Copolymers in drug delivery

Kabanov AV, Alakhov V. Pluronic block copolymers in drug delivery from micellar nanocontainers to biological response modifiers. Crt Rev Ther Drug Target 2002 19 1-73. 

Details are given of the equilibrium thermorheological properties of oxyethylene-oxypropylene copolymers. The effect of molecular weight, solute and solvent composition on the structural properties was investigated. The efficacy of these copolymers in drug delivery systems is discussed. 32 refs. 

Kabanov V. Alexander and Alakhov Yu Valeri. Pluronie block copolymers in drug delivery From micellar nanoeontainers to biologieal response modifiers. Crit. Rev. Ther. Drug Carr. Syst. 19 no. 1 (2002) 1-72. 

The force-mapping method directly measures the enhancement of the mechanical stability of phase-separated multicomponent lipid bilayers caused by the added PS- -PEO amphiphilic diblock copolymer. In addition, the lipid bilayer-(PS-b-PEO) systems mimic membrane-Pluronic systems and provide a platform for obtaining a fundamental understanding of the role of amphiphilic block copolymers in drug delivery applications as well as being a biological response modifier. 

Ethylene vinyl acetate has also found major applications in drug delivery. These copolymers used in drug release normally contain 30-50 wt% of vinyl acetate. They have been commercialized by the Alza Corporation for the delivery of pilocarpine over a one-week period (Ocusert) and the delivery of progesterone for over one year in the form of an intrauterine device (Progestasert). Ethylene vinyl acetate has also been evaluated for the release of macromolecules such as proteins. The release of proteins form these polymers is by a porous diffusion and the pore structure can be used to control the rate of release (3). Similar nonbiodegradable polymers such as the polyurethanes, polyethylenes, polytetrafluoroethylene and poly(methyl methacrylate) have also been used to deliver a variety of different pharmaceutical agents usually as implants or removal devices. 

Gaucher G, Dufresne MH, Sant VP et al (2005) Block copolymer micelles preparation, characterization and application in drug delivery. J Control Release 109 169-188... 

In the last few years there have been new creative methods of preparation of novel hydrophilic polymers and hydrogels that may represent the future in drug delivery applications. The focus in these studies has been the development of polymeric structures with precise molecular architectures. Stupp et al. (1997) synthesized self-assembled triblock copolymer, nanostructures that may have very promising applications in controlled drug delivery. Novel biodegradable polymers, such as polyrotaxanes, have been developed that have particularly exciting molecular assemblies for drug delivery (Ooya and Yui, 1997). 

EVA copolymer are used in drug delivery systems (30). Drug delivery systems based on matrices of EVA can be manufactured with extrusion technology. Based on this technology, commercially used systems have been developed. 

Shen, E., Pizsczek, R., Dziadul, B., and Narasimhan, B. (2001), Microphase separation in bioerodible copolymers for drug delivery, Biomaterials, 22(3), 201-210. 

Gaucher, G., et al. (2005), Block copolymer micelles Preparation, characterization and apphcation in drug delivery, J. Controlled Release, 109(1-3), 169-188. 

Poly(amino acid)s (PAAs) have also been used in drug delivery PEO-(l-aspartic acid) block copolymer nano-associates , formed by dialysis from a dimethyl acetamide solution against water, could be loaded with vasopressin. PLA-(L-lysine) block copolymer microcapsules loaded with fluorescently labelled (FITC) dextran showed release profiles dependent on amino acid content. In a nice study, poly(glutamate(OMe)-sarcosine) block copolymer particles were surface-grafted with poly(A-isopropyl acrylamide) (PNIPAAm) to produce a thermally responsive delivery system FITC-dextran release was faster below the lower critical solution temperature (LCST) than above it. PAAs are prepared by ring-opening polymerisation of A-carboxyanhydride amino acid derivatives, as shown in Scheme 1. 

Typically, homopolymers are not studied because they possess unfavorable characteristics rendering their handling and manufacture difficult. Poly(SA), poly(CPP), and poly (FA) are semicrystalline and thus suffer from either being brittle or having high Tn,. Conversely, poly(FAD) is a liquid. Therefore, polyanhydrides are often prepared as copolymers of aliphatic and/or aromatic monomers. The most common copolymers under investigation in drug delivery applications include poly(FAD-SA) and poly(CPP-SA). 

Fig. 7 Chemical structures of micelle-forming block copolymers used in drug delivery.

The signiflcant recent advances in both colloidal and polymer chemistries have enabled the successful fabrication of complex, defect-free tianoslruclures following a bottom-up approach [353]. Two recent related examples are mentioned to stress the point. Recently, triblock copolymer with divalent counter-ions in mixed solvents led to the formation of particles with tunable internal structure mimicking lipid anphiphiles for potential use in drug delivery. The mechanism of formation involves either nanophase separation within the triblock copolymer nanoparticle upon addition of water or microemulsion formation similar to that in lipid systems... 

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