Bioerodible poly

Poly(orthoesters) represent the first class of bioerodible polymers designed specifically for dmg deUvery appHcations (52). In vivo degradation of the polyorthoester shown, known as the Al amer degradation, yields 1,4-cydohexanedimethanol and 4-hydroxybutyric acid as hydrolysis products (53). 

Poly(anhydrides). Poly(anhydrides) are another class of synthetic polymers used for bioerodible matrix, dmg dehvery implant experiments. 

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 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. 

A recent development has been the synthesis of bioerodible poly-phosphazenes that bear glyceryl side groups (35). The synthesis of these polymers requires a protection-deprotection sequence to reduce the functionality of the glycerol and prevent crosslinking. 

Hydrogels, 13 729-759. See also Microgels Superabsorbent polymers (SAPs) AMPS polymer, 23 721 applications for, 13 747-753 biodegradable, 13 739-742 bioerodible, 9 63 conducting, 7 524 cross-linked poly (ethylene oxide),... 

Some of the most useful polyphosphazenes are fluoroalkoxy derivatives and amorphous copolymers (11.27) that are practicable as flame-retardant, hydrocarbon solvent- and oil-resistant elastomers, which have found aerospace and automotive applications. Polymers such as the amorphous comb polymer poly[bis(methoxyethoxyethoxy)phosphazene] (11.28) weakly coordinate Li " ions and are of substantial interest as components of polymeric electrolytes in battery technology. Polyphosphazenes are also of interest as biomedical materials and bioinert, bioactive, membrane-forming and bioerodable materials and hydrogels have been prepared. 

Alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) are bioerodible acidic polymers that are used to control drug release. In biological fluids with poor buffering capacity, drug release from the polymers and their dissolution are slowed owing to the lower pH on the polymer surface. We studied whether the release of timolol from matrices of monoisopropyl ester of PVM-MA in vitro and in vivo in rabbits eyes could be affected by disodium phosphate in the matrices. Addition of disodium phosphate to the matrices doubled the release rate of timolol in vitro, but it did not affect the bulk pH of the dissolution medium. On the basis of the timolol concentrations in the tear fluid and in systemic circulation, disodium phosphate seems to accelerate drug release in vivo also. Disodium phosphate probably affects the rate of dmg release by increasing the microenvironmental pH on the polymer surface. 

Bioerodible alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) (Fig. 1) can be used to control drug release. Being acidic, ionizable polymers the pH of the disolution medium affects the rate of polymer dissolution [1]. 

Varshney et al. (3) prepared biocompatible and bioerodable poly(lactide-co-succinic anhydride) derivatives having a Young s modulus between about 1.5 and 3, which had enhanced surface degradation rates. 

The main class of bioerodible polyphosphazenes that have been developed so far are polymers with amino acid ester side groups. They are prepared by the reaction of poly(dichlorophosphazene) with the ethyl or propyl esters of amino acids such as glycine, alanine, phenylalanine, and so on (reaction (57)).196 The ethyl or propyl ester of the amino acid must be used as the nucleophile in this reaction for two reasons. First, a free carboxylic acid unit would provide a second nucleophilic site that could lead to... 

As pointed out by Heller (2), polymer erosion can be controlled by the following three types of mechanisms (1) water-soluble polymers insolubilized by hydrolytically unstable cross-links (2) water-insoluble polymers solubilized by hydrolysis, ionization, or protonation of pendant groups (3) hydrophobic polymers solubilized by backbone cleavage to small water soluble molecules. These mechanisms represent extreme cases the actual erosion may occur by a combination of mechanisms. In addition to poly (lactic acid), poly (glycolic acid), and lactic/glycolic acid copolymers, other commonly used bioerodible/biodegradable polymers include polyorthoesters, polycaprolactone, polyaminoacids, polyanhydrides, and half esters of methyl vinyl ether-maleic anhydride copolymers (3). 

Toxic degradation products this effect is applicable to biodegradable polymers for example, degradation of poly(alkylcyanoacrylate) leads to the formation of formaldehyde which is considered toxic in humans. In the case of a bioerodible polyvinylpyrrolidone), the accumulation of the dissolved polymer in the liver raises a longterm toxicity issue. 

Polyethylene oxide)—poly(/-lacride)b block copolymer biodegradable/bioerodible... 

Title Bioerodible Poly (Ortho Esters) from Dioxane-Based Di(Ketene Acetals) and Block Copolymers Containing Them... 

Bioerodible poly(ortho ester) copolymers containing hydrophilic and hydrophobic blocks have been prepared from di(ketene acetals) and oligomeric diols. These materials form micelles in aqueous solution making them useful as hydrophobic encapsulation agents or as bioerodible matrices for the sustained release of medicaments. 

TABLE 1. Selected poly(ortho ester) copolymers having bioerodible matrices used for the sustained release of medicaments. 

The feedback-regulated drug delivery concept has been applied to the development of a bioerosion-regulated CrDDS by Heller and Trescony. " This CrDDS consists of a drug-dispersed bioerodible matrix fabricated from poly(vinyl methyl ether) half-ester, which was coated with a layer of immobilized urease (Fig. 26). In a solution with near neutral pH, the polymer only erodes very slowly. In the presence of urea, urease at... 

Cho, C.S. Han, S.Y. Ha, J.H. Kim, S.H. Lim, D.Y. Clonazepam release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(epsilon-caprolactone) and poly(ethylene glycol) macromer. Int. J. Pharm. 1999, 181, 235-242. 

Poly(e-caprolactone) PEG Bioerodible drug release Kim etal., 1995... 

Bioerodible polymers offer a unique combination of properties that can be tailored to suit nearly any controlled drug delivery application. By far the most common bioerodible polymers employed for biomedical applications are polyesters and polyethers (e.g., poly(ethylene glycol), polylactide, polyglycolide and their copolymers). These polymers are biocompatible, have good mechanical properties, and have been used in... 

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