Polyanhydrides are a class of
biodegradable polymers characterized by anhydride bonds that connect monomer units of the polymer chain. Their main application is in the medical device and pharmaceutical industry. In vivo, polyanhydrides degrade into non-toxic diacid monomersthat can be metabolized and eliminated from the body. Owing to their safe degradation products, polyanhydrides are considered to be biocompatible.
anhydridebonds in polyanhydrides are water-labile (the polymer chain breaks apart at the anhydride bond). This results in two carboxylic acid groups which are easily metabolizedand biocompatible. Biodegradable polymers, such as polyanhydrides, are capable of releasing physically entrapped or encapsulated drugs by well-defined kinetics and are a growing area of medical research. Polyanhydrides have been investigated as an important material for the short-term release of drugs or bioactiveagents. The rapid degradation and limited mechanical properties of polyanhydrides render them ideal as controlled drug deliverydevices.
One example, Gliadel, is a device in clinical use for the treatment of
brain cancer. This product is made of a polyanhydride wafer containing a chemotherapeutic agent. After removal of a cancerous brain tumor, the wafer is inserted into the brain releasing a chemotherapyagent at a controlled rate proportional to the degradation rate of the polymer. The localized treatment of chemotherapyprotects the immune systemfrom high levels of radiation.
Other applications of polyanhydrides include the use of
unsaturatedpolyanhydrides in bone replacement, as well as polyanhydride copolymers as vehicles for vaccinedelivery.
Classes of Polyanhydrides
There are three main classes of polyanhydrides: aliphatic, unsaturated, and aromatic. These classes are determined by examining their R groups (the chemistry of the molecule between the
anhydridebonds). Aliphaticpolyanhydrides consist of R groups containing carbonatoms bonded in straight or branched chains. This class of polymersis characterized by a crystalline structure, melting temperature range of 50–90 °C, and solubility in chlorinated hydrocarbons. They degradeand are eliminated from the body within weeks of being introduced to the bodily environment. Unsaturatedpolyanhydrides are comprised of organic R groups with one or more double bonds (or degrees of unsaturation). This class of polymershas a highly crystalline structure and is insoluble in common organic solvents. Aromaticpolyanhydrides consist of R groups containing a benzene(aromatic) ring. Properties of this class include a crystalline structure, insolubility in common organic solvents, and melting points greater than 100 °C. They are very hydrophobicand therefore degrade slowly when in the bodily environment. This slow degradationrate makes aromaticpolyanhydrides less suitable for drug delivery when used as homopolymers, but they can be copolymerized with the aliphaticclass to achieve the desired degradation rate.
ynthesis and characterization
Polyanhydrides are synthesized using either melt condensation or solution polymerization. Depending on the synthesis method used,
arious characteristics of polyanhydrides can be altered to achieve the desired product. Characterization of polyanhydrides determines the structure, composition, molecular weight, and thermal properties of the molecule. These properties are determined by using various light-scattering and size-exclusion methods.
Polyanhydrides can be easily prepared by using available, low cost resources. The process can be varied to achieve desirable characteristics. Traditionally, polyanhydrides have been prepared by melt condensation polymerization, which results in high
molecular weightpolymers. Melt condensation polymerization involves reacting dicarboxylic acid monomers with excess acetic anhydride at a high temperature and under a vacuum to form the polymers. Catalystsmay be used to achieve higher molecular weights and shorter reaction times. Generally, a one-step synthesis (method involving only one reaction) is used which does not require purification.
There are many other methods used to synthesize polyanhydrides. Some of the other methods include: microwave heating, high-throughput synthesis (synthesis of polymers in parallel), ring opening polymerization (removal of cyclic monomers), interfacial condensation (high temperature reaction of two monomers), dehydrative coupling agents (removing the water group from two carboxyl groups), and solution polymerization (reacting in a solution).
Chemical structure and composition analysis
chemical structureand composition of polyanhydrides can be determined by H1 NMR spectroscopy. This will determine the class of polanhydride (aromatic, aliphatic, or unsaturated) as well as the structural features of the polymer. For example, the analysis of nuclear magnetic resonance( NMR) peaks allows one to determine if a copolymer has a random or block-like structure. Molecular weightand degradation rate can also determined by NMR.
Molecular weight analysis
Aside from using
NMRto determine a polyanhydride’s molecular weight, gel permeation chromatography(GPC), and viscositymeasurements may also be used.
Differential scanning calorimetry(DSC) is used to determine the thermal properties of polyanhydrides. Glass transition temperature, melting temperature, and heat of fusioncan all be determined by DSC. Crystallinity of a polyanhydride can be determined using DSC, Small angle X-ray scattering (SAXS), Nuclear magnetic resonance(NMR), and X-ray diffraction.
The erosion and degradation of a
polymerdescribe how the polymer physically loses mass ( degrades). The two common erosion mechanisms are surface and bulk erosion. Polyanhydrides are surface eroding polymers. Surface eroding polymers do not allow water to penetrate into the material. They erode layer by layer, like a lollipop. The hydrophobicbackbone with hydrolytically labile anhydride linkages allows hydrolyticdegradation to be controlled by manipulating the polymercomposition. This manipulation can occur by adding a hydrophilicgroup to the polyanhydride to make a copolymer. Polyanhydride copolymers with hydrophilicgroups exhibit bulk eroding characteristics. Bulk eroding polymers take in water like a sponge (throughout the material) and erode inside and on the surface of the polymer.
