Delivery strategies

In conclusion, it should be apparent from this discussion of the absorption mechanisms that, although the major features influencing drug absorption are well known, implementation of a coherent delivery strategy is highly specific for any compound, and many variables need to be adjusted for their significant influence on absorption and more importantly, on bioavailability. In addition, from the suggestion of the role of... 

Overall, the prodrug approach is a well-established strategy to improve the bioavailability and targeting of pharmacophores, and is a vital component in the development of therapeutics and drug-delivery strategies. 

Modern Delivery Strategies Physiological Considerations for Orally Administered Medications... 

The volume is divided into five sections. Part one looks at the experimental study of membrane permeability and oral absorption. In Part two, problems of measuring and prediction solubility, as one of the key determinants in the absorption process, will be discussed in detail. In the next part, progress in the science around transporter proteins and gut wall metabolism and their effect on the overall absorption process is presented. Part four looks at the in silico approaches and models to predict permeability, absorption and bioavailability. In the last part of the book, a number of drug development issues will be highlighted, which could have an important impact of the overall delivery strategies for oral pharmaceutical products. 

Lastly, pharmacogenomics could provide new tools for the design of more specific and active CNS pharmaceuticals. The efficacy of a broad spectrum of neuro-pharmaceutical drugs is often complicated by their inability to reach their site of action because of the BBB. One way to overcome this is to use carrier-mediated transport at the luminal and/or abluminal membranes of the endothelial cells of the BBB. This will provide a physiologically based drug delivery strategy for the brain by designing new chemical entities or fused proteins that can cross the BBB via these transporters. 

T. Coviello, P. Matricardi, and F. Alhaique, Drug delivery strategies using polysaccharidic gels, Expert Opin. Drug Deliv., 3 (2006) 395 -04. 

Given such difficulties, it is not unsurprising that bioavailabilities below 1 per cent are often recorded in the context of oral biopharmaceutical drug delivery. Strategies pursued to improve bioavailability include physically protecting the drug via encapsulation and formulation as microemulsions/microparticulates, as well as inclusion of protease inhibitors and permeability... 

Sinko PJ, Lee YH, Makhey V, Leesman GD, Sutyak JP, Yu H, Perry B, Smith CL, Hu P, Wagner EJ, Falzone LM, Mcwhorter LT, Gilligan JP and Stern W (1999) Biopharmaceutical Approaches for Developing and Assessing Oral Peptide Delivery Strategies and Systems In Vitro Permeability and In Vivo Oral Absorption of Salmon Calcitonin (Set). Pharm Res 16 pp 527-533. 

An increasing number of preclinical and clinical studies have been conducted in recent years aiming to clarify the barrier function of the colonic epithelium in more detail and to devise drug delivery strategies, for example, by modulating factors limiting colonic drug absorption. For preclinical... 

Intracellular communication often proceeds in a pulsatile, rhythmic manner [126]. Moreover, an increasing number of hormones are found to be secreted in a pulsatile manner, and the physiological efficiency of these signals appears to be closely related to their frequency [126]. Based on this understanding, a number of classes of drug therapies have been shown to require a periodic, pulsatile regimen of delivery for efficacy or optimization [131], and several delivery strategies have been proposed to respond to this need [127-131]. 

For the correct interpretation of brain uptake studies in general and for the pharmacokinetic validation of a given delivery strategy, it is necessary to be familiar with characteristics and limitations of the applied technique [41]. 7k vivo methods remain the gold standard, as there are still no cell culture models available that fully represent the barrier characteristics. 

An alternative delivery strategy for small molecules is based on the presence of the nutrient transporters. Drugs that are structurally similar to substrates of a carrier system can undergo facilitated brain uptake as pseudoneutrients. The best example of this is the therapeutic use of L-DOPA in Parkinson s disease. Unlike the neurotransmitter dopamine itself, which cannot cross the BBB in significant amounts, its precursor L-DOPA is a substrate for LAT, the transporter of large neutral amino acids [56]. Its uptake by the brain is saturable, and subject to competition by the other substrates of the carrier present in plasma. 

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