Effect release kinetics

Whether in copolymers or blends, inhomogeneous erosion has a nontrivial effect on drug release kinetics as will be shown later. Leong et al. (1985) demonstrated that the pH of the degradation media also has a dramatic effect on the erosion rate, which increases with increasing pH. The acceleration of degradation of polyanhydrides with increase in pH is widely reported and has been used to speed up experiments (Shakesheff et al., 1994). 

NO acts as an autocrine factor that mediates HIV-1 replication as at the molecular level, NO seems to stimulate long-terminal repeat-mediated transcription [125]. It was noted that exogenous NO increases replication of HIV-1 T-tropic isolates in primary T cells or T-cell lines, and inhibitors of iNOS partly block HIV-1 replication, especially that induced by tumor necrosis factor a [125]. The contrasting effects of exogenous NO, particularly NO donors, may depend on the type of NO donors, their releasing kinetics, and the dose used in the study design. 

Hvistendahl, G. Uggerad, E. Secondary Isotope Effect on Kinetic Energy Release and Reaction Symmetry. Org. Mass Spectrom. 1985,20,541-542. 

The present study was undertaken to investigate the effect of physicochemical properties of wall-forming materials on the drug release kinetics and bioavailability of microcapsules and micromatrices. The effect of a coacervation-inducing agent on the drug release profile was also studied. 

In connection with the substituent effects, the kinetic stability of benzyne is suggested to be increased by electron withdrawal (-/) and decreased by electron release (+/).73 However, the inference cannot be extrapolated to selectivity of substituted arynes in general. For example, in additions involving competition between phenyllithium and lithium piperidide, the methyl substituents (+/) on benzyne increase its selectivity, whereas methoxy groups (-/) decrease it (Scheme 6). On the other hand, in reactions of car-banions derived from acetonitrile in alkylamine solvents both +/ and -/ benzyne substituents lower selectivity and cause predominant amination. Thus, the method was found unsuitable for preparation of many substituted benzyl nitriles.74 In symmetrically disubstituted arynes there is partial cancellation of polarization, and in fact acceptable yields of acetonitrile adducts could be obtained from 3,6-dimethoxy-benzyne.75 The selectivity of substituted arynes varies with the set of nucleophiles in the competition and no comprehensive theory or simple generalization is available on this point. 

Anderson, M., and A. Omri. 2004. The effect of different lipid components on the in vitro stability and release kinetics of liposome formulations. Drug Deliv 11 33. 

This reaction was followed by a second slower reaction that was not characterized in the report. An analysis of the overall results showed that the influence of steric or electrostatic effects on kinetic parameters is not necessarily minor. The dynamics of binding of NO to the diaqua species is mainly tuned by modulation of electron density on the iron center by the porphyrin macrocycle. A volume profile for NO binding based on values ofAV on and A V 0ff of + 1.5 and + 9.3 cm3/mol, respectively, maybe interpreted as an interchange mechanism for the on reaction, as the Fenl-H20 bond is decidedly stabilized (see Figure 7.15a). The volume of activation for the off reaction indicates a less dissociative mode of activation compared with NO release from other porphyrins. 

The simplest answer is ease of administration. More importantly, there are several limitations to local delivery of drugs in the form of DES. The efficacy of these new devices depends on several variables, including the selection of an effective drug, its solubility, diffusion characteristics, release kinetics, arterial tissue concentration, retention, and whether the platform is polymer based or nonpolymeric. Local delivery of the drug in this manner may delay rather than prevent neointima. This is supported by preclinical studies that show impaired healing and neointimal catch-up (4). There is concern that neointimal growth will accelerate in response to the... 

Serruys PW, Sianos G, Abizaid A, et al. The effect of variable dose and release kinetics on neointimal hyperplasia using a novel paclitaxel-eluting stent platform the Paclitaxel In-Stent Controlled Elution Study (PISCES). J Am Coll Cardiol 2005 46(2) 253-260. 

Overall, key takeaways from the nonpoly meric paclitaxel delivery studies were that despite their improvement of angiographic parameters, paclitaxel-eluting stents without a polymer carrier did not demonstrate a positive effect on clinical outcomes, as seen with polymer-based paclitaxel elution (65), discussed in the next section. Potential reasons for the failure of such an approach could be loss of drug to the systemic circulation prior to reaching the target site during the stent deployment procedure, variability associated with the dose delivered to the lesion, and lack of control over drug-release kinetics due to the absence of a polymer carrier. 

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