Fabrication of Poly(D,L-lactide-co-glycolide) Microspheres and Degradation Characteristics in vitro

Poly(D,L-lactide-co-glycolide) (PLGA, 75/25) microspheres were prepared by the emulsion solvent extraction/evaporation technique and their degradation behaviors in vitro at 37°C were investigated. PLGA microspheres with a smooth and nonporous surface were obtained, with a mean particle size of 114.15 μm. It was observed that mass loss and water uptake of PLGA increased with increasing degradation time; however, weight average molecular weight and the pH value of the phosphate buffered saline (PBS) solution decreased. The observed relative rates of mass loss vs. molecular weight decreases were consistent with the explanation that PLGA underwent bulk degradation rather than surface degradation. During the degradation time, the surface of the PLGA microspheres became coarse and there were many micropores that developed upon immersion in the PBS. The microspheres lost their spherical form with increasing degradation time.     

A Comparative Study on In vitro Degradation Behaviors of Poly(L-lactide-co-glycolide) Scaffolds and Films

In vitro degradation behaviors of three-dimensional porous scaffolds and films made from amorphous poly(L-lactide-co-glycolide) (85/15) were systematically investigated up to 12 weeks in phosphate buffer saline (PBS) solution at 37°C. The following properties of the scaffolds and films were compared as a function of degradation time: pH value of PBS, water uptake, weight, molecular mass and its distribution, and morphology. The results show that the films degraded much faster than the scaffolds. The film's degradation was heterogenous due to the increased concentration of the acidic degradation products inside. However, owing to much thinner pore walls, heterogenous degradation due to the autocatalytic effect was not observed in the scaffolds.     

Influence of Bovine Bone Content on In Vitro Degradation of Poly-L-lactic Acid and Bovine Bone Composite Materials

In vitro degradation experiments of poly-L-lactic acid (PLLA) and bovine bone (BB) composites were carried out in a phosphate-buffered solution (PBS) at 37°C with a pH of 7.4. The influence of BB content on pH value of PBS, water uptake, molecular weights, molecular weight distributions, weight losses, mechanical strengths, and morphologies of PLLA/BB was investigated with degradation times. The results indicated that the presence of the BB modified the degradation of the PLLA matrix. The degradation rate of PLLA in the PLLA/BB composite was slower than the degradation rate of the sole PLLA material. Furthermore, the degradation rate of the composites became slower with the increasing content of BB in PLLA/BB composites.     

In-Vitro Degradation Behaviors of Composite Scaffolds Based on 1,4-Butadnediamine Modified Poly(lactide-co-glycolide) and Nanobioceramics

In-vitro degradation behaviors of composite scaffold materials composed of 1,4-butanediamine modified poly(lactide-co-glycolide) (BMPLGA), nanobioactive glass (NBG) and β-tricalcium phosphate (β-TCP) were systematically investigated in phosphate-buffered solution (PBS) at 37?°C. The properties of the BMPLGA/NBG-β-TCP and BMPLGA scaffolds, including the changes of pH value, mass, water uptake, compressive strength and molecular mass, were investigated as a function of degradation time. The results showed that the introduction of the NBG and β-TCP particles played important roles in the degradation of BMPLGA matrix. The degradation rate of the BMPLGA/NBG-β-TCP scaffolds was slower than that of the BMPLGA scaffolds.     

In vitro studies of PEG thin films with different molecular weights deposited by MAPLE

