Design and synthesis of self-degradable antibacterial polymers by simultaneous chain- and step-growth radical copolymerization

Self-degradable antimicrobial copolymers bearing cationic side chains and main-chain ester linkages were synthesized using the simultaneous chain- and step-growth radical polymerization of t-butyl acrylate and 3-butenyl 2-chloropropionate, followed by the transformation of t-butyl groups into primary ammonium salts. We prepared a series of copolymers with different structural features in terms of molecular weight, monomer composition, amine functionality, and side chain structures to examine the effect of polymer properties on their antimicrobial and hemolytic activities. The acrylate copolymers containing primary amine side chains displayed moderate antimicrobial activity against E. coli but were relatively hemolytic. The acrylate copolymer with quaternary ammonium groups and the acrylamide copolymers showed low or no antimicrobial and hemolytic activities. An acrylate copolymer with primary amine side chains degraded to lower molecular weight oligomers with lower antimicrobial activity in aqueous solution. This degradation was due to amidation of the ester groups of the polymer chains by the nucleophilic addition of primary amine groups in the side chains resulting in cleavage of the polymer main chain. The degradation mechanism was studied in detail by model reactions between amine compounds and precursor copolymers.     

Degradation of N5-(2-hydroxyethyl)-L-glutamine and L-glutamic acid homopolymers and copolymers by papain

The rate of degradation of poly[N5-(2-hydroxyethyl)-L-glutamine] (PHEG), poly(L-glutamic acid) (PGA) and poly[HEG-co-GA] random copolymers by papain was measured in the pH range 4.0-7.5, employing the gel permeation chromatography method. The effect of the degree of ionization on the polymer conformation was measured by circular dichroism (c.d.). PHEG, which is uncharged, had a random coil conformation and an almost constant degradation rate within the whole pH interval. The ionization of PGA increased with increasing pH and was accompanied by conformational transition from helix to random coil. The hydrolysis of PGA by papain depended on pH with the optimum at about pH 5, indicating that both the high content of helix (at pH less than 5) and increasing charge density (at pH greater than 5), decreased the degradation rate. Contrary to PGA, pH profiles of the degradation rate of poly[HEG-co-GA] copolymers are monotonous and do not decrease at pH less than 5. In the copolymers the HEG residues act as a helix breaker and limit the formation of helical conformation. The role of structural features of a macromolecular substrate, i.e. the charge, helical conformation and the nature of amino acid residues, in the interaction between enzyme and polymer is discussed.     

Poly(carbonate-ester)s of dihydroxyacetone and lactic acid as potential biomaterials

The synthesis of new polymeric biomaterials using biocompatible building blocks is important for the advancement of the biomedical field. We report the synthesis of statistically random poly(carbonate-ester)s derived from lactic acid and dihydroxyacetone by ring-opening polymerization. The monomer mole feed ratio and initiator concentration were adjusted to create various copolymer ratios and molecular weights. A dimethoxy acetal protecting group was used to stabilize the dihydroxyacetone and was removed using elemental iodine and acetone at reflux to produce the final poly(lactide-co-dihydroxyacetone) copolymers. The characteristics of the copolymers in their protected and deprotected forms were characterized by (1)H NMR, (13)C NMR, GPC, TGA, and DSC. Hydrolytic degradation of the deprotected copolymers was tracked over an 8-week time frame. The results show that faster degradation occurred with increased carbonate content in the copolymer backbone. The degradation pattern of the copolymers was visualized using SEM and revealed a trend toward surface erosion as the primary mode of degradation.     

Pinocytic uptake and intracellular degradation of N-(2-hydroxypropyl)methacrylamide copolymers a potential drug delivery system

Synthetic ¹²⁵I-labelled N-(2-hydroxypropyl)methacrylamide copolymers containing four different, potentially degradable peptidyl side chains were incubated with rat visceral yolk sacs cultured in vitro. All copolymers were captured by fluid-phase pinocytosis and three of the side chains were susceptible to lysosomal hydrolysis, resulting in release of [¹²⁵I]iodotyrosine back into the culture medium. Uptake and degradation was completely inhibited by 2,4-dinitrophenol. The thiol-proteinase inhibitor leupeptin did not affect the rate of pinocytosis, but caused different degrees of inhibition of hydrolysis depending on side chain composition.     

