Polymer systems controlled release

HB Rosen, J Kohn, K Leong, R Langer. Bioerodible polymers for controlled release systems. In DST Hsieh, ed. Controlled Release Systems Fabrication Technology, Vol n. Boca Raton, FL CRC Press, 1988, pp 83-110. 

The notion that bioadhesion enhances the efficiency of drug delivery through an intimate and prolonged contact between the delivery device and the absorption site has resulted in considerable efforts to develop and evaluate bioadhesive polymers. The use of bioadhesive polymers in controlled release drug delivery systems provides potential advantages, including... 

Bernkop-Schnurch, A., Scholler, S. and Biebel, R.G. (2000) Development of controlled drug release systems based on thiolated polymers. J. Control. Release 66 39-48. 

Robinson, J. R., and Bologna, W. J. (1994), Vaginal and reproductive system treatments using a bioadhesive polymer, J. Controlled Release, 28,87-94. 

R. J. Linhard, Biodegradable Polymers for Controlled Release of Drugs, in P. Roshoff (ed), Controlled Release of Drugs. Polymers and Aggregate Systems, New York, VCH, 1989. 

Cypes, S. H., Saltzman, W. M., and Giannelis, E. P. 2003. Organosilicate-polymer drug delivery systems controlled release and enhanced mechanical properties. 

Chitosan is a promising polymer for colon delivery because it can be biodegraded by the colonic microflora and it has mucoadhesive character. A thorough study has been carried out on chitosan beads obtained by ionotropic gelation with alginate or tripolyphosphate. The aim was to develop, using natural polymers, a controlled release system that would resist the conditions in the stomach and release its drug... 

S.J. Holland, B.J. Tighe, and P.L Gould, Polymers for biodegradable medical devices. 1. The potential of polyesters as controlled macromolecular release systems, / Controlled Release, 4 (3), 155-180, 1986. 

The ability of a new biodegradable polymer, polyurethane triethylene glycol 1,6-hexa-methylene diisocyanate PU(TEG-HMDI), to act as matrix-forming polymer for controlled release tablets has been studied and its percolation threshold in a matrix system has been estimated [112]. The hydrophilic polyurethane PU(TEG-HMDI) was successfully synthesized by reaction of 1,6-hexamethylene diisocyanate (HMDI) and triethylene glycol (TEG) (Scheme 4.1). The diol monomer (TEG) was chosen to enhance the hydrophilic nature and swelling properties of the new material. These properties contribute to the degradability of the polyurethane. 

Zimmer, A.K., et al. Evaluation of pUocarpine-loaded albumin particles as controlled drug delivery systems for the eye. II. co-administration with taoadhesive and viscous polymers. J. Controlled. Release. 33(1), 31-46 (1995)... 

Phase Separation. Microporous polymer systems consisting of essentially spherical, intercoimected voids, with a narrow range of pore and ceU-size distribution have been produced from a variety of thermoplastic resins by the phase-separation technique (127). If a polyolefin or polystyrene is insoluble in a solvent at low temperature but soluble at high temperatures, the solvent can be used to prepare a microporous polymer. When the solutions, containing 10—70% polymer, are cooled to ambient temperatures, the polymer separates as a second phase. The remaining nonsolvent can then be extracted from the solid material with common organic solvents. These microporous polymers may be useful in microfiltrations or as controlled-release carriers for a variety of chemicals. 

Microcapsules can be used for mammalian cell culture and the controlled release of drugs, vaccines, antibiotics and hormones. To prevent the loss of encapsulated materials, the microcapsules should be coated with another polymer that forms a membrane at the bead surface. The most well-known system is the encapsulation of the alginate beads with poly-L-lysine. 

These discoveries generated a lot of effort over the successive 25 years in the preparation of especially designed drug delivery systems for the controlled release of radioactive progesterone [654], colchicine [656], naproxen [657,673, 674], mitomycin C [675-677], inulin [678], trimethoprin [657], succinylsul-fathiazole [657], ethacrynic acid [653], and steroids [633], regardless of whether these drugs are physically trapped in polyphosphazene matrices, or chemically bonded to the polymer skeleton. 

The concept of fibrous polymer formulations was extended to the delivery of aquatic herbicides (56). Several herbicides including Diquat, Fluridone, and Endothal were spun into biodegradable poly-caprolactone. Monolithic fibers and a modified monolithic system were produced with levels of herbicide from 5 to 60% by weight. Laboratory and field trials showed efficacious delivery of the active agent. Fibers provided both targeted localized delivery and controlled release of the herbicide to the aquatic weed. 

FIGURE 4 Controlled release systems based on lactide/glycolide polymers with duration of action of a few days to 1 year. 

The development of a bioerodible implant capable of releasing controlled amounts of a contraceptive steriod from a subcutaneous implant for periods of time ranging from three months to about a year has been in progress for many years. The three principal bioerodible polymers currently in use are copolymers of lactic and glycolic acid (25), poly(e-caprolactone) (26), and poly (ortho esters) (14). The desire to develop such a contraceptive system was the principal motivation for the initial development of the poly(ortho ester) polymer system. 

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