Polymeric solubilizing systems

Numerous binary and ternary diene polymerization initiator systems with neodymium as the rare-earth metal component have been designed empirically and investigated since the early discoveries in the 1960s. Commercially used neodymium-based catalysts mostly comprise Nd(III) carboxylates, aluminum alkyl halides, and aluminum alkyls or aluminum alkyl hydrides [43, 48,50-52]. Typically, the carboxylic acids, which are provided as mixtures of isomers from petrochemical plants carry solubilizing aliphatic substituents R. They are treated with the alkylaluminum reagents to generate the active catalysts in situ (Scheme 11). 

They are an attractive medium for polymerization a successful reaction of that kind retaining the structure would mean new and Interesting materials. Claims to such reactions have been made In several Instances from micellar structures to highly solubilized systems (9-13) with varied degree of success. 

Several methods for effective solubilization of drugs into polymer micelles have been developed (Fig. 2). The dialysis method (Fig. 2A) is most widely used for many polymeric micelle systems. The first step involves the dissolution of both polymer and drug in a water-miscible organic solvent such as acetonitrile, acetone, dimethylformamide, or ethanol. Then, the polymer-drug solution is dialyzed against water. As the organic... 

Polymeric micelle systems (PMS) are made by the self-assembly of amphiphilic block copolymers in an aqueous enviromnent. The important features of PMS are drug solubilization, controlled drug release, and drug targeting [26]. This chapter focuses and discusses the current scenario of natural biodegradable polymeric-based nanoblends for protein and gene delivery with a special emphasis on the pharmaceutical and biomedical approaches. 

DLVO theory [1-3] describes the stabilization of colloidal dispersions by an interplay of van der Waals and electrostatic forces (as opposed to steric repulsions of colloids by polymeric solubilizers). The theory was developed in the 1940s by Derjaguin and Landau [4] and by Verwey and Overbeek [5]. In DLVO theory, the two determining interactions for the stability of a colloidal system are the attractive van der Waals interactions between the colloidal particles and the repulsive electrostatic Coulomb interactions. When salt is added, the alteration of the electrostatic interactions affects the stability. 

Similar results have been obtained by Mielke and Ringsdorf [184] when they were studying the spontaneous polymerization of 4-vinylpyridinium perchlorate. Below the CMC a low molecular weight ionene was formed, but above the CMC larger polymers were formed (see Scheme 11.9). Ideally, cross-linked polymerized micellar systems while theoretically capable of solubilizing poorly soluble drugs, would not be subject (as uncross-linked micelles are) to disruption by dilution or addition of solvents which do not favour micelle formation. While attempts at cross-linking micelles of acryloyl derivatives of non-ionic surfactants or poly-... 

Investigation of micelles and solubilized systems as sites for polymerization... 

The kinetic mechanism of emulsion polymerization was developed by Smith and Ewart [10]. The quantitative treatment of this mechanism was made by using Har-kin s Micellar Theory [18,19]. By means of quantitative treatment, the researchers obtained an expression in which the particle number was expressed as a function of emulsifier concentration, initiation, and polymerization rates. This expression was derived for the systems including the monomers with low water solubility and partly solubilized within the micelles formed by emulsifiers having low critical micelle concentration (CMC) values [10]. 

The living nature of ethylene oxide polymerization was anticipated by Flory 3) who conceived its potential for preparation of polymers of uniform size. Unfortunately, this reaction was performed in those days in the presence of alcohols needed for solubilization of the initiators, and their presence led to proton-transfer that deprives this process of its living character. These shortcomings of oxirane polymerization were eliminated later when new soluble initiating systems were discovered. For example, a catalytic system developed by Inoue 4), allowed him to produce truly living poly-oxiranes of narrow molecular weight distribution and to prepare di- and tri-block polymers composed of uniform polyoxirane blocks (e.g. of polyethylene oxide and polypropylene oxide). 

In addition to solubilization, entrapment of polymers inside reversed micelles can be achieved by performing in situ suitable polymerization reactions. This methodology has some specific peculiarities, such as easy control of the polymerization degree and synthesis of a distinct variety of polymeric structures. The size and shape of polymers could be modulated by the appropriate selection of the reversed micellar system and of synthesis conditions [31,191]. This kind of control of polymerization could model and/or mimic some aspects of that occurring in biological systems. 

In a multiphase formulation, such as an oil-in-water emulsion, preservative molecules will distribute themselves in an unstable equilibrium between the bulk aqueous phase and (i) the oil phase by partition, (ii) the surfactant micelles by solubilization, (iii) polymeric suspending agents and other solutes by competitive displacement of water of solvation, (iv) particulate and container surfaces by adsorption and, (v) any microorganisms present. Generally, the overall preservative efficiency can be related to the small proportion of preservative molecules remaining unbound in the bulk aqueous phase, although as this becomes depleted some slow re-equilibration between the components can be anticipated. The loss of neutral molecules into oil and micellar phases may be favoured over ionized species, although considerable variation in distribution is found between different systems. 

Continuous aqueous phase emulsion polymerization is one of the most widely used procedures to make nanoparticles for drug delivery purposes, especially those prepared from the alkylcyanoacrylate monomers. An oil-in-water emulsion system is employed where the monomer is emulsified in a continuous aqueous phase containing soluble initiator and surfactant [39, 40]. Under these conditions, the monomer is partly solubilized in micelles (5-10 nm), emulsified as large... 

Amines such as diethylamine, morpholine, pyridine, and /V, /V, /V, /V -tetramethylethylene-diamine are used to solubilize the metal salt and increase the pH of the reaction system so as to lower the oxidation potential of the phenol reactant. The polymerization does not proceed if one uses an amine that forms an insoluble metal complex. Some copper-amine catalysts are inactivated by hydrolysis via the water formed as a by-product of polymerization. The presence of a desiccant such as anhydrous magnesium sulfate or 4-A molecular sieve in the reaction mixture prevents this inactivation. Polymerization is terminated by sweeping the reaction system with nitrogen and the catalyst is inactivated and removed by using an aqueous chelating agent. 

In vitro enzymatic polymerizations have the potential for processes that are more regio-selective and stereoselective, proceed under more moderate conditions, and are more benign toward the environment than the traditional chemical processes. However, little of this potential has been realized. A major problem is that the reaction rates are slow compared to non-enzymatic processes. Enzymatic polymerizations are limited to moderate temperatures (often no higher than 50-75°C) because enzymes are denaturated and deactivated at higher temperatures. Also, the effective concentrations of enzymes in many systems are low because the enzymes are not soluble. Research efforts to address these factors include enzyme immobilization to increase enzyme stability and activity, solubilization of enzymes by association with a surfactant or covalent bonding with an appropriate compound, and genetic engineering of enzymes to tailor their catalytic activity to specific applications. 

Epoxide polymerizations taking place in the presence of protonic substances such as water or alcohol involve the presence of exchange reactions. Examples of such polymerizations are those initiated by metal alkoxides and hydroxides that require the presence of water or alcohol to produce a homogeneous system by solubilizing the initiator. Such substances increase the polymerization rate not only by solubilizing the initiator but probably also by increasing the concentration of free ions and loose ion pairs. In the presence of alcohol the exchange... 

Extractant leakage from the pores of the polymeric membrane in SLM is due to osmotic flow of massive quantities of water through the membrane. Membrane stability decreases with increasing osmotic pressure gradient and depends upon composition of the SLM system. A high tendency to solubilize water, low extractant/aqueous interfacial tension, and high wettability of polymeric membrane leads to less stable SLMs. The following measures have been proposed for improvement of stability ... 

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