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Thermo-mechanical Properties of poly ε-caprolactone/poly L-lactic acid Blends: Addition of Nalidixic acid and polyethylene glycol additives
Abstract
The search for ideal biomaterials is still on-going for tissue regeneration. In this study, blends of poly ε-caprolactone (PCL) with poly l-lactic acid (PLLA), nalidixic acid (NA) and polyethylene glycol (PEG) were prepared. Mechanical and thermal properties of the blends were investigated by tensile and flexural analysis, DSC, TGA, WXRD, MFI, BET, SEM and hot stage optical microscopy. Results showed that the loading of PLLA caused a significant decrease in tensile strength and almost total eradication of the elongation at break of PCL matrix, especially after PEG and NA addition. Increased stiffness was also noted with additional NA, PEG and PLLA, resulting in an increase in the flexural modulus of the blends. Isothermal degradation indicated that bulk PCL, PLLA and the blends were thermally stable at 200°C for the duration of 2h making extrusion of the blends at this temperature viable. Morphological study showed that increasing the PLLA content and addition of the very low viscosity PEG and powder NA decreased the Melt Flow Indexer and increased the viscosity. At the higher temperature, the PLLA begins to soften and eventually melts allowing for increased flow and, coupling this with, the natural increase in MFI caused by temperature is enhanced further. The PEG and NA addition increased dramatically the pore volume which is important for cell growth and flow transport of nutrients and metabolic waste.
Copyright © 2015 Elsevier Ltd. All rights reserved.
... PCL was used in the longterm delivery of female hormones in the product Capronor, a 1-year contraceptive [15] and for mitomycin C in bladder tumours delivery [16]. The high permeability to a wide range of therapeutic drugs and a lack of toxicity has therefore made PCL and its derivatives well suited for controlled drug delivery [17][18][19][20][21][22][23][24]. Recently we demonstrated that the thermo-mechanical properties of PCL can be easily adjusted through the addition of polylactic acid (a biodegradable polymer that improves the biodegradability of the blend) and polyethylene glycol (PEG, acting as a pore former), and was also affected by the presence of a model low dosage (5%) bioactive, nalidixic acid (NA) [22,25]. ...
... The high permeability to a wide range of therapeutic drugs and a lack of toxicity has therefore made PCL and its derivatives well suited for controlled drug delivery [17][18][19][20][21][22][23][24]. Recently we demonstrated that the thermo-mechanical properties of PCL can be easily adjusted through the addition of polylactic acid (a biodegradable polymer that improves the biodegradability of the blend) and polyethylene glycol (PEG, acting as a pore former), and was also affected by the presence of a model low dosage (5%) bioactive, nalidixic acid (NA) [22,25]. Furthermore, it was found that both the solubility of NA in PCL and its in vitro dissolution rate from a PCL matrix could be significantly optimised by varying the cooling rate used during the pressing of the extrudate into plaques [5]. ...
... Methodologies for the melt flow index (MFI) of the blends, as well as hot stage optical microscopy (HSOM) and scanning electron microscopy (SEM) analysis of the pellets, have been described previously [5,22]. ...
Safer pharmaceutical and medical device excipients are being sought as alternatives to polyvinyl polymers that are commonly plasticised by carcinogenic phthalates. This paper demonstrates a biodegradable and non-toxic bioactive polymer matrix that can be easily modified through plasticiser addition in the presence of low dosage active pharmaceutical ingredient (API). Poly(ε-caprolactone) (PCL) was selected as an alternative polymer to polyvinyls as it is biodegradable and has high amorphous content, which improves drug solubility. Bulk PCL and various blends with 5 and 25% polyethylene glycol (PEG, a plasticiser and pore former) and 5% nalidixic acid (NA, the API) were processed using extrusion and pressed into plaques. The resultant material properties were investigated in terms of microscopic, morphological and topographical modification. No evidence of miscibility was found by IR. The rheology and contact angle of the matrix could be easily manipulated through the addition of PEG. Increased loading of PEG to 25% (w/w) caused a 10-fold increase in the melt flow index, a similar increase in the elongational viscosity, and a contact angle decrease of 10°, indicating that the resultant fluid was becoming more Newtonian. It was concluded that the structural and rheological properties of the blend, while easily modified through the addition of PEG, were unaffected by the monodispersion of the API, nalidixic acid.
... PCL blends/compounds are used in sutures, ultra-thin films for dressing cutaneous wounds [6], contraceptive and fixation devices [7,8], dentistry as root fillings [9] and pharmaceutical applications for manufacturing polymeric devices for controlled drug delivery [10]. Dosage formulations for drug delivery have received excessive attention as they can transfer drugs, genes and proteins via various administration routes, including intravenous, ocular, nasal and oral [11]. A previous study has focused on controlling the release profile of a model active pharmaceutical ingredient (API), the antibacterial nalidixic acid (NA), from PCL by blending with PEG [10]. ...
