A simple synthetic route to the formation of a block copolymer of poly(lactic-co-glycolic acid) and polylysine for the fabrication of functionalized, degradable structures for biomedical applications.

This article documents the formation of a block copolymer of poly(lactic-co-glycolic acid) and polylysine via a simple coupling technique using dicyclohexyl carbodiimide (DCC). The resulting polymer has been characterized via UV-Vis spectroscopy, GPC, (1)H NMR, and elemental analysis, is soluble in a wide variety of solvents, and is easily processable, making the technique a simple and practical one for the formation of functionalized, degradable block copolymers for the fabrication of functionalized structures for biomedical applications.

Biodegradable photo-crosslinked poly(ether-ester) networks for lubricious coatings.

Biodegradable poly(ether-ester) networks were synthesized by UV photopolymerization and their lubrication performances were evaluated. Polyethers such as poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and poly(tetramethylene glycol) (PTMG) were copolymerized with oligomers of D,L-lactic acid and terminated with acrylate groups to form photopolymerizable macromers. 1H NMR and IR spectra confirmed the chemical structures of copolymers and diacrylated macromers. Crosslinked polymer networks were formed upon UV-initiated free-radical polymerization. Gel contents, water contents, and contact angles were measured to characterize the crosslinked networks. In vitro degradation times of the crosslinked networks at 37 degrees C in 1 N NaOH varied from 20 min to 7 days depending on the crosslinking density (molecular weight of macromer) and the hydrophilic susceptibility (types of polyethers). The crosslinked polymers were coated on stainless-steel needles to investigate the lubrication properties by measuring penetration and drag forces through rubber stoppers. The maximum improvement in penetration force over control was 41% in the needle coated with PPG-based polymer networks (molecular weight of PPG = 4000). These materials can potentially be used as biodegradable lubricants for coating various medical products to replace the existing non-degradable silicone-based materials currently used.

Bacterial inactivation by using near- and supercritical carbon dioxide.

The three most common methods of sterilization in use today are ethylene oxide exposure, gamma-irradiation, and steam sterilization. Each of these methods has serious limitations for the sterilization of some materials used in medicine, especially thermally and hydrolytically sensitive polymers by themselves and in combination with proteins. In this work, we demonstrate a potential new method of sterilization by using supercritical fluid carbon dioxide. Using this method we achieve complete inactivation of a wide variety of bacterial organisms at moderate temperatures and in the absence of organic solvents or irradiation. Sterilization is a function of both the proximity to the fluid's critical point and the chemical nature of the fluid itself. When biodegradable polymers poly(lactic-co-glycolic) acid and polylactic acid were included in the sterilization process, there was no effect on the inactivation efficiency, yet no physical or chemical damage to these thermally and hydrolytically labile materials was observed.

Microparticles of novel branched copolymers of lactic acid and amino acids: preparation and characterization.

The preparation and characterization of microparticles produced from a new class of functionalized, biodegradable, comblike graft copolymers is presented. The copolymers are polyester-polyamino acid hybrids, composed of a poly(L-lactic acid-co-L-lysine) (PLAL) backbone, and poly(L-lysine), poly(D,L-alanine) or poly(L-aspartic acid) side chains extending from the lysine residues of PLAL. The microparticles have been characterized with regard to their surface properties, morphology, and size. Thus, electron spectroscopy for chemical analysis data and results of Zeta potential measurements suggest that the polyamino acid side chains tend to concentrate at the surface of the particles. Also, analyses by environmental scanning electron microscopy and confocal scanning laser microscopy indicate that particles carrying poly(lysine) chains have an unusual porous structure, most probably due to the combined effects of the amphiphilic, polyelectrolyte, and chemical nature of the composing copolymer, as well as of the particular preparation technique employed. The capabilities of the microparticles to serve as carriers in controlled drug release and delivery devices were demonstrated by encapsulation and release of rhodamine B, a low molecular weight drug model.

