Encapsulated molecules

Hammer and coworkers prepared PEG-h-PCL polymersomes entrapping DXR (Fig. 11a). The release of DXR from the polymersomes was in a sustained manner over 14 days at 37 °C in PBS via drug permeation through the PCL membrane, and hydrolytic degradation of the PCL membrane [228]. The release rate of encapsulated molecules from polymersomes can be tuned by blending with another type of block copolymer [229]. Indeed, the release rate of encapsulated DXR from polymersomes prepared from mixtures of PEG- -PLA with PEG- -PBD copolymers increased linearly with the molar ratio of PEG- -PLA in acidic media (Fig. lib). Under acidic conditions, the PLA first underwent hydrolysis and, hours later, pores formed in the membrane followed by final membrane... 

Rebek, J. Jr (2005) Simultaneous encapsulation Molecules held at close range. Angew. Chem., Int. Ed., 44, 2068-2078. 

The enzyme, normally in solution, is added and after aging either a thin film or a gel can be formed with the encapsulated molecules. Depending upon the acid used, the solution pH and other conditions, gelation can take from 1 min up to several days. The sol-gel matrix shows many advantages (i) the ability to entrap a large amount of enzyme, (ii) retention of the enzymatic activity due to the sufficiently mild conditions of the sol-gel process,... 

Since the environment of the cavity presented by 2 is spatially and electronically confined, physical properties of encapsulated molecules are expected to change to some extent, or even dramatically. In this section, the variable properties of guests in the cavity of cage 2 are discussed. 

Nature is full of complex constructions designed to encapsulate molecules within a defined space. At one extreme there are cells, enclosed within phospholipid bilayers, and sea dwelling algae like Emiliania huxleyi that are surrounded by calcium carbonate coccoliths which overlap to form an exoskeleton. On a smaller scale are iron storage proteins such as ferritin that are amorphous in the absence of metal ions but form globular structures once metals are bound. 

A highly original aim, synthesizing a supramolecular cube, was realized by Thomas and co-workers [13] who linked metal corners with bifunctional, rigid, linear spacers. The complete the metals coordination environment the corners were capped with [9]ane-S3 macrocycles. There is a central cavity but it is too small to encapsulate molecules of the size of proteins or genetic material. 

Moreover, the inner cavity of supramolecular capsules provides a discrete, well-defined environment ideally suited to investigate effects of compartmentalization and processes in confined spaces [8]. To realize technical applications as detection and stabilization of encapsulated molecules or their use as nano-sized reaction vessels, precise control of important factors such as size, stability, porosity of the walls, and functionalization of the inner surface have to be achieved [9-18]. Several capsules have been synthesized and a proof of principle for several applications has been provided, but in most cases their use is restricted to small guest molecules. The development of spacious architectures which are able to encapsulate several bulky molecules and are amenable for decoration of the inner surface with functional groups will constitute an important step on the way to functional systems. 

The free or polymer-bound bis(arene)metal complex can also react with metal atoms. Francis et al. (44) first published evidence that the siloxane-bound ic-complexes are converted to dimers and higher nuclearity clusters by additional metal atoms. Their experiments were conducted on quiescent thin liquid films of polymer applied to the optical window of a cryotip (see above, Small Scale Syntheses). Low nuclearity polymer-encapsulated molecules of Tin, Vn, Crn and Mon (n = 2-5) were inferred from quantitative studies of the metal atom aggregation process. The initial reaction appears to occur as follows ... 

Fig. 31 The X-ray structure of the M6L4 complex between ligand 38 and frans-palladium chloride units with an encapsulated molecule of DMSO...

One of the important differences between molecules in zeolite cages and species isolated in other matrices such as cyclodextrins [22], micelles [23], vesicles [24] and polymers [25] arises from the fact that the zeolite can be an active host and influence the structure and reactivity of the encapsulated molecules. The nature of the intra-zeolitic environment has been extensively studied and the influence of polarity, steric and electrostatic effects on encapsulated molecules is beginning to be well understood. 

In summary, it is dear that the zeolite is a novel host for the entrapment of molecules and the rigidity and the charged nature of the framework allow for steric and electrostatic effects on the encapsulated molecules. Isolation of entrapped molecules can also influence their reactivity. The interest in zeolites as hosts for electron-transfer reactions stems from a combination of properties, including... 

The rote of cholesterol in the fluidity of biological membranes is characterized as essential. Cholesterol is a silent molecule and in the case of lipid bilayers and liposomes it is included into bilayers to control the rate of the release of encapsulated molecules or to influence the stability of liposomes. The addition of cholesterol in lipid bilayers composed of DPPC, at concentrations more than 20%, results in the decrease of the Tin and elimination of the pretransition temperature. 

Dried reconstituted vesicles (DRV) are liposomes that are formulated under mild conditions and have the capability to entrap substantially high amounts of hydrophilic solutes (compared with other types of liposomes). These characteristics make this liposome type ideal for entrapment of labile substances, as peptide, protein or DNA vaccines and sensitive drugs. In this chapter, we initially introduce all possible types of DRV liposomes (in respect to the encapsulated molecule characteristics and/or their applications in therapeutics) and discuss in detail the preparation methodologies for each type. 

After assuring that the column has been saturated, load the liposome sample on the column and separate the liposomes from the nonliposome encapsulated molecules. 

PBS (phosphate buffered saline), pH 7.40 for liposome preparation (for cases in which empty liposomes are prepared). This buffer is also used as elution buffer, for cleaning ARSL (from non-encapsulated molecules) by gel filtration. In each liter, this buffer contains sodium phosphate (Sigma) 0.05 M, NaCl 150 mM and sodium azide (Sigma) 0.2 g (to a final concentration of 0.02% w/v for prevention of bacterial growth). Before adjusting the volume (to 1 L), the pH ofthe solution is adjusted to 7.40. 

Sephadex G-50 (medium) (Phase Separations, Pharmacia, Sweden). The solid is dispersed in PBS buffer for swelling and the dispersion is subsequently degassed under vaccum. Gel chromatography columns are packed and used for ARSL separation from non-encapsulated molecules (as described in detail in the following section). 

After separating liposomes from non-liposome encapsulated molecules, the amount of calcein (or CF) entrapped in a given volume of vesicles is determined as well as the amount of lipid in the same volume of the ARSL dispersion, as described in the following section. 

Straubinger RM, Hong K, Friend DS (1983) Endocytosis of liposomes and intracellular fate of encapsulated molecules encounter with a low pH compartment after internalization of coated vesicles. Cell 32 1096-1079... 

The concept behind the use of liposomes as carriers of drugs and macromolecules is related to an expected protection of the encapsulated molecules in the blood stream, an altered tissue distribution and pharmacokinetics, as well as an increased uptake into cells by mechanisms that are not normally available for these molecules. Some of these expectations have been verified through studies in various laboratories during the last few years. Such studies have shown that liposome encapsulation can alter drastically the pharmacokinetics and tissue disposition of the encapsulated substances, it can enhance their uptake into cells, and it can Increase their pharmacological efficacy. Several recent reviews have discussed these early results in considerable detail. 20... 

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