Copolymers drug delivery

VPGEG(IPGAG)4]i4-[VPGFG(IPGVG)4]i4 ELP (Block Copolymer) Drug Delivery [93]... 

Ranquin A, Versees W, Meier W, Steyaert J, Van Gelder P. Therapeutic nanoreactors combining chemistry and biology in a novel triblock copolymer drug delivery system. Nano Lett 2005 5(ll) 2220-4. 

Ranade, S.V., Richard, R.E., and Hehnus, M.N. Styrenic block copolymers for biomaterial and drug delivery applications, Acta Biomater., 1, 137, 2005. 

Poly[(4-carboxylatophenoxy)(methoxyethoxyethoxy)phosphazene] copolymers of variable compositions were synthesized by Allcock [645] in 1996. These polymers were found to be soluble in alkaline solutions. When crosslinked (by y-rays or by addition of CaCl2 to the polymer solution) the resulting hydrogels were found able to contract or expand as a function of the pH of the solution and their utilization as pH-responsive materials for drug delivery systems could be envisaged. 

This review of PCL and its copolymers is largely drawn from the nonpatent literature and focuses primarily on aspects relevant to drug delivery. Methods of polymerization are considered at some length because of the impact on polymer structure and morphology, which in turn determine the permeability and biodegradability of the product. 

Pitt, C. G., Jeffcoat, A. R., Zweidinger, R. A., and Schindler, A., Sustained drug delivery systems. I. The permeability of poly(e-caprolactone), poly(DL-lactic acid), and their copolymers, J. Biomed. Mater. Res., 13. 497-507, 1979. 

ELP-based triblock copolypeptides have also been used to produce stimulus-responsive micelles, and Chaikof and coworkers envisioned the possible application of these micelles as controlled drug delivery vehicles. These amphiphilic triblock copolymers were constructed from two identical hydrophobic ELP endblocks and a hydrophilic ELP midblock. Below the transition temperature, loose and monodispersed micelles were formed that reversibly contracted upon heating, leading to more compact micelles with a reduced size [90]. 

Polymers and copolymers are among the most beneficial materials produced by synthetic chemistry. The invention and commercialization of new polymeric materials with radical new properties provides an opportunity to monopolize the market and justify the expense involved in the research and development. The commercialization of new polymers or copolymers always presents scale-up and design challenges. Scientists have recently developed new polymeric materials whose commercial impact has yet to be realized. Examples are semiconductive and conductive polymers and amphiphilic dendritic block copolymers. Other promising materials, such as polymers for (targeted) drug delivery and... 

Aliphatic polyesters based on monomers other than a-hydroxyalkanoic acids have also been developed and evaluated as drug delivery matrices. These include the polyhydroxybutyrate and polyhydroxy valerate homo- and copolymers developed by Imperial Chemical Industries (ICI) from a fermentation process and the polycaprolactones extensively studied by Pitt and Schindler (14,15). The homopolymers in these series of aliphatic polyesters are hydrophobic and crystalline in structure. Because of these properties, these polyesters normally have long degradation times in vivo of 1-2 years. However, the use of copolymers and in the case of polycaprolactone even polymer blends have led to materials with useful degradation times as a result of changes in the crystallinity and hydrophobicity of these polymers. An even larger family of polymers based upon hydroxyaliphatic acids has recently been prepared by bacteria fermentation processes, and it is anticipated that some of these materials may be evaluated for drug delivery as soon as they become commercially available. 

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. 

Drug Release from PHEMA-l-PIB Networks. Amphiphilic networks due to their distinct microphase separated hydrophobic-hydrophilic domain structure posses potential for biomedical applications. Similar microphase separated materials such as poly(HEMA- -styrene-6-HEMA), poly(HEMA-6-dimethylsiloxane- -HEMA), and poly(HEMA-6-butadiene- -HEMA) triblock copolymers have demonstrated better antithromogenic properties to any of the respective homopolymers (5-S). Amphiphilic networks are speculated to demonstrate better biocompatibility than either PIB or PHEMA because of their hydrophilic-hydrophobic microdomain structure. These unique structures may also be useful as swellable drug delivery matrices for both hydrophilic and lipophilic drugs due to their amphiphilic nature. Preliminary experiments with theophylline as a model for a water soluble drug were conducted to determine the release characteristics of the system. Experiments with lipophilic drugs are the subject of ongoing research. 

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