Characterization and development of RGD-peptide-modified poly(lactic acid-co-lysine) as an interactive, resorbable biomaterial.

The design of biomaterials containing specific ligands on the surface offers the possibility of creating materials that can interact with and potentially control mammalian cell behavior. Biodegradable materials further provide the significant advantage that the polymer will disappear in vivo, obviating long-term negative tissue responses as well as the need for retrieval. In earlier studies we synthesized and characterized arginine-glycine-aspartic acid (RGD) peptide-modified poly(lactic acid-co-lysine) (PLAL). In this study, both bulk properties and surface features have been characterized, with a focus on surface analysis as a means of interpreting observed changes in cell behavior. Bulk peptide attachments were performed using 1,1'-carbonyldiimidazole (CDI). Amino groups were measured using colorimetric assays and X-ray photoelectron spectroscopy (XPS). Peptides were measured by incorporating iodine into the peptide as a distinct elemental marker for use with XPS. Typical samples contained 13 +/- 4 pmol/cm2 of amino groups and 4 +/- 0.2 pmol/ cm2 of peptides, as calculated from XPS measurements of nitrogen and iodine. The wettability and crystallinity of the samples were determined by contact angles and differential scanning calorimetry, respectively. Wettability and crystallinity were not altered by the incorporation of lysine or peptides. After incubating bovine aortic endothelial (BAE) cells for 4 h on surfaces with RGD-containing peptides, the mean spread cell area increased from 77 +/- 2 microns2 to 405 +/- 29 microns2 compared to 116 +/- 11 microns2 on poly(lactic acid), 87 +/- 4 microns2 on PLAL, and 105 +/- 4 microns2 on surfaces with RDG-containing (control) peptides. The significance of this work is that the first synthetic interactive, resorbable biomaterial has been developed, and use of this material to control cell behavior has been demonstrated.

Nanotechnology for biomaterials engineering: structural characterization of amphiphilic polymeric nanoparticles by 1H NMR spectroscopy.

Nanoparticles composed of diblock poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) or a branched, multiblock PLA-(PEG)3 were prepared by the single emulsion technique. Results of previous studies of these nanoparticles suggested that their structure is of the core-corona type with a polyester core and an outer PEG coating. In the present study, 1H NMR spectroscopy was utilized to provide direct evidence of the structure of these nanoparticles suspended in an aqueous environment. The results confirm the existence of the core-corona structure under these conditions, and show that the PEG moieties extend out from the nanoparticle core into the aqueous environment, and exhibit chain mobility similar to that of PEG in solution.

Colorimetric analysis of surface reactive amino groups on poly(lactic acid-co-lysine):poly(lactic acid) blends.

The quantification of functional amino (NH2) groups on poly(lactic acid-co-lysine):(poly(L-lactic acid (PLAL:PLA) blends was performed using a colorimetric assay based on the reaction of sulpho-succinimidyl-4-O-(4,4'-dimethoxytrityl)-butyrate (sulpho-SDTB) with primary amino groups. The colorimetric assay was used to assess the available reactive sites for coupling of biologically active species to PLAL. Blends were created that contained from 10 to 70 wt% poly(lactic acid-co-lysine). Bulk lysine contents within the blends were determined by amino acid analysis and ranged from 9.1 micromol g(-1) to 52.9 micromol g(-1) for blends created using PLA of 100000g mol(-1) molecular weight. Surface amino group concentrations on the same set of blends ranged from 0.23 to 1.45 nmol cm(-2). Similar surface amino groups concentrations were measured on blends using 50000, 200000 and 300000g mol(-1) poly(lactic acid). Non-specific interactions of the colorimetric assay reagents with the PLAL-containing blends were measured on blends prepared from epsilon-amino protected PLAL and 100000g mol(-1) PLA. The presence of amino groups within the top 50 angstroms was confirmed by X-ray photoelectron spectroscopy.