Drug release from and hydrolytic degradation of a poly(ethylene glycol) grafted poly(3-hydroxyoctanoate)

Monoacrylate-poly(ethylene glycol)-grafted poly(3-hydroxyoctanoate) (PEGMA-g-PHO) copolymers were synthesized to develop a swelling-controlled release delivery system for ibuprofen as a model drug. The in vitro hydrolytic degradation of and the drug release from a film made of the PEGMA-g-PHO copolymer were carried out in a phosphate buffer saline (pH 7.4) medium. The hydrolytic degradation of the copolymer was strongly dependent on the degree of grafting (DG) of the PEGMA group. The degradation rate of the copolymer films in vitro increased with increasing DG of the PEGMA group on the PHO chain. The copolymer films showed a controlled delivery of ibuprofen to the medium in periods of time that depend on the composition, hydrophilic/hydrophobic characteristics, initial drug loading amount and film thickness of the graft copolymer support. The drug release rate from the grafted copolymer films was faster than the rate of weight loss of the films themselves. In particular, a combination of the low DG of the PEGMA group in the PHO chains with the low ibuprofen solubility in water led to long-term constant release from these matrices in vitro.     

Side-chain effect of second monomer units on crystalline morphology, thermal properties, and enzymatic degradability for random copolyesters of (R)-3-hydroxybutyric acid with (R)-3-hydroxyalkanoic acids

Three types of random copolymers with 94 mol % (R)-3-hydroxybutyric acid (3HB) and 6 mol % (R)-3-hydroxyalkanoic acids with different side-chain lengths, (R)-3-hydroxypentanoic acid (3HV), (R)-3-hydroxyhexanoic acid (3HHx), and medium-chain-length (R)-3-hydroxyalkanoic acids (mcl-3HA, C8-C12), were prepared by biological synthetic techniques. The solid-state structure and thermal properties of melt-crystallized films for copolymers were characterized by means of wide-angle X-ray diffraction, small-angle X-ray scattering, differential scanning calorimetry, and optical microscopy. The randomly distributed second monomer units, except for 3HV in copolyesters, act as defects of the P(3HB) crystal and are excluded from the P(3HB) crystalline lamellae. The lamellar thickness of copolymers decreased with an increase in the side-chain length of second monomer units. In addition, the growth rate of spherulites decreased with an increase in the carbon numbers of second monomer units at an identical crystallization temperature. These results indicate that a steric bulkiness of the second monomer unit affects the crystallization of (R)-3HB segments in random copolyesters. An enzymatic degradation test of melt-crystallized copolymer films was carried out in the presence of PHB depolymerase from Alcaligenes faecalis T1. Erosion rate of copolyesters was dependent on both the crystallinity and the lamellar thickness of samples. As the result, the rate of enzymatic degradation for copolymer films increased with an increase in the carbon numbers of second monomer units.     

Enzymatic degradation processes of poly[(R)-3-hydroxybutyric acid] and poly[(R)-3-hydroxybutyric acid-co-(R)-3-hydroxyvaleric acid] single crystals revealed by atomic force microscopy: effects of molecular weight and second-monomer composition on erosion rates

Enzymatic degradation processes of poly[(R)-3-hydroxybutyric acid] (P(3HB)) and poly[(R)-3-hydroxybutyric acid-co-(R)-3-hydroxyvaleric acid] (P(3HB-co-3HV)) single crystals in the presence of PHB depolymerase from Ralstonia pickettii T1 were studied by real-time and static atomic force microscopy (AFM) observations. Fibril-like crystals were generated along the long axis of single crystals during the enzymatic degradation, and then the dimensions of fibril-like crystals were analyzed quantitatively. The morphologies and sizes of fibril-like crystals were dependent on the molecular weight and copolymer composition of polymers. For all samples, the crystalline thickness gradually decreased toward a tip from the root of a fibril-like crystal after enzymatic degradation for 1 h. The thinning of fibril-like crystals may be attributed to the destruction of chain-packing structure toward crystallographic c axis by the adsorption of enzyme. From the real-time AFM images, it was found that at the initial stage of degradation the enzymatic erosion started from the disordered chain-packing region in single crystals to form the grooves along the a axis. The generated fibril-like crystals deformed at a constant rate along the a axis with a constant rate after the induction time. The erosion rate at the grooves along the a axis increased with a decrease of molecular weight and with an increase of copolymer composition. On the other hand, the erosion rate along the a axis, at the tip of the fibril-like crystal, was dependent on only the copolymer composition, and the value increased with an increase in the copolymer composition. The morphologies and sizes of fibril-like crystals were governed by both the erosion rates along the a axis at the grooves and tip of fibril-like crystals. In addition, we were able to estimated the overall enzymatic erosion rate of single crystals by PHB depolymerase from the volumetric analysis.     

