Chemical-based delivery system

This approach, known as the chemical-based delivery system (CDS), has been... 

Lipids, unlike many excipients, whether present in food or as discreet pharmaceutical additives, are processed both chemically and physically within the GIT before absorption and transport into the portal blood (or mesenteric lymph). Indeed, most of the effects mediated by formulation-based lipids or the lipid content of food are mediated by means of the products of lipid digestion—molecules that may exhibit very different physicochemical and physiological properties when compared with the initial excipient or food constituent. Therefore, although administered lipids have formulation properties in their own right, many of their effects are mediated by species that are produced after transformation or activation in the GIT. An understanding of the luminal and/or enterocyte-based processing pathways of lipids and lipid systems is therefore critical to the effective design of lipid-based delivery systems. 

Apicella A, Capello B, Del Nobile MA, La Rotonda MI, Mensitieri GL, Nicolais S, Seccia S (1994) Poly(ethylene oxide)-based delivery systems. In Ottenbrite M (ed) Polymeric drugs and drug administration. American Chemical Society, Washington DC... 

A review of micro-electromechanical systems (MEMS)-based delivery systems provides more detailed information of present and future possibilities (52). This covers both micropumps [electrostatic, piezoelectric, thermopneumatic, shape memory alloy bimetallic, and ionic conductive polymer films (ICPF)] and nonmechanical micropumps [magnetohydrodynamic (MHD), electrohydrodynamic (EHD), electroosmotic (EO), chemical, osmotic-type, capillary-type, and bubble-type systems]. The biocompatibility of materials for MEMS fabrication is also covered. The range of technologies available is very large and bodes well for the future. 

Based on the fact that fine-tuning of the physical and chemical properties of silicones is possible and that silicones are considered to be physiologically inert, the development of biocompatible silicone-based delivery systems for bioactive compounds seems a challenging... 

Dmg loading in micro- and nanoparticulate systems is generally carried out by one of two methods, i.e. during the preparation of particles (incorporation) or after their formation (incubation). The dmg delivery properties are also essentially dependent on the chemical and textural properties of the matrices, the porosity, wettability, erosion and the surface area. The matrix equally has an impact on the discharge profile for the bioavailability of the entrapped dmg. Nanoparticle-based delivery systems have the potential power to improve dmg stability, increase the duration of the therapeutic effect and permit enteral or parenteral administration, which may prevent or minimize dmg degradation and metabolism as well as cellular efflux [70, 71]. Protein nanoparticles can conveyance medications transversely across the blood-brain barrier that are not usually passed across after injection. A number of authors have demonstrated a considerable tendency for an accumulation of protein nanoparticles in certain tumours. The binding of a variety of cytotoxic dmgs, such as 5-fluorouracil,... 

A number of factors must be considered when selecting a suitable polysaccharide or combination of polysaccharides to fabricate a biopolymer-based delivery system. It is important to establish suitable environmental and solution conditions in which the polysaccharide molecules can associate with other polysaccharide or non-polysaccharide structure-forming molecules. To do so, one needs to know the physicochemical properties of the polysaccharides involved, such as helix-coil transition temperatures (for carrageenan, alginate,pectin) electrical properties (pKa values) sensitivity to specific monovalent or multivalent ions or susceptibility to enzyme or chemical reactions (BeMiller and Whistler, 1996). The most widely used carbohydrates for encapsulation purposes are probably alginates (Kailasapathy and Champagne, 2011 Kainmani et al, 2011), starch (Li et al, 2009) and its linear biopolymer amylose (Lalush et al, 2005). 

Poly-j3-malate is readily degraded completely to L-malic acid under both acid and base conditions [108], and it can also be hydrolyzed by enzymes within the cell [105,106]. Recently, several bacteria were isolated which were able to utilize poly-/i-malate as sole carbon source for growth [109]. Because the polymer is biodegradable and bioadsorbable, it is of considerable interest for pharmaceutical applications, especially in controlled-release drug delivery systems [97,98]. Chemical routes to poly-/ -malate are expected to provide materials with various properties [110]. 

The oxidation of dihydropyridine-based chemical delivery systems (CDSs) pioneered by Bodor and co-workers [176] has been discussed in a previous book (Chapt. 13 in [81]). There, we examined the principles by which such compounds function to deliver drugs to the brain. Here, we focus our attention to the last step in the activation of these double prodrugs, namely hydrolysis to release the drug. 

Fig. 8.14. Stepwise activation of dihydrotrigonelline-based chemical delivery systems, first by oxidation to a pyridinium cation (Reaction a), and then by hydrolysis to trigonelline and the drug ROH (Reaction b). Direct hydrolysis (Reaction c) is slow in comparison to the Reactions...

Cyclic. S -Mannich bases are rarely encountered in medicinal chemistry. The (R)-thiazolidine-4-carboxylic acids (11.113, Fig. 11.15), which are used as derivatives and chemical delivery systems for L-cysteine (11.114), provide an excellent example of S-Mannich bases. These compounds underwent activation by two distinct mechanisms, directly by nonenzymatic hydrolysis to cysteine and the original aldehyde (Fig. 11.15, Pathway a), and oxidatively (Pathway b) [138]. The latter route involved first oxidation by mitochondrial enzymes to the (f )-4,5-dihydrothiazole-4-carboxylic acid (11.115), followed by (presumably nonenzymatic) hydrolysis to /V-acylcysleine, and, finally, cytosolic hydrolysis to cysteine (11.114). 

Based on an overview of numerous studies, the extent to which Ca and trace mineral interactions occur appears to be related to such factors as the source of Ca, the ratio of Ca in relation to other minerals, the timing of Ca and trace mineral intake, meal interactions, food formulations, and natural food chemical compositions (Smith, 1988). As described in the following sections, CCM has been evaluated for its impact on the absorption of other minerals and, based on the results of these studies, appears to provide a unique delivery system for dietary Ca that does not appreciably affect the availability or status of other minerals. 

Silva et al. (2006) studied starch-based microparticles as a novel strategy for tissue engineering applications. They developed starch-based microparticles, and evaluated them for bioactivity, cytotoxicity, ability to serve as substrates for cell adhesion, as well as their potential to be used as delivery systems either for anti-inflammatory agents or growth factors. Two starch-based materials were used for the development of starch-based particulate systems (1) a blend of starch and polylactic acid (SPLA) (50 50 w/w) and (2) a chemically modifled potato starch, Paselli II (Pa). Both materials enabled the synthesis of particulate systems, both polymer and composite (with BG 45S5). A simple solvent extraction method was employed for the synthesis of SPLA and SPLA/BG microparticles, while for Pa and Pa/BG... 

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