Drug polymeric micelles

Chapter 5 - Aiming to gain further insight into the complexity of drug/polymeric micelle interaction phenomena, the present chapter investigated the incorporation of the poorly water-... 

Aiming to gain further insight into the complexity of drug/polymeric micelle interaction phenomena, the present chapter investigated the incorporation of the poorly water-soluble topical antibacterial agent triclocarban (TCC) into polymeric micelles of the branched pH/temperature-responsive poly(ethylene oxide)-poly(propylene oxide) block copolymers Tetronic 1107 (MW = 15 kDa, 70 wt% PEG) and 1307 (MW = 15 kDa, 70 wt% PEG). Solubility extents showed a sharp increase of up to 4 orders of magnitude. Due to the pH-... 

A large variety of drug delivery systems are described in the literature, such as liposomes (Torchilin, 2006), micro and nanoparticles (Kumar, 2000), polymeric micelles (Torchilin, 2006), nanocrystals (Muller et al., 2011), among others. Microparticles are usually classified as microcapsules or microspheres (Figure 8). Microspheres are matrix spherical microparticles where the drug may be located on the surface or dissolved into the matrix. Microcapsules are characterized as spherical particles more than Ipm containing a core substance (aqueous or lipid), normally lipid, and are used to deliver poor soluble molecules... 

Fig. 30 Types of nanocarriers for drug delivery, (a) Polymeric nanoparticles polymeric nanoparticles in which drugs are conjugated to or encapsulated in polymers, (b) Polymeric micelles amphiphilic block copolymers that form nanosized core-shell structures in aqueous solution. The hydrophobic core region serves as a reservoir for hydrophobic drugs, whereas hydrophilic shell region stabilizes the hydrophobic core and renders the polymer water-soluble.

The copolymer-based systems possessing the core-shell structure in solutions are known and studied rather well (see, e.g., [14-16]). These copolymers in aqueous media tend to form polymeric micelles, which are often considered as promising drug delivery nano-vehicles [ 17,18], i.e., these macromolecular systems are not only of scientific, but also of considerable applied significance. Among such systems there are interesting examples, whose properties are very similar to the properties that should be inherent in the protein-like copolymers. All of these macromolecules possess the primary structure of... 

Thermoresponsive Polymeric Micelles for Double Targeted Drug Delivery... 

ON-OFF SWITCHABLE DRUG RELEASE FROM THERMORESPONSIVE POLYMERIC MICELLES... 

Thermoresponsive polymeric micelles with PIPAAm block copolymers can be expected to combine passive spatial targeting specificity with a stimuli-responsive targeting mechanism. We have developed LCSTs of PIPAAm chains with preservation of the thermoresponsive properties such as a phase transition rate by copolymerization with hydrophobic or hydrophilic comonomers into PIPAAm main chains. Micellar outer shell chains with the LCSTs adjusted between body temperature and hyperthermic temperature can play a dual role in micelle stabilization at a body temperature due to their hydrophilicity and initiation of drug release by hyperthermia resulting from outer shell structural deformation. Simultaneously, micelle interactions with cells could be enhanced at heated sites due... 

Scheme 4 Drug action mechanisms of thermoresponsive polymeric micelles.

Chung, J. E., Yokoyama, M., Yamato, M., Aoyagi, T., Sakurai Y., and Okano, T. Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(A-isopropylacrylamide) and poly(butylmethacrylate), J. Contr. Rel, 1999, 62, 115-127. 

Polymeric micelles are mostly small (10-100 nm) in size and dmgs can be incorporated by chemical conjugation or physical entrapment. For efficient delivery activity, they shonld maintain their integrity for a sufficient amount of time after injection into the body. Most of the experience with polymeric micelles has been obtained in the field of passive targeting of anticancer drugs to tumours [33]. Attachment of antibodies or sugars, or introduction of a polymer sensitive to variation in temperature or pH has also been stndied [32]. 

Chung JE, Yokoyama M, Okano T. Inner core segment design for drug delivery control of thermo-responsive polymeric micelles. J Controlled Release 2000 65 93-103. 

Polymeric oxazolines have also been used as vehicles for controlled drug release ° ° and DNA transfection, as polymeric micelles, which serve as carriers for drug transport (e.g., paclitaxel), and as formulation additives for controlled-release of insecticides. ... 

Kwon GS. Polymeric micelles for delivery of poorly water-soluble compounds. Crit Rev Ther Drug Carrier Syst 2003 20(5) 357-403. 

Formulation of Insoluble Compounds, Liposomes in Solubilization, Micellization and Drug Solubility Enhancement, and Polymeric Micelles in V Mer-lnsoluble Drug Delivery. ... 

In many cases in drug development, the solubility of some leads is extremely low. Fast dissolution rate of many drug delivery systems, for example, particle size reduction, may not be translated into good Gl absorption. The oral absorption of these molecules is usually limited by solubility (VWIImann et al., 2004). In the case of solubility limited absorption, creating supersaturation in the Gl Luids for this type of insoluble drugs is very critical as supersaturation may provide great improvement of oral absorption (Tanno et al., 2004 Shanker, 2005). The techniques to create the so-called supersaturation in the Gl Luids may include microemulsions, emulsions, liposomes, complexations, polymeric micelles, and conventional micelles, which can be found in some chapters in the book. 

Francis, M. F., M. Cristea, and F. M. Winnik (2004). Polymeric micelles for oral drug delivery Why and how. Pure Appl. Chem., 76 1321-1335. 

Florence (1983) provide a comprehensive reference for the use of surfactants in drug formulation development. The treatment by Florence (1981) of drug solubilization in surfactant systems is more focused on the question at hand and provides a clear description of surfactant behavior and solubilization in conventional hydrocarbon-based surfactants, especially nonionic surfactants. This chapter will discuss the conventional surfactant micelles in general as well as update the reader on recent practical/commercial solubilization applications utilizing surfactants. Other uses of surfactants as wetting agents, emulsiLers, and surface modiLers, and for other pharmaceutical applications are nc emphasized. Readers can refer to other chapters in this book for details on these uses of surfactant Polymeric surfactant micelles will be discussed in Chapter 13, Micellization and Drug Solubility Enhancement Part II Polymeric Micelles. 

Micellization and Drug Solubility Enhancement Part II Polymeric Micelles... 

Comparison of Polymeric Micelles with Other Colloidal Drug Carriers. 334... 

As compared with other types of carrier systems, the polymeric micelle systems possess several beneLts (Yokoyama, 1992, 1994) including the wide applicability of polymeric micelle systems to drugs, through either chemical conjugation or physical entrapment and the small size of polymeric micelles. In the case of physical entrapment, utilizing hydrophobic interactions can be applied to many kinds of drugs (Kwon et al., 1994) because most drugs contain hydrophobic moiety(ies) in their chemical structures. 

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