Local sequence dependence of polyhydroxyalkanoic acid degradation in Hydrogenophaga pseudoflava

The first order intracellular degradation of various polyhydroxyalkanoic acid (PHA) inclusions in Hydrogenophaga pseudoflava cells was investigated by analyzing the compositional and microstructural changes of the PHA using gas chromatography, (13)C NMR spectroscopy, and differential scanning calorimetry. Two types of PHA, copolymers and blend-type polymers, were separately accumulated in cells for comparison. The constituent monomers were 3-hydroxybutyric acid (3HB), 4-hydroxybutyric acid (4HB), and 3-hydroxyvaleric acid (3HV). It was found that the 3HB-4HB copolymer was degraded only when the polymer contained a minimal level of 3HB units. With the cells containing a 3HB/4HB blend-type polymer, only poly(3HB) was degraded, whereas poly(4HB) was not degraded, indicating the totally inactive nature of the intracellular depolymerase against poly(4HB). On the basis of the magnitude of the first order degradation rate constants, the relative substrate specificity of the depolymerase toward the constituting monomer units was determined to decrease in the order 3HB > 3HV > 4HB. (13)C NMR resonances of the tetrad, triad, and dyad sequences were analyzed for the samples isolated before and after degradation experiments. The results showed that the intracellular degradation depended on the local monomer sequence of the copolymers. The relative substrate specificity of the depolymerase determined from the NMR local sequence analysis agreed well with that obtained from the kinetics analysis. It is suggested that, without isolation and purification of the intracellular PHA depolymerase and "native" PHA substrates, the relative specificity of the enzyme as well as the microstructural heterogeneity of the PHA could be determined by measuring in situ the first order degradation rate constants of the PHA in cells.     

Injectable and sustained delivery of human growth hormone using chemically modified Pluronic copolymer hydrogels

A new injectable biodegradable hydrogel system with thermosensitive sol-gel transition behavior was developed. A series of A-B-A triblock copolymers consisting of Pluronic copolymer end-capped with D- or L-lactic acid oligomers (PL-LA(n)) with various chain lengths (n = 5,12) was synthesized. It was assumed that a pair of two triblock copolymers with enantiomeric oligolactide chains, when blended in an equimolar mixture, would form more stable, self-assembled, and stereocomplexed (ST) hydrogels. A series of blend hydrogels encapsulating human growth hormone (hGH) was prepared by varying blend ratios between PL and stereocomplexed PL copolymers. They showed sustained release of hGH via an erosion-dependent mechanism. The hydrogel with a 5% blending ratio exhibited the most delayed mass erosion as well as sustained protein release patterns in vitro possibly due to the formation of a fish-net like 3-D mesh structure. The effect of incubation condition on hGH release and degradation behaviors was also assessed.     

Photocurable liquid biodegradable copolymers: in vitro hydrolytic degradation behaviors of photocured films of coumarin-endcapped poly(epsilon-caprolactone-co-trimethylene carbonate)

Coumarin-endcapped tetrabranched liquid copolymers composed of epsilon-caprolactone and trimethylene carbonate (TMC), prepared using pentaerythritol or four-branched poly(ethylene glycol) (PEG) as an initiator, were ultraviolet irradiated to produce photocured solid biodegradable copolymers. The hydrolytic degradation behaviors of photocured films were determined from the weight loss of the films. The initial hydrolysis rate (determined for up to 24 h using a quartz crystal microbalance) was enhanced with aqueous solutions of higher pH. The hydrolysis rate in the early period of immersion was increased with an increase in TMC content, whereas that in the later period (week order) decreased with a increase in TMC content. This inverse relation of composition dependence on the hydrolysis rate between the early and late periods was discussed. Topological measurements using scanning electron microscopy and atomic force microscopy as well as depth profiles of the fluorescein-stained hydrolyzed layer showed that for the pentaerythritol-initiated copolymer, irrespective of copolymer composition, hydrolysis occurred at surface regions and surface erosion proceeded with immersion time. For PEG-based copolymers, both surface erosion and bulk degradation occurred simultaneously. The hydrolyzed surfaces became highly wettable with water and exhibited noncell adhesivity.     