In this work, polyethylene glycol (PEG) films were produced by Matrix Assisted Pulsed Laser Evaporation (MAPLE). The possibility to tailor the properties of the films by means of polymer molecular weight was explored. The films of PEG of average molecular weights 400 Da, 1450 Da, and 10000 Da (PEG₄₀₀, PEG₁₄₅₀, and PEG₁₀₀₀₀) were investigated in vitro, in media similar with those inside the body (phosphate buffer saline PBS with pH 7.4 and blood). The mass of the polymer did not change during this treatment, but the polymer molecular weight was found to strongly influence the films properties and their behavior in vitro. Thus, immersion in PBS induced swelling of the PEG films, which was more pronounced for PEG polymers of higher molecular weight. Prior to immersion in PBS, the PEG films of higher molecular weight were more hydrophilic, the water contact angles decreasing from ～66 grd for PEG₄₀₀ to ～41 grd for PEG₁₄₅₀ and to ～15 grd for PEG₁₀₀₀₀. The same trend was observed during immersion of the PEG films in PBS. Before immersion in PBS, the refractive index of the films increased from ～1.43 for PEG₄₀₀ to ～1.48 for PEG₁₄₅₀ and to ～1.68 for PEG₁₀₀₀₀. During immersion in PBS the refractive index decreased gradually, but remained higher for the PEG molecules of higher mass. Finally, blood compatibility tests showed that the PEG films of higher molecular weight were most compatible with blood.     

Synthesis and Characterization of Terpolymers of poly(L-lactide-glycolide-ε-caprolactone)

Random terpolymers of poly(L-lactide-glycolide-ε-caprolactone) (PLLGC) was prepared by ring-opening polymerization of L-lactide, glycolide and ε-caprolactone monomers initiated with stannous octanoate. Fourier transform infrared spectra, nuclear magnetic resonance and gel permeation chromatography were employed to characterize the obtained PLLGC terpolymers. The effects of polymerization temperature, reaction time, the amount of initiator and the polymerization pressure on the weight average molecular mass and polydispersity index of the PLLGC were investigated. In addition, the water contact angle of the PLLGC was also tested. The characterization of chemical structure showed that the PLLGC was successfully synthesized. For instance, a PLLGC terpolymer with a weight average molecular mass of about 12.435?×?10⁴?Da and a polydispersity index of 1.28 was obtained when the polymerization was conducted with a molar ratio of monomer to initiator ([M]/[I]) of 2000, polymerization temperature of 140?°C, polymerization pressure of 5.0?Pa and reaction time of 24?h. The random incorporation of ε-CL monomer units decreased the wettability of the PLGA copolymers.     

Influence of Degradation of Poly-L-lactide on Mass Loss,Mechanical Properties,and Crystallinity in Phosphate-Buffered Solution

A bulk degradation of poly-L-lactide (PLLA) rectangular bars was studied by incubating them in phosphate-buffered solution at 37°C for different periods. The characteristics of the mass, water uptake, mechanical properties, thermal behavior, and crystallinity of the PLLA samples were investigated. The results indicate that mass loss and water uptake of PLLA increase with increasing time; however, pH value and mechanical strength decrease. The melting temperature, melting enthalpy, and crystallinity of PLLA firstly increase and then decrease with increasing degradation time. There is no new diffraction peak formed with increasing degradation time, which indicates that the degradation could occur in the amorphous regions firstly and then in the crystalline regions.     

The characterization of mechanical and surface properties of poly (glycerol-sebacate-lactic acid) during degradation in phosphate buffered saline

The present study synthesized a poly (glycerol-sebacate-lactic acid) (PGSL) with 1:1:0.5 mole ratio of glycerol, sebacate and lactic acid and investigated the degradation characteristics of the polymer in phosphate buffered saline (PBS) at 37 °C in vitro by means of mass loss tests, geometry, differential scanning calorimeter (DSC) measurements, tensile analysis and scanning electron microscopy (SEM). The maintained geometry, linear mass loss, and minor crack formation on the surface during degradation characterized both the bulk degradation and surface erosion of the polymer. By day 30 of degradation, the mass lost reached 16%. The elastic modulus, tensile strength and elongation at breakage of PGSL were correlative to the period of degradation.     

Influence of ultrasonic processing on the macromolecular properties of poly (d,l-lactide-co-glycolide) alone and in its biocomposite with hydroxyapatite

In this work poly(d,l-lactide-co-glycolide) (PLGA) and a poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HAp) composite processed in an ultrasonic field at higher (25 °C) and lower (8 °C) temperatures were studied with respect to the molecular properties of the obtained materials. The processing of the PLGA and the PLGA/HAp composite in an ultrasonic field resulted in a change of molar mass averages of the polymer/polymeric part of these materials, while an amorphous structure and a 50:50 lactide-to-glycolide co-monomer ratio were preserved without the formation of crystalline oligomers. However, mobility of polymeric chains obtained after ultrasonic processing was lower indicating ordering the structure of polymeric chains as a result of processing. Additionally, it was observed that the mobility of the PLGA macromolecules was lower within the composite in comparison with the mobility of the chains within the PLGA alone in the case when both were obtained after ultrasonic processing. This was a consequence of the structure formation through the interactions between the PLGA and the HAp. Based on these results different degradation rate of PLGA in composite can be expected, which is important in the application of this material for the controlled drug delivery of medicaments.     