Drug release from bulk eroding
polymersis difficult to characterize because the primary mode of release from these polymers is diffusion. Unlike surface eroding polymers, bulk eroding polymers show a very weak relationship between the rate of polymer degradation and the rate of drug release. Therefore, the development of surface eroding polyanhydrides incorporated into the bulk eroding polymers is of increased importance.
Biocompatibilityand toxicityof a polymeric material is evaluated by examining systemic toxicresponses, local tissue responses, carcinogenicand mutagenicresponses, and allergicresponses to the material's degradation products. Animal studies are conducted to test the polymer’s effect on each of these negative responses. Polyanhydrides and their degradation products have not been found to cause significant harmful responses and are considered to be biocompatible.
*Domb, A., Amselem, S., Langer, R., and Manair, M. “Chapter 3: Polyanhydrides as Carriers of Drugs.” Biomedical Polymers Designed –to –Degrade Systems. Hanser Publishers: Munich, Vienna, NY, 1994.
*Kumar, N., Langer, R., and Domb, A. “Polyanhydrides: an overview.” Advanced Drug Delivery Reviews, 2002.
*“Polyanhydride Synthesis Techniques.” Wyatt Technology Corp. http://www.lightscattering.com/literature/polyanhydride.pdf
*Tamada, J. and Langer, R. “The development of polyanhydrides for drug delivery applications.” Journal of Biomaterials Science, Polymer Ed. Vol. 3, No. 4, pp. 315–353, 1992.
*Torres, M. P.; Determan, A. S.; Malapragada, S. K.; Narasimhan, B. “Polyanhydrides.” Encyclopedia of Chemical Processing. 2006.
*B.M. Vogel, S.K. Mallapragada, and B. Narasimhan, “Rapid Synthesis of Polyanhydrides By Microwave Polymerization”, Macromolecular Rapid Communications 25, 330-333, 2004.
*B.M. Vogel, S.K. Mallapragada, “Synthesis of Novel Biodegradable Polyanhydrides Containing Aromatic and Glycol Functionality for Tailoring of Hydrophilicity in Controlled Drug Delivery Devices”, Biomaterials, 26, 721-728, 2004.
*B.M. Vogel, Naomi Eidelman, S.K. Mallapragada and B. Narasimhan, “Parallel Synthesis and Dissolution Testing of Polyanhydride Random Copolymers”, Journal of Combinatorial Chemistry, 7, 921-928, 2005.
*B.M. Vogel and S.K. Mallapragada, “The Synthesis of Polyanhydrides”, in Handbook of Biodegradable Materials and their Applications, edited by S.K. Mallapragada and Balaji Narasimhan, ASP Publishers, Vol. 1, 1-19, 2005.
Wikimedia Foundation. 2010.
Look at other dictionaries:
Anhydride d'acide — Un anhydride d acide est un composé organique qui résulte de la déshydratation (perte d une molécule H2O) d un acide organique (acide carboxylique, acide sulfonique, acide phosphorique, etc.) ou inorganique (acide nitrique, acide sulfurique,… … Wikipédia en Français
Biocompatible material — In surgery, a biocompatible material (sometimes shortened to biomaterial) is a synthetic or natural material used to replace part of a living system or to function in intimate contact with living tissue. Biocompatible materials are intended to… … Wikipedia
Polymer — Appearance of real linear polymer chains as recorded using an atomic force microscope on surface under liquid medium. Chain contour length for this polymer is 204 nm; thickness is 0.4 nm. A polymer is a large molecule (macromolecule … Wikipedia
Biodegradable plastic — For information on plastics derived from renewable raw resources (biomass), see Bioplastic. For information on plastics designed to biodegrade in human bodies, see Biodegradable polymer. Utensils made from biodegradable plastic. Biodegradable… … Wikipedia
PAH — or Pah may refer to: In chemistry and biology: Polycyclic aromatic hydrocarbon, one of a class of chemical compounds, organic pollutants Phenylalanine hydroxylase, an enzyme involved in breaking down phenylalanine Para aminohippurate, a substance … Wikipedia
Polymer classes — include:* Biopolymer * Conductive polymer * Copolymer * Fluoropolymer * Gutta percha (Polyterpene) * Inorganic polymer * Phenolic resin * Polyanhydrides * Polyester * Polyolefin (Polyalkene) * Rubber * Silicone * Silicone rubber * Superabsorbent… … Wikipedia
Biomatériau — Les biomatériaux (à ne pas confondre avec écomatériaux) peuvent avoir plusieurs définitions : matériaux produits par certaines biotechnologies, ou plus généralement matériaux biocompatibles avec l organisme humain ou animal, produits en… … Wikipédia en Français
Biomatériaux — Biomatériau Les biomatériaux (à ne pas confondre avec écomatériaux) peuvent avoir plusieurs définitions : matériaux produits par certaines biotechnologies, ou plus généralement matériaux biocompatibles avec l organisme humain ou animal,… … Wikipédia en Français
Classification des polymères — Sommaire 1 Selon leur origine 2 Selon la composition chimique de leur chaîne squelettique 3 Selon leur masse molaire moyenne 4 … Wikipédia en Français