Synthesis and characterization of methacrylic derivatives of 5-amino salicylic acid with pH-sensitive swelling properties

The purpose of this study is to develop novel colon-specific drug delivery systems with pH-sensitive swelling and drug release properties. Methacrylic-type polymeric prodrugs with different content levels of 5-amino salicylic acid (5-ASA) were synthesized by free radical copolymerization of metacrylic acid (MAA), polyethylene glycol monomethacrylate (PEGMA), and a methacrylic derivative of 5-ASA (methacryloyloxyethyl 5-amino salicylate [MOES]). The copolymers were characterized, and the drug content of the copolymers was determined. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). The swelling and hydrolytic behavior of the copolymers was dependent on the content of MAA groups and caused a decrease in gel swelling in SGF or an increase in gel swelling in SIF. Drug release studies showed that increasing content of MAA in the copolymer enhances the hydrolysis in SIF but has no effect in SGF. The results suggest that hydrogen-bonded complexes are formed between MAA and PEG pendant groups and that these pH-sensitive systems could be useful for preparation of a controlled-release formulation of 5-ASA.     

Mass spectrometric and kinetic studies on slow progression of papain-catalyzed polymerization of L-glutamic acid diethyl ester

Papain polymerizes L-glutamic acid diethyl ester (Glu-di-OEt) regioselectively, resulting in the formation of poly (gamma-ethyl alpha-L-glutamic acid) with various degrees of polymerization of less than 13. Reaction temperatures below 20 degrees C were appropriate for the reaction in terms of suppression of non-enzymatic degradation of Glu-di-OEt and an increase in the peptide yield, while the reaction was preceded by a pronounced induction period. Mass spectrometric analyses of the reaction conducted at 0 degrees C revealed that the accumulation of the initial dimerization product, L-glutamyl-L-glutamic acid triethyl ester (Glu-Glu-tri-OEt), was limited during the induction period, and that a sequential polymer derived from a further elongation of the dimer was the tetramer, but not the trimer. Kinetic analyses of acyl transfer reactions with Glu-di-OEt and Glu-Glu-tri-OEt as acyl acceptors and Nalpha-benzoyl-L-arginine ethyl ester as an acyl donor affirmed that Glu-Glu-tri-OEt bound more strongly than Glu-di-OEt both to the S- and S'-subsites of papain. Therefore, what occurred during the initial stage of the polymerization was interpreted as follows: the rate of the papain-catalyzed dimerization of Glu-di-OEt was extremely slow, once Glu-Glu-tri-OEt was initially synthesized it exclusively bound to the active site of papain, and then papain utilized the dimer in polymerization effectively rather than the monomer.     

Inhibition of cathepsin K with lysosomotropic macromolecular inhibitors

Cathepsin K is the major enzyme responsible for the degradation of the protein matrix of bone and probably for the destruction of articular cartilage in rheumatoid arthritis joints. These processes occur mainly in the resorption lacuna and within the lysosomal compartment. Here, we have designed, synthesized, and evaluated new lysosomotropic (water-soluble) polymer-cathepsin K inhibitor conjugates. In particular, we characterized the relationship between conjugate structures and their activity to inhibit cathepsins K, B, L, and papain. A potent selective cathepsin K inhibitor, 1,5-bis(N-benzyloxycarbonylleucyl)carbohydrazide, was modified to 1-(N-benzyloxycarbonylleucyl)-5-(phenylalanylleucyl)carbohydrazide (I) to facilitate polymer conjugation. It was conjugated to the polymer chain termini of two water-soluble polymers [alpha-methoxy poly(ethylene glycol), abbreviated as mPEG-I; semitelechelic poly[N-(2-hydroxypropyl)methacrylamide], abbreviated as ST-PHPMA-I]. The conjugation of inhibitor I to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer side chains was accomplished via either a Gly-Gly spacer (PHPMA-GG-I) or with no spacer between I and the copolymer backbone (PHPMA-I). Kinetic analysis revealed that free inhibitor I possessed an apparent second-order rate constant against cathepsin K (k(obs)/[I] = 1.3 x 10(6) M(-1) s(-1)) similar to that of unmodified 1,5-bis(Cbz-Leu) carbohydrazide, while I conjugated to the chain termini of mPEG and ST-PHPMA-COOH had slightly lower values (about 5 x 10(5) M(-1) s(-1)). The k(obs)/[I] values for I attached to the side chains of HPMA copolymers (PHPMA-GG-I and PHPMA-I) were about 3 x 10(4) M(-1) s(-1). When tested against cathepsin L, inhibitor I and all its polymer conjugates produced k(obs)/[I] values 1-2 orders of magnitude less than those determined for cathepsin K, while for cathepsin B and papain, the values were 2-4 orders of magnitude lower. The ability of mPEG-I and ST-PHPMA-I to inhibit cathepsin K activity in synovial fibroblasts was also evaluated. Both polymer-bound inhibitors were internalized by endocytosis and were ultimately trafficked to the lysosomal compartment. ST-PHPMA-I was internalized faster than mPEG-I. The inhibitory activity in the synovial fibroblast assay correlated with the rate of internalization.     