In-vitro degradation behavior and biological properties of a novel maleated poly (D,L-lactide-co-glycolide) for biomedical applications

Synthesized biodegradable polymers with controlled degradability and good biological safety would be useful in biomedical applications. In this work a novel maleated poly(D,L-lactide-co-glycolide) (MPLGA) was melt copolymerized from maleic anhydride, D,L-lactide and glycolide monomers. The degradation behavior in phosphate-buffered solution (PBS) was investigated and the biological properties were studied by using fibroblastic cells cultured in an extract of MPLGA and by an in-vitro cell cytotoxicity test. The results indicated that the MPLGA was successfully obtained using the melt-copolymerization method. The maleic anhydride groups in the MPLGA led to a faster degradation in PBS than PLGA. Fibroblastic cells showed normal morphologies in MPLGA extracts, and the MPLGA materials showed no cell cytotoxicity. The in-vitro biological properties indicated that the obtained MPLGA had good biocompatibility and would be useful for medical applications.     

Biocompatible polymeric implants for controlled drug delivery produced by MAPLE

Implants consisting of drug cores coated with polymeric films were developed for delivering drugs in a controlled manner. The polymeric films were produced using matrix assisted pulsed laser evaporation (MAPLE) and consist of poly(lactide-co-glycolide) (PLGA), used individually as well as blended with polyethylene glycol (PEG). Indomethacin (INC) was used as model drug. The implants were tested in vitro (i.e. in conditions similar with those encountered inside the body), for predicting their behavior after implantation at the site of action. To this end, they were immersed in physiological media (i.e. phosphate buffered saline PBS pH 7.4 and blood). At various intervals of PBS immersion (and respectively in blood), the polymeric films coating the drug cores were studied in terms of morphology, chemistry, wettability and blood compatibility. PEG:PLGA film exhibited superior properties as compared to PLGA film, the corresponding implant being thus more suitable for internal use in the human body. In addition, the implant containing PEG:PLGA film provided an efficient and sustained release of the drug. The kinetics of the drug release was consistent with a diffusion mediated mechanism (as revealed by fitting the data with Higuchi's model); the drug was gradually released through the pores formed during PBS immersion. In contrast, the implant containing PLGA film showed poor drug delivery rates and mechanical failure. In this case, fitting the data with Hixson-Crowell model indicated a release mechanism dominated by polymer erosion.     

Preparation and In-vitro Degradation Behavior of Poly(L-lactide-co-glycolide-co-ε-caprolactone) Terpolymer

A random terpolymer of poly(L-lactide-co-glycolide-co-ε-caprolactone) (PLLGC) was synthesized from L-lactide, glycolide and ε-caprolactone. The in-vitro hydrolytic degradation behavior of the PLLGC terpolymer was investigated as a function of the degradation time; the results showed that the degradation rate of PLLGC was lower than that of PLGA due to a reduction in the acidic degradation products. Therefore, we suggest the degradation rate of the PLGA could be controllable by introduction of ε-caprolactone into the PLGA martrix, while the physical properties (mechanical, etc.) were superior to PLGA.     

