Properties of CPPs

An obvious drawback in the synthesis of CPPs and related tubular compounds is the strain energy, which relates to the bending of linear Jt-conjugated molecules into rings. In addition, the effects of bending on the physical properties of CPPs, compared to the linear compounds, are interesting. Therefore, the strain and electronic properties of [ ]CPPs ( = 4-20) will be briefly discussed based on density functional theory (DPT) calculations. 

Since the mid 1980 s, elear polypropylene (cPP) has been available, mainly on aecount of sorbitol-based clarifiers. Recently, a novel, high efficiency clarifier, based on a new ehemistry platform, has beeome commercially available. The weaknesses of the sorbitols, such as low thermal and ehemical stabihties, have been overcome while the requirements for a melt sensitive clarifier are maintained. The high efficacy and thermal and chemical stabilities of the high efficieney elarifier provide advantages with regard to melt proeessibility and end-use properties of cPP. 

Whereas the kinematic viscosity fx/p, the thermal diffusivity k/Cpp, and the diffusivity D are physical properties of the system and can therefore be taken as constant provided that physical conditions do not vary appreciably, the eddy coefficients E, Eh, and ED will be affected by the flow pattern and will vary throughout the fluid. Each of the eddy coefficients is proportional to the square of the mixing length. The mixing length will ... 

The amino acid sequences of haptides comprise hydrophobic and cationic residues with a net charge of +4 to +5 per 19 to 21 amino acids. It was proposed that haptides could be attracted to the anionic liposomes as well as the anionic cell membrane and that the hydrophobic properties of the haptide facilitate membrane translocation (106). Haptide uptake was reported to be energy independent, occurring at 4°C. The advantage of this peptide compared to CPP such as TAT and Antp, is that, unlike the virus-derived peptides, the haptides are not recognized as foreign antigens and do not induce cell transformation (106). However, haptides have also been found to accelerate fibrin clot formation and lack cell specificity (106). 

Several studies have been performed during the last two decades on CPPs which may function as carriers for different minerals, especially calcium. Published data on the effect of CPP/casein on mineral solubility and absorption are inconsistent, partly due to the diversity of the experimental approaches. Most of the findings in the literature that deal with the mineral absorption-stimulating effect of CPP are based on in vitro, in situ, cell culture or single meal studies. Majority of the studies have been done with rats and have provided considerable evidence for the potential effect of casein-derived phosphopeptides to improve mineral absorption. This potential is not limited to calcium but is also valid for zinc and iron, and possibly other elements that have not been investigated so far (FitzGerald, 1998). Furthermore, CPPs have been shown to have anticariogenic properties, based on their ability to localise amorphous phosphate in dental plaque (Reynolds, 1998). 

Selection of an optimal CPP for delivering a specific cargo into a particular cell type, especially in vivo, is not necessarily a trivial task. Until now there are relatively few studies devoted to the comparison of the cellular delivery efficiency of different CPPs and the correlation to their side effects such as cytotoxicity and membrane destabilizing properties. Comparative data of the delivery efficiency of CPPs in vivo are even more scarce. 

Phencyclidine (PCP), Ketamin, and MK-801 all block the N-methyl-D-aspartate (NMDA) receptor complex and are associated with schizophrenia-like symptoms through hypofunction of the gintamatergic nenrotransmission (Krystal et al., 1994 Olney and Farber, 1995). Other NMDA antagonists have psychotogenic properties, too (CPP, CPP-ene, CGS 19755). NMDA receptor hypofunction can explain schizophrenic positive and negative symptoms, cognitive deterioration and structural brain changes (Olney and Farber, 1995). 

A second method to prepare polyanhydride microspheres—via solvent removal—has also been developed. Polyanhydrides composed of the following diacids were used sebacic acid (SA), bis(p-carboxyphenoxypropane (CPP), and dodecanedioic acid (DD). Drug release was affected by polymer composition, physical properties of the microspheres, and type of drug. The potential for injectable microspheres (size range 1-300 jum) made of CPP-SA (50 50) for the controlled release of insulin was assessed. Both 5% and 10% w/w insulin loaded microspheres were prepared. The best clinical response was produced by 10% loaded microspheres, which... 

PROPERTIES OF SPECIAL INTEREST Anhydride Copolymers of 1,3-bis-p-carboxyphenoxypropane (CPP) with aliphatic diacids such as sebacic acid (SA) degrade in a physiological medium to CPP and SA. Matrices of the copolymers loaded with dissolved or dispersed drugs degrade in vitro and in vivo to constantly release the drugs for periods from 1-10 weeks. 

CPPTest The drug-induced CPP test is, in contrast to the IVSA model, a noninvasive and short-lasting method to measure the drug reward and, indirectly, the reinforcing properties of a drug candidate in naive, untrained animals. 

The drug licensing authorities consider the CPP as a valuable but less robust model for testing reinforcing properties of a drug candidate, but it can replace the IVSA paradigm in case of insolubility of the drug candidate (FDA, 2010). 

Besides the CPP test, which is based on the rewarding properties of a drug, a conditioned place aversion (CPA) test is also often described in the literature (Cunningham et al., 2006). In the latter, rats will spend less time in the drug-paired compartment at posttest. A CPA is often related but not limited to drugs that produce aversive effects. Examples hereof described in the literature include naloxone (Cunningham et al., 2006) and lithium chloride (Prus et al., 2009). 

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