Liposomes proteins

Bz s-imidoesters like DMS may be used to couple proteins to PE-containing liposomes by crosslinking with the amines on both molecules (Figure 22.24). However, single-step crosslinking procedures using homobifunctional reagents are particularly subject to uncontrollable polymerization of protein in solution. Polymerization is possible because the procedure is done with the liposomes, protein, and crosslinker all in solution at the same time. 

Rao M, Alving CR. Delivery of lipids and liposomal proteins to the cytoplasm and Golgi of antigen-presenting cells. Adv Drug Deliver Rev 2000 41 171. 

Rao M, et al. Trafficking of liposomal antigen to the trans-Golgi of murine macrophages requires both liposomal lipid and liposomal protein. Exp Cell Res 1999 246 203. 

Component of liposomes Protective coating for liposomes Protein stabilizer DNA transfection agent Surfactant in intranasal or ocular delivery Increasing susceptibility of tumor cells to cytotoxic drugs Liver gene delivery... 

Most approaches are based on combinations of the drug with a polymer. The latter serves as a carrier system wherein the drug is dispersed or dissolved, or to which it is covalently linked. Cells, microspheres, nanospheres, liposomes, proteins, antibodies, hormones, natural and synthetic... 

Liposome Protein transferred (%) Lipid recovered (%) Protein/Lipid (by wt)... 

For completeness we note that two other FFF subtechniques can be applied to certain polymeric materials, although applications are so far limited. Sedimentation FFF is the most notable example. For this system the driving force (centrifugally induced sedimentation) is directly proportional to molecular mass in a form that is calculable from first principles (see eqn 8.7). Accordingly, molecular mass distributions can in theory be obtained by calculation without empirical calibration. This principle has been successfully applied to the determination of the molecular mass and particle size distribution of numerous colloidal particles including viruses, latices, emulsions, liposomes, protein aggregates, and water-borne colloids [5,7,9]. However, as noted earlier, sedimentation FFF is not applicable to many polymers of interest because sedimentation forces (even in a powerful centrifuge) are not adequate to drive the components to the accumulation wall of the FFF channel. Thus molecular masses of less than 10 cannot be well... 

ESPT reactions are affected by environmental conditions. The ESPT behaviors of aromatic molecules in various organized media such as liposomes, proteins, cyclodextrins, polymers, sol-gel glasses, monolayers, LB films, and solids have been reviewed by Mishra [3]. 

Margulis, B.A., Sandler, S., Eizirik, D.L., Welsh, N., Welsh, M. (1991). Liposomal delivery of purified heat shock protein hsp70 in rat pancreatic islets as protection against interleukin I beta-induced impaired beta cell function. Diabetes 40, 1418-1422. 

Delivery of peptides and proteins via the gastrointestinal tract has not been successful because of poor penetration through the intestinal epithelium and high levels of proteolytic activity in the gastrointestinal tract. Liposomal encapsulation of proteins and peptides will not improve the efficiency and capacity of this absorption pathway considerably (e.g., Ryman et al., 1982 Machy and Leserman, 1987 Weiner and Chia-Ming Chiang, 1988). These difficulties in delivery via the oral route caused the parenteral route to remain the preferred route for the administration of therapeutic peptides... 

A notable property of liposomes, which has not been appreciated enough, is the presence of water inside liposomes. This makes them an excellent delivery system for biotechnologically engineered proteins with tertiary and quanternary structures which are sensitive to irreversible damage induced by dehydration, as often occurs with alternative, particulate carrier systems. 

Jiskoot, W., Teerlink, T., Van Hoof, M. M. M., Bartels, K., Kanhai, V., CrommeUn, D. J. A., and Beuvery, E. C. (1986b). Immunogenic activity of gonococcal protein I in mice with three different lipoidal adjuvants delivered in liposomes and in complexes, Inf. Immun.. 54. 333-338. 

Scherphof, G., Damen, J., and Hoekstra, D. (1981). Interactions of liposomes with plasma proteins and components of the immune system, in Liposomes From Physical Structure to Therapeutic Applications (C. G. Knight, ed.), Elsevier, Amsterdam, pp. 299-322. 

Numerous experimental therapeutics have shown potency in vitro however, when they are tested in vivo, they often lack significant efficacy. This is often attributed to unfavorable pharmacokinetic properties and systemic toxicity, which limit the maximum tolerated dose. These limitations can be overcome by use of drug carriers. Two general types of carrier systems have been designed drug conjugation to macromolecular carriers, such as polymers and proteins and drug encapsulation in nanocarriers, such as liposomes, polymersomes and micelles. 

In this chapter we describe the basic principles involved in the controlled production and modification of two-dimensional protein crystals. These are synthesized in nature as the outermost cell surface layer (S-layer) of prokaryotic organisms and have been successfully applied as basic building blocks in a biomolecular construction kit. Most importantly, the constituent subunits of the S-layer lattices have the capability to recrystallize into iso-porous closed monolayers in suspension, at liquid-surface interfaces, on lipid films, on liposomes, and on solid supports (e.g., silicon wafers, metals, and polymers). The self-assembled monomolecular lattices have been utilized for the immobilization of functional biomolecules in an ordered fashion and for their controlled confinement in defined areas of nanometer dimension. Thus, S-layers fulfill key requirements for the development of new supramolecular materials and enable the design of a broad spectrum of nanoscale devices, as required in molecular nanotechnology, nanobiotechnology, and biomimetics [1-3]. 

S-layer protein was crystallized on lipid monolayers lipid bilayer membranes and liposome. 

In order to enhance the stability of hposomes and to provide a biocompatible outermost surface shucture for controlled immobihzation (see Section IV), isolated monomeric and oligomeric S-layer protein from B. coagulans E38/vl [118,123,143], B. sphaericus CCM 2177, and the SbsB from B. stearothermophilus PV72/p2 [119] have been crystallized into the respective lattice type on positively charged liposomes composed of DPPC, HD A, and cholesterol. Such S-layer-coated hposomes are spherical biomimetic structures (Fig. 18) that resemble archaeal ceUs (Fig. 14) or virus envelopes. The crystallization of S-... 

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