Particulate delivery systems

A variety of methods have been reported for producing microspheres including phase separation by polymer/polymer incompatibility and coacerva-tion [81] solvent evaporation or solvent removal [82] hot-melt microencapsulation spray drying interfacial polymerization and supercritical fluidprocessing teehniques (such as the gas antisolvent spray precipitation process [83] or rapid expansion of supercritical fluids [84]). The characteristics of the most important of these methods have been reviewed [85, 86]. 

In other applications, different patterns of release are desirable. Micropartiele vaccines are often designed to mimic a pattern of vaccine boosts that elicits optimal immunity. This approach has been tested for HIV vaceines based on recombinant gpl20 [89]. A malaria vaccine has been 

Solid Polymer with Dispersed or Dissolved Drug 

Liposomes can also be considered particulate dehvery systems, but in this text they are considered together with drug-modification methods in Chapter 8. 

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The most potent mucosal adjuvants have been shown to be the toxins derived from Vibrio cholerae or Escherichia coli, which should not be surprising since these organisms invade the body through the GI tract. Obviously too toxic for human use because they are the source of cholera or diarrhoea, heat labile enterotoxins have been tested in mice and shown to be potent adjuvants for orally or nasally administered influenza vaccine. The potency of heat-labile enterotoxin mutants may also be enhanced by formulation into bioadhesive particulate delivery systems, and this is an area under current exploration. 

Amphiphilic poly(ethylene glycol)-alkyl dextran ethers are emerging as vehicles in the oral delivery of poorly water soluble drugs [251,268,269]. They form polymer micelles of low critical association concentrations (CAC) and small micelle sizes in aqueous solution. Particulate delivery systems lead to an enhancement of the absorption efficiency and bioavailability of highly hpophihc drugs orally applied, and provide the drug with some level of pro-... 

Bramwell VW, Perrie Y (2005), Particulate delivery systems for vaccines,... 

The process of phagocytosis is of particular relevance when particulate delivery systems, such as microspheres, liposomes and other advanced delivery systems (described in Chapter 5), are used. Such particulate carriers are susceptible to MPS clearance. Sequestration by the MPS is useful in some cases, for example in the treatment of certain microbial diseases. However, if the drag is to be delivered to sites other than the MPS, it is highly undesirable. Therefore considerable research effort is being directed towards methods of avoiding MPS uptake of drag delivery systems. Strategies to both exploit and avoid MPS uptake are described in detail in Chapter 5 (see Section 5.1.4). 

Nanoparticles Nanoparticles have been among the most widely studied particulate delivery systems over the past three decades. They are defined as submicrometer-sized polymeric colloidal particles ranging from 10 to 1000 nm in which the drug can be dissolved, entrapped, encapsulated, or adsorbed [206]. Depending on the preparation process, nanospheres or nanocapsules can be obtained. Nanospheres have a matrixlike structure where the drug can either be firmly adsorbed at the surface of the particle or be dispersed/dissolved in the matrix. Nanocapsules, on the other hand, consist of a polymer shell and a core, where the drug can either be dissolved in the inner core or be adsorbed onto the surface [207],... 

Buchanan. John S., and Schoennagel, Hans J. Laboratory fluid catalytic cracking riser and particulate delivery system, PATENT United States US 4978441 A, Date 901218 (1990). 

Figure 9.24 Particles for drug delivery. Particulate delivery systems include (a) microcapsules, (b) microparticles, and (c) surface-modified nanoparticles. In the nanoparticles, the drug is entrapped in the solid pol)mier core.

Bramwell, V.W. and Petrie, Y. 2006. Particulate delivery systems for vaccines What can we expect J. Pharm. Pharmacol. 58 717-728. 

The vehicle format we have used to produce aquasomes is the complex particulate multicomponent system. In general, complex particulate delivery systems are assemblies of simple polymers, complex lipid mixtures or ceramic materials that tend to measure individually between 30 and 500 nm in diameter. Being solid or glassy particles dispersed in an aqueous environment, they exhibit the physical properties of colloids their mechanism of action is controlled by their surface chemistry. They may deliver agents through a combination of specific targeting, molecular shielding, and slow release processes. 

For non-invasive drug administration, particulate delivery systems offer the advantage of providing a prolonged residence time oti mucosal membranes [65] and the possibility to reach greater mucosal surface areas, leading to a comparatively higher... 

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