Investigating the structure-property relationship of bacterial PHA block copolymers

Mechanical testing of solvent cast films consisting of short-chain-length (SCL) polyhydroxyalkanoate (PHA) films suggested that films consisting of block copolymers retained more elasticity over time with respect to films of similar random copolymers of comparable composition. Two experimental techniques, wide angle X-ray scattering (WAXS) and uniaxial extension, were used to quantitatively investigate the structure-property relationship of bacterially synthesized PHA block copolymers of poly(3-hydroxybutyrate) (PHB) homopolymer and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) random copolymer (PHBV) segments. Uniaxial testing experiments yielded the Young's modulus, ultimate tensile strength, and the elongation until fracture of the films. Percent crystallinity was determined by deconvolution of amorphous and crystalline scattering peaks obtained from WAXS. Two PHBV films containing either 8% 3-hydroxyvalerate monomer (3HV) or 29% 3HV exhibited a quick transition to brittle behavior, decreasing to less than 20% percent elongation at fracture within a few days after annealing. Conversely, the block copolymer samples remained higher than 100% elongation at fracture a full 3 months after annealing. Because block copolymers covalently link polymers that would otherwise form thermodynamically separate phases, the rates and degrees of crystallization of the block copolymers are less than the random copolymer samples. These differences translate into materials that extend the property space of biologically synthesized SCL PHA.     

Structure-property relationships of copolymers obtained by ring-opening polymerization of glycolide and epsilon-caprolactone. Part 2. Influence of composition and chain microstructure on the hydrolytic degradation

A series of glycolide/epsilon-caprolactone copolymers were compression molded and allowed to degrade in a pH 7.4 phosphate buffer at 37 degrees C. Degradation was monitored by various analytical techniques such as (1)H NMR, X-ray diffraction, DSC, CZE, ESI-MS, and inherent viscosity measurements. The results show that the degradation rate depends not only on the copolymer composition but also on its chain microstructure. Generally, copolymers with a higher C-G bond content or a higher degree of randomness exhibit higher degradation rates. Sequences with odd numbers of glycolyl units such as -CGC- and -CGGGC-, which result from the second mode transesterification, appear more resistant to hydrolysis. As a consequence, degradation residues obtained at the later stages of degradation are mainly composed of long glycolyl and caproyl sequences linked by -CGC- and -CGGGC- ones. The degradation rate of the copolymers depends also on the degree of crystallinity of each component which is related to the block length. The caproyl component can be preferentially degraded if it is in the amorphous state and the glycolyl component is semicrystalline.     

Amino acid sequence of chicken liver cathepsin L

The complete amino acid sequences of the heavy and light chains of chicken liver cathepsin L have been determined by automated gas-phase Edman degradation. The heavy and light chains contained 176 and 42 amino acid residues respectively. A glucosamine-based oligosaccharide group was attached to Asn-109 of the heavy chain. Chicken liver cathepsin L had high sequence homology with rat cathepsin H, but exhibited less similarity with rat cathepsin B. Comparisons of cathepsin L with plant cysteine proteinases, such as papain, actinidin and aleurain, reveal high degree of homology.     