Characterization of drug-eluting stent (DES) materials with cluster secondary ion mass spectrometry (SIMS)

Secondary ion mass spectrometry (SIMS) employing an SF₅⁺ polyatomic primary ion source was utilized to analyze several materials commonly used in drug-eluting stents (DES). Poly(ethylene-co-vinyl acetate) (PEVA), poly(lactic-co-glycolic acid) (PLGA) and various poly(urethanes) were successfully depth profiled using SF₅⁺ bombardment. The resultant molecular depth profiles obtained from these polymeric films showed very little degradation in molecular signal as a function of increasing SF₅⁺ primary ion dose when experiments were performed at low temperatures (signal was maintained for doses up to ∼5 × 10¹⁵ ions/cm²). Temperature was determined to be an important parameter in both the success of the depth profiles and the mass spectral analysis of the polymers. In addition to the pristine polymer films, paclitaxel (drug released in Taxus™ stent) containing PLGA films were also characterized, where it was confirmed that both drug and polymer signals could be monitored as a function of depth at lower paclitaxel concentrations (10 wt%).     

Resonant infrared pulsed laser deposition of thin biodegradable polymer films

Thin films of the biodegradable polymer poly(DL-lactide-co-glycolide) (PLGA) were deposited using resonant infrared pulsed laser deposition (RIR-PLD). The output of a free-electron laser was focused onto a solid target of the polymer, and the films were deposited using 2.90 (resonant with O-H stretch) and 3.40 (C-H) μm light at macropulse fluences of 7.8 and 6.7 J/cm², respectively. Under these conditions, a 0.5-μm thick film can be grown in less than 5 min. Film structure was determined from infrared absorbance measurements and gel permeation chromatography (GPC). While the infrared absorbance spectrum of the films is nearly identical with that of the native polymer, the average molecular weight of the films is a little less than half that of the starting material. Potential strategies for defeating this mass change are discussed. Received: 22 August 2001 / Accepted: 23 August 2001 / Published online: 17 October 2001     

Micro-molding with ultrasonic vibration energy: New method to disperse nanoclays in polymer matrices

Ultrasound technology was proved as an efficient processing technique to obtain micro-molded specimens of polylactide (PLA) and polybutylene succinate (PBS), which were selected as examples of biodegradable polyesters widely employed in commodity and specialty applications. Operational parameters such as amplitude, molding force and processing time were successfully optimized to prepare samples with a decrease in the number average molecular weight lower than 6%.Ultrasonic waves also seemed an ideal energy source to provide effective disaggregation of clay silicate layers, and therefore exfoliated nanocomposites. X-ray diffraction patterns of nanocomposites prepared by direct micro-molding of PLA or PBS powder mixtures with natural montmorillonite or different organo-modified clays showed the disappearance of the 0 0 1 silicate reflection for specimens having up to 6 wt.% clay content. All electron micrographs revealed relatively homogeneous dispersion and sheet nanostructures oriented in the direction of the melt flow.Incorporation of clay particles during processing had practically no influence on PLA characteristics but enhanced PBS degradation when an organo-modifier was employed. This was in agreement with thermal stability data deduced from thermogravimetric analysis. Cold crystallization experiments directly performed on micro-molded PLA specimens pointed to a complex influence of clay particles reflected by the increase or decrease of the overall non-isothermal crystallization rate when compared to the neat polymer. In all cases, the addition of clay led to a clear decrease in the Avrami exponent.     

Synthesis and characterization of noscapine loaded magnetic polymeric nanoparticles

The delivery of noscapine therapies directly to the site of the tumor would ultimately allow higher concentrations of the drug to be delivered, and prolong circulation time in vivo to enhance the therapeutic outcome of this drug. Therefore, we sought to design magnetic based polymeric nanoparticles for the site directed delivery of noscapine to invasive tumors. We synthesized Fe₃O₄ nanoparticles with an average size of 10±2.5 nm. These Fe₃O₄ NPs were used to prepare noscapine loaded magnetic polymeric nanoparticles (NMNP) with an average size of 252±6.3 nm. Fourier transform infrared (FT-IR) spectroscopy showed the encapsulation of noscapine on the surface of the polymer matrix. The encapsulation of the Fe₃O₄ NPs on the surface of the polymer was confirmed by elemental analysis. We studied the drug loading efficiency of polylactide acid (PLLA) and poly (l-lactide acid-co-gylocolide) (PLGA) polymeric systems of various molecular weights. Our findings revealed that the molecular weight of the polymer plays a crucial role in the capacity of the drug loading on the polymer surface. Using a constant amount of polymer and Fe₃O₄ NPs, both PLLA and PLGA at lower molecule weights showed higher loading efficiencies for the drug on their surfaces.     

