and drug release kinetics, the two categories will be discussed separately here. 

On the level of kinetics it is interesting to note that activation of G proteins by receptors appears to be rather slow. For example, in the case of -adrenergic receptors and G , the comparison of receptor—G protein interaction kinetics, which occur with time constants of 30—50 ms (Hein et al, 2005), with the kinetics of G activation, which require 0.5-1 s (Biinemann et al, 2003), reveals that the G proteins may be a time-limiting step in this signaling pathway. It remains to be seen whether the release of GDP from the a subunit, which is induced by the agonist-occupied receptor, is indeed the reason for the slow kinetics of G protein activation, as may be inferred from biochemical experiments in cell membranes and in reconstituted systems. 

A sustained drug release is favourable for drugs with short elimination half-life. It can be controlled by hydration and diffusion mechanisms or ionic interactions between the drug and the polymeric carrier. In the case of diffusion control the stability of the carrier system is essential, as its disintegration leads to a burst release. Therefore, the cohesiveness of the polymer network plays a crucial role in order to control the release over several hours. Due to the formation of disulphide bonds within the network thiomers offer adequate cohesive stability. Almost zero-order release kinetics could be shown for insulin embedded in thiolated polycarbophil matrices (Clausen and Bernkop-Schnurch 2001). In the case of peptide and protein drugs release can be controlled via ionic interactions. An anionic or cationic polymer has to be chosen depending... 

Furfine, E.S., Leban, J.J., Landavazo, A., Moomaw, J.F., and Casey, P.J. (1995). Protein farnesyltransferase kinetics of farnesyl pyrophosphate binding and product release. Biochemistry 34 6857-6862. 

Crotts, G. Park, T.G. Protein delivery from poly(lactic-co-glycolic acid) biodegradable microspheres release kinetics and stability issues. J. of Microencap. 1998,15 (6), 699-713. 

Despite the extensive use of PLGA polymers in the microencapsulation arena, it has been found through decades of research that the PLGA microparticle systems are not universally suited for different applications. One of the limitations in the prevalent PLGA systems is that bulk hydrolysis of the polymer induces acidification of microenvironment of the microparticles, which can be detrimental to various payloads such as proteins and nucleic acids. In addition, their drug release kinetics are not readily tunable and, thus, are inappropriate for specific applications.f ... 

Numerous biomarkers have been monitored to assess myocardial injury. Most are myocardial proteins and differ in their (1) location within the myocyte, (2) release kinetics after damage, and (3) clearance from the circulation. A number of other molecules also are thought to have potential as biomarkers. 

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