Controlled delivery polymer

Gliadel - a controlled-delivery polymer wafer is the combination of a copolyanhydride matrix consisting of CPP and sebacic acid (20/80 mol. ratio) in which an anticancer agent is physically admixed. Clinical investigations of Gliadel implants in rabbit brains have shown limited toxicity, initial activity and fast excretion of decomposition products as free acids (J4). 

Small molecules can penetrate and penneate tlirough polymers. Because of this property, polymers have found widespread use in separation teclmology, protection coating, and controlled delivery [53]. The key issue in these applications is the selective penneability of the polymer, which is detennined by the diffusivity and the solubility of a given set of low-molecular-weight compounds. The diffusion of a small penetrant occurs as a series of jumps... 

Among other uses, these polymers have been employed in a variety of biomedical applications. Poly(phosphazenes) containing organic side chains, derived from the anaesthetics procaine and benzocaine, have been used to prolong the anaesthetic effect of their precursor drugs. They have also been used as the bioerodable matrix for the controlled delivery of drugs. 

The high permeability of PCL and its copolymers coupled with a controllable induction period prior to polymer weight loss (vide infra) lends itself to the development of delivery devices that are based on diffusion-controlled delivery of the drug during the induction period prior to weight loss. The subsequent biodegradation of the polymer serves the purpose of eliminating the need to recover the spent device. 

The biomedical uses of polyphosphazenes mentioned earlier involve chemistry that could in principle be carried out on a classical petrochemical-based polymer. However, in their bioerosion reactions, polyphosphazenes display a uniqueness that sets them apart. This uniqueness stems from the presence of the inorganic backbone, which in the presence of appropriate side groups is capable of undergoing facile hydrolysis to phosphate and ammonia. Phosphate can be metabolized, and ammonia is excreted. If the side groups released in this process are also metabolizable or excretable, the polymer can be eroded under hydrolytic conditions without the danger of a toxic response. Thus, poljnners of this tjT are candidates for use as erodible biostructural materials or sutures, or as matrices for the controlled delivery of drugs. Four examples will be given to illustrate the opportunities that exist. 

There are many polymers which have been used as physical matrices for controlled delivery of drugs. In this paper, these polymers are separated into water-soluble, biodegradable, and nonbiodegradable materials. A description of each class of polymers is presented. Examples of polymers from each class that have been used as drug delivery matrices and the criteria for their selection are included in this general review. 

Control elements, final, 20 684-687 Controlled atmosphere storage (CAS), of food products, 12 77 21 564-565 Controlled delivery devices, biocompatibility of, 9 56 Controlled depletion polymer antifouling coatings, 7 158... 

S. Luo and D. R. Walt, Fiber-optic sensors based on reagent delivery with controlled-release polymers. Anal. Chem, 61, 174-177 (1989). 

Lee, Y.L., and Chien, Y.W., Oral mucosa controlled delivery of LHRH by bilayer mucoadhesive polymer systems, J. Control. Rel., 37 251-261 (1995). 

SIP-driven polymer brush library fabrication leverages the fact that the polymerization initiation species are permanently bound to the substrate. Since the initiators are tethered, controlled delivery of monomer solution to different areas of the substrate results in a grafted polymer library. In NIST work, initiators bound via chlorosilane SAMs to silicon substrates were suitable for conducting controlled atom transfer radical polymerization (ATRP) [53] and traditional UV free radical polymerization [54, 55]. Suitable monomers are delivered in solution to the surface via microfluidic channels, which enables control over both the monomer solution composition and the time in which the solution is in contact with the initiating groups. After the polymerization is complete, the microchannel is removed from the substrate (or vice versa). This fabrication scheme, termed microchannel confined SIP ([t-SIP), is shown in Fig. 10. In these illustrations, and in the examples discussed below, the microchannels above the substrate are approximately 1 cm wide, 5 cm long, and 300-500 [tm high. 

A host of bioadhesive controlled release systems have been proposed in recent years. Among the most commonly studied applications of bioadhesive materials is the area of buccal controlled delivery [408], The buccal delivery of small peptides from bioadhesive polymers was studied by Bodde and coworkers [409], and a wide range of compositions based on poly(butyl acrylate) and/or poly(acrylic acid) gave satisfactory performance. Bioadhesive poly(acrylic add)-based formulations have also been used for oral applications [402,410] for the sustained delivery of chlorothiazide [410] and for a thin bioadhesive patch for treatment of gingivitis and periodontal disease [411]. Other bioadhesive applications of polyelectrolytes include materials for ophthalmic vehicles [412,413], and systems for oral [410,414,415-419], rectal [420,421] vaginal [422] and nasal [423] drug delivery. 

The possibility of controlling the morphology of the product is relevant, especially in the forms of bio-polymer preparations and controlled delivery systems. Polymeric microparticles, fibers, or three-dimensional networks can be produced by tuning the operating variables. 

A. Zaffaroni, Applications of Polymers in Rate-controlled Drag Delivery, Polym. Sci. Tech. 14, 293 (1981). 

H. Ghandehari, P. Kopecekova, P. Y. Yeh, H. Ellens, P. L. Smith, and J. Kopecek, Oral colon-specific protein and peptide delivery Polymer system and permeability characteristics, Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 23 59-60... 

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