Synthesis, characterization, and degradation behavior of amphiphilic poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(epsilon-caprolactone)

A series of biodegradable amphiphilic graft polymers were successfully synthesized by grafting poly(epsilon-caprolactone) (PCL) sequences onto a water-soluble poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. The graft copolymers were prepared through the ring-opening polymerization of epsilon-caprolactone (CL) initiated by the macroinitiator PHEA with pendant hydroxyl groups without adding any catalyst. By controlling the feed ratio of the macroinitiator to the monomer, the copolymers with different branch lengths and properties can be obtained. The successful grafting of PCL sequences onto the PHEA backbone was verified by FTIR, 1H NMR, and combined size-exclusion chromatography and multiangle laser light scattering (SEC-MALLS) analysis. The hydrolytic degradation and enzymatic degradation of these graft copolymers were investigated. The results show the hydrolytic degradation rate increases with increasing content of hydrophilic PHEA backbone. While the enzymatic degradation rate is affected by two competitive factors, the catalytic effect of Pseudomonas cepacia lipase on the degradation of PCL branches and the hydrophilicity which depends on the copolymer composition. In situ observation of the degradation under polarizing light microscope (PLM) demonstrates the different degradation rates of different regions in the polymer samples.     

Synthesis and micellization of amphiphilic brush-coil block copolymer based on poly(epsilon-caprolactone) and PEGylated polyphosphoester

A novel biodegradable amphiphilic brush-coil block copolymer consisting of poly(epsilon-caprolactone) and PEGylated polyphosphoester was synthesized by ring opening polymerization. The composition and structure of the copolymer were characterized by 1H NMR, 13C NMR, and FT-IR, and the molecular weight and molecular weight distribution were analyzed by gel permeation chromatograph (GPC) measurements to confirm the diblock structure. These amphiphilic copolymers formed micellar structures in water, and the critical micelle concentrations (CMCs) were around 10(-3) mg/mL, which was determined using pyrene as a fluorescence probe. Transmission electron microscopy (TEM) images showed that the micelles took an approximately spherical shape with core-shell structure, which was further demonstrated by laser light scattering (LLS) technique. The degradation behavior of the polymeric micelle was also investigated in the presence of Pseudomonas lipase and characterized by GPC measurement. Such polymer micelles from brush-coil block copolymers are expected to have wide utility in the field of drug delivery.     

The degradation of cartilage proteoglycans by tissue proteinases. Proteoglycan structure and its susceptibility to proteolysis.

1. Proteoglycan was obtained from bovine nasal cartilage by a procedure involving sequential extraction with a low-ionic-strength KCl solution, then a high-ionic-strength CaCl2 solution. Purification was by CsCl-density-gradient centrifugation. 2. The CaCl2- extracted proteoglycan was subjected to proteolytic degradation by papain, trypsin, cathepsin D, cathepsin B, lysosomal elastase or cathepsin G. Degradation was allowed to proceed until no further decrease in viscosity was detectable. 3. The size and chemical composition of the final degradation products varied with the different proteinases. Cathepsin D and cathepsin G produced glycosaminoglycan-peptides of largest average size, and papain produced the smallest product. 4. The KCl-extracted proteoglycan was intermediate in molecular size and composition between the CaCl2-extracted proteoglycan and the largest final degradation products, and may have been formed by limited proteolysis during the extraction procedure. 5. It is postulated that the glycosaminoglycan chains are arranged in groups along the proteoglycan core protein. Proteolytic cleavage between the groups may be common to the majority of proteinases, whereas clevage within the groups is dependent on the specificity of each individual proteinase.     

Synthesis and characterization of poly(dimer acid-brassylic acid) copolymer and poly(dimer acid-pentadecandioic acid) copolymer

Poly(dimer acid-brassylic acid) [P(DA-BA)] copolymers and poly(dimer acid-pentadecandioic acid) [P(DA-PA)] copolymers were prepared by melt polycondensation of the corresponding mixed anhydride prepolymers. The copolymers were characterized by Fourier transform infrared (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), wide angle x-ray powder-diffraction, and thermal gravimetric analysis (TGA). In vitro studies show that all the copolymers are degradable in phosphate buffer at 37 degrees C, and leaving an oily dimer acid residue after hydrolysis for the copolymer with high content of dimer acid. The release profiles of hydrophilic model drug, ciprofloxcin hydrochloride, from the copolymers, follow first-order release kinetics. All the preliminary results suggested that the copolymer might be potentially used as drug delivery devices.