Association colloids drugs

Fig. 1 Association colloids (A) spherical micelle (B) cylindrical micelle (C) flattened disc-shaped micelle (D) microtubular micelle (E) inverted micelle and (F) micelle swollen by the presence of solubilized lipid soluble drug.

Polymeric micelles are called the new generation of colloid drug delivery systems [28]. In an aqueous medium, block and random copolymers associate into micelles with a structure similar to that of surfactants. Active substances which are insoluble or poorly soluble in water can be built into the lipophilic part of the micelle in two ways i) with dialysis and ii) with the emulsion method (see Figure 18.4). 

A large number of drugs have been found to exhibit typical colloidal behaviour in aqueous solution in that they accumulate at interfaces, depressing the surface tension, and form aggregates in solution at sufficiently high concentrations. The biological and pharmaceutical implications of this behaviour have been reviewed [1-3] and are discussed later in this chapter. The first part of the chapter will be concerned primarily with the solution properties of the colloidal drugs, with particular emphasis on their mode of association. 

The pure substances would be too irritant, but their action is graded by their slow liberation and by the presence of colloid extractives. The most common of these substances are emodin and chrysophanic acid. Numerous isomers of these are possible (15 for emodin alone). The special character of the different drugs is probably due to differences in these isomers, in the stability of their glucosidal combination, and to the presence of other associated substances (tannin in rhubarb). 

The potential for orally administered drugs to enter the intestinal lymphatics is therefore defined by their selectivity for uptake into the intestinal lymphatics as opposed to the blood capillaries in the subepithelial space. Because selectivity for the lymphatics is primarily defined by size, it is apparent that only macromolecules or colloids will be preferentially absorbed into the intestinal lymphatics. However, the intestine provides a significant barrier to the absorption of both macromolecules and intact colloids, and the most prevalent mechanism for drug delivery to the intestinal lymph is by means of secondary drug association with intestinal lipoproteins [110]. The size of the drug-lipoprotein complex subsequently dictates absorption into the lymphatic vessels. 

Cancer Therapy Nanoparticles were first prepared with the concept of targeting colloidal carriers of nanosize to tumor tissues via the leaky vasculature in tumor regions. Since then nanoparticulate drug carriers have been associated with cancer therapy through passive and active targeting to cancer cells. Thus, amphiphilic CD nanoparticles were mainly focused on cancer therapy and its different aspects. 

Nanoparticles were first developed in the mid-seventies by Birrenbach and Speiser. Later on, their application for the design of drug delivery systems was made available by the use of biodegradable polymers that were considered to be highly suitable for human applications. At that time, the research on colloidal carriers was mainly focusing on liposomes, but no one was able to produce stable lipid vesicles suitable for clinical applications. In some cases, nanoparticles have been shown to be more active than liposomes due to their better stability.This is the reason why in the last decades many drugs (e.g., antibiotics, antiviral and antiparasitic drugs, cytostatics, protein and peptides) were associated to nanoparticles. 

Colloids can be broadly classified as those that are lyophobic (solvent-hating) and those that are lyophilic and hydrophilic. Surfactant molecules, because of their dual affinity for water and oil and their consequent tendency to associate into micelles, form hydrophilic colloidal dispersions in water. Proteins and gums also form lyophilic colloidal systems. Hydrophilic systems are dealt with in Chapters 8 and 11. Water-insoluble drugs in fine dispersion or clays and oily phases will form lyophobic dispersions, the principal subject of this chapter. While lyophilic dispersions (such as phospholipid vesicles and micelles) are inherently stable, lyophobic colloidal dispersions have a tendency to coalesce because they are thermodynamically unstable as a result of their high surface energy. 

Published NMR spectra of diazepam indicate a high mobility of the drug, which indicates a localization of the drug in other colloidal species of high mobility [74] (an association with the solid lipid would cause extensive line broadening [69]). 

Aoyagi T, Sugi K, Sakurai Y, Okano T, Kataoka K. Peptide drug carrier studies on incorporation of vasopressin into nano-associates comprising poly(ethylene glycol)-poly(L-aspartic acid) block copolymer. Colloid Surf B 1999 16 237-242. 

Nanoparticles are solid colloidal polymeric carriers (less than 1 pm in size) that have received much attention over the recent years due to their ability to control dmg release and distribution and due to their biodegradabdity [62]. Furthermore, these systems have proven their potential to administer peptides or other drugs either by intravenous or oral routes, increasing their bioavailability and protection of the dmg against degradation, and reducing the associated adverse effects [63,64]. 

Nanosuspensions consist of the pure poorly water-soluble drug without any matrix material suspended in dispersion. It is sub-micron colloidal dispersion of pure particles of drug stabilized by surfactants. By formulating nanosuspensions, problems associated with the delivery of poorly water-soluble drugs and poorly water-soluble and lipid-soluble drugs can be solved. Nanosuspensions differ from nanoparticles, " which are polymeric colloidal carriers of drugs (nanospheres and nanocapsules), and from solid-lipid nanoparticles, which are lipidic carriers of drug. 

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