Polysaccharides-based polyelectrolyte nanoparticles as protein drugs delivery system

Polysaccharides-based nanoparticles were prepared by synthesized quaternized chitosan and dextran sulfate through simple ionic-gelation self-assembled method. Introduction of quaternized groups was intended to increase water solubility of chitosan and make the nanoparticles have broader pH sensitive range which can remain more stable in physiological pH and decrease the loss of protein drugs caused by the gastric cavity. The load of BSA was affected by molecular parameter, i.e., degree of substitution, and average molecular weight of quaternized chitosan, as well as concentration of BSA. Fast release occurred in phosphate buffer solution (pH 7.4) while the release was slow in hydrochloric acid (pH 1.4). The drug release mechanism is Fickian diffusion through release kinetics analysis. Cell uptake demonstrated nanoparicles can internalize into Caco-2 cells, which suggested that nanoparticles had good biocompatibility. No significant conformation change was noted for the released BSA in comparison with native BSA using circular dichroism spectroscopy. This kind of novel composite nanoparticles may be a promising delivery system for oral protein and peptide drugs.     

Mechanochemical degradation kinetics of high-density polyethylene melt and its mechanism in the presence of ultrasonic irradiation

In this paper, the effect of ultrasonic intensity on the degradation of high-density polyethylene (HDPE) melt, degradation mechanism, ultrasonic degradation kinetics of HDPE melt as well as the development of molecular weight distribution of HDPE melt during ultrasonic degradation were studied. In the initial stage, the ultrasonic degradation of HDPE melt shows a random scission process, and the molecular weight distribution broadens. After that, the ultrasonic degradation of HDPE melt shows a nonrandom scission process, and the molecular weight distribution of HDPE melt narrows with ultrasonic irradiation time. The average molecular weight of HDPE decreases with the increase of ultrasonic intensity and increases and trends forward that of undegraded HDPE with the increase of distance from ultrasonic probe tip, indicating that attenuation of ultrasonic intensity in HDPE melt is very quick. Ultrasonic degradation kinetics of HDPE melt obeys the equation: Mt=M(infinity) + Ae(-kt). The theoretic calculation by this equation accords well with the experimental results. The plausible ultrasonic degradation mechanism of polymer melt based on molecular relaxation was also proposed in this paper.     

Degradation Studies of Polycaprolactone in Banana Fibers Reinforced Thermoplastics Composites

In this paper we report the fabrication, properties and degradation studies of banana fibers–reinforced thermoplastic polymers. In order to impart hydrophobicity to the fibers and also to concomitantly increase interfacial bond strength, which is a critical factor for obtaining better mechanical properties of composites, banana fibers were treated with sodium hydroxide (5% and 10% for 4 h), sebacoyl chloride (SC) (0.5 g, 4 h), or toluene diisocyanate (TDl) (1.5 mL, 4 h). Mechanical properties of banana fibers treated with TDl were not affected to any significant extent, but there was an increase in tensile strength of fibers treated with sodium hydroxide (NaOH). Deterioration in mechanical properties was observed upon SC treatment. In thermograssimetre analogue (TGA) studies fibers showed initial mass loss (6.5%–9.5%) in the 50–150°C temperature region. Major weight loss occurred above 200°C. Scanning electron microscope (SEM) studies revealed an increase in surface roughness after alkali treatment. High density polyethylene (HDPE) modified by blending with poly (ε‐caprolactone) (80:20 w/w) was used as a thermoplastic matrix. Composites were fabricated by using 1 cm long banana fibers; the weight fraction of fibers was varied from 0.05–0.13. An increase in weight fraction of fibers resulted in an increase in tensile strength and modulus and decrease in elongation at break. Thin sheets and dumbbells were used for enzymatic and chemical hydrolysis degradation tests. The degradation of the material was monitored by weight change and loss of mechanical properties. The enzymatic degradation in (PCL) presence of Pseudomonas cepacia lipase (PCL) gave appreciable weight loss in PCL and blended materials.