May 2010 Vol 10 No 4 Drugdeliverytech IN THIS ISSUE

the latter’ssensitivity to moisture.

20-25-DDT May 2010- Controlled Release:Layout 1 4/30/10 2:40 PM Page 23FIGURE 3Degradation of polyester urethanes showing reduced pH drop compared to analogous non-lysinebearing hydroxyester-based microspheres, and the varying degradation rates obtained by varying thehydroxyester backbone.mechanical properties, polarity, orparticular diffusion characteristics of thepolymer. This has led to the incorporationof biological building blocks indegradable polymers for medicalapplications. Most notably has been theincorporation of amino acid-basedbuilding blocks. Amino acids offer morethan being biodegradable andmetabolizable building blocks; they maymoreover provide one or more reactivesites that allow further modification of thepolymer to tailor physicochemicalproperties, tune cellular response, or serveas a handle for the chemical attachmentof functional molecules, including drugs.Initial development on amino acidbased polyamidoamines was complicatedby their poor solubility and processabilityas well as their low level systemic toxicityupon degradation. To address theselimitations, amino acid-based polyesterurethanes, polyester amides, andpolycarbonates were developed.POLYESTERURETHANESThe incorporation of amino acids inpolyurethanes originally stemmed fromobservations that supposedly biostablepolyurethanes were in fact degraded dueto inflammation-derived enzymaticactivity, thus generating non-natural andoften toxic amine-functional degradationproducts. The isocyanates used to producethe polyurethanes resulted in non-naturalamine degradation products and triggeredthe development of isocyanates thatgenerated natural amine-baseddegradation by-products. These were mostnotably the use of butanediisocyanate andFIGURE 4AMINO ACID-BASEDBIODEGRADABLE POLYMERSWith degradation comes the releaseof degradation products into the body, thetoxicity of which should be taken intoaccount when selecting building blocksused to synthesize a degradable polymer.The nature of the resultant degradationby-products is as important as selectingbuilding blocks for achieving desiredA new generation of amino acid-based biodegradable polyesteramides for drug delivery and othermedical applications.Drug Delivery Technology May 2010 Vol 10 No 4Thus, in the design of degradablepolymer-based drug delivery systems, it isworthwhile evaluating both chemicallydegradable and enzymaticallybiodegradable polymers and scrutinize thein vitro and in vivo testing results todefine the optimal system of which toproceed.Polylactic acid (PLA) andcopolymers with glycolic acid (PLGA)have been the most widely used materialsfor drug delivery. PLA- and PLGA-basedsystems are used as matrix reservoirs inwhich drug is dispersed within thepolymer materials and is released both bydiffusion through the polymer and as thepolymer degrades.Whereas these systems havesuccessfully demonstrated the ability todeliver drugs in a controlled manner overprolonged periods of time, they areassociated with significant limitations forfurther expansion of their use, related toitems such as acidic degradation products,the relative hydrophobicity, etc.The follwing presents the nextevolution in biodegradable materials thatare prepared via synthetic incorporationof amino acid building blocks. Theincorporation of amino acid buildingblocks provides not only a naturaldegradation end product but thepossibility to address the limitations ofthe conventional degradable polymers.A thermoset degradable polymer(polyesterurethane) and a thermoplasticpolyester amide both bearing amino acidbuilding blocks and their degradationcharacteristics are described.23

20-25-DDT May 2010- Controlled Release:Layout 1 4/30/10 2:40 PM Page 24FIGURE 5Drug Delivery Technology May 2010 Vol 10 No 4In vitro paclitaxel release profiles from cross-linked phenylalanine-based polyesteramide hydrogelsin pure PBS buffer and in an alpha-chymotrypsin solution at 37oC.524lysine diisocyanate

pros and cons of hydrolytically degradable versus enzymatically or biodegradable polymers. It has been speculated that polymers that degrade via . 20-25-DDT May 2010- Controlled Release:Layout 1 4/30/10 2:40 PM Page 23. D r u g D e l i v e