... However, there are only very few publications studying the influence of conditions and processing procedures on the final mechanical and thermal properties of the system [12]. We have already reported our investigation of the effect of PLLA addition on the thermo-mechanical properties of PCL/NA blends [11]; here we report on the effect of PEG on the mechanical and thermal properties of PCL/NA blends as prepared by hot melt extrusion. PEG is approved by FDA for use in medical devices, it is commonly used for PEGylation and it can transfer its properties to other molecules by covalent bonding, which can result in toxic molecules becoming non-toxic and hydrophobic molecules becoming soluble at certain ratios [13,14]. ...
... Full details regarding the polymers physical properties and reason of selection can be found in [10,11]. NA's chemical formula is C12H12N2O3 and is chemically known as 1,4-dihydro-1-ethyl-7-methyl-4-oxo-1,8-naphthridine-3-carboxylic acid. ...
This paper investigates the effects of polyethylene glycol (PEG), on the mechanical and thermal properties of nalidixic acid/ploy ε-caprolactone (NA)/PCL blends prepared by hot melt extrusion. The blends were characterized by tensile and flexural analysis, dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis and X-ray diffraction. Experimental data indicated that the addition of NA caused loss of the tensile strength and toughness of PCL. Thermal analysis of the PCL showed that on addition of the thermally unstable NA, thermal degradation occurred early and was autocatalytic. However, the NA did benefit from the heat shielding provided by the PCL matrix resulting in more thermally stable NA particles. Results show that loading PEG in the PCL had a detrimental effect on the tensile strength and toughness of the blends, reducing them by 20-40%. The partial miscibility of the PCL-PEG system, causes an increase in Tg. While increases in the crystallinity is attributed to the plasticisation effect of PEG and the nucleation effect of NA. The average crystal size increased by 8% upon PEG addition.
... Olewnik-Kruszkowska et al. [125] used PCL as a plasticizer for PLA and observed an enhanced degradation rate of PLA due to the disruption of the crystallization. Alternately, Douglas and colleagues [126] assessed PCL/PLLA blends with PEG and the antibiotic nalidixic acid. They observed that PLLA reduced elongation properties when it was incorporated into PCL, but that this effect could be recovered with the addition of PEG, potentially due to chain lubrication. ...
Polycaprolactone (PCL) is a biodegradable polymer that is widely utilized for biomedical applications, as well as for environmentally sustainable packaging. The mechanisms driving PCL degradation appear to be overall variably documented and investigated, despite the potentially significant influence that aspects such as synthesis, end-group chemistry, molecular weight, and crystallinity, both before and after melt processing, may have on the behavior of the polymer over time. In this review, we identify mechanisms of PCL degradation across a range of mainly biomedical applications, exploring the role of the polymer structure and form, radical interactions, temperature, pH, enzymatic activity, and cellular phagocytosis. We examine how polymer chemistry has been used to alter PCL degradation rates and mechanisms, and present cases where such manipulations may affect the applications of PCL. We also comprehensively discuss the literature assessing the degradation of PCL in vitro and in vivo, and present a summary of the correlations and trends between the data. Significantly, our analysis identifies currently undescribed trends in PCL degradation. Namely, we observe that molecular weight decreases at a consistent rate regardless of the initial value, and does so at a linear rate in vitro and an exponential rate in vivo. Both mechanical properties and mass loss are strongly influenced by construct geometry and environmental conditions.
We further assess the current biomedical literature on the degradation of PCL copolymers and its composites. The formation of novel PCL copolymers or composites is often used to broaden the versatility and applicability of the polymer, although this approach is rarely explored beyond initial research. Novel biomaterials overall rarely emerge from research, with inherent issues such as the reproducibility of synthesis, manufacturing, or characterization methods and outcomes further impeding their translation. We conclude the review with a summary of the current state of the tailorability of PCL-based polymers and composites, and offer recommendations for the future research direction of the field.
... Several formulation approaches and manufacturing techniques to prepare ASDs containing poorly water soluble APIs have been introduced, for example spray drying (SD), hot melt extrusion (HME) and freeze drying (FD) (Douglas et al., 2015;Kumar et al., 2014;Cerdeira et al., 2013). Among these, spray drying is being more and more utilised to develop solid molecular dispersions of poorly soluble drugs (Hengsawas Surasarang et al., 2016;Sawicki et al., 2016) resulting in enhanced solubility and the development of sustained and targeted drug delivery systems. ...
A range of 17 ternary formulations of itraconazole (ITZ), HPMCP and Soluplus have been manufactured using spray drying. These amorphous solid dispersions (ASDs) were very stable against crystallisation and ITZ was found to be amorphous in all formulations after one year at 40 °C/75% RH. A number of solid state analytical techniques including PXRD, DSC, small angle X-ray scattering, FTIR and solid state NMR were used to characterise the physicochemical properties of the ASDs following processing and storage and to assess any interactions between components. Microtrac laser scattering analysis revealed a relationship between polymer levels and particle size distribution (PSD). Dissolution studies indicated that higher Soluplus content in the formulation resulted in higher concentrations of ITZ in acidic media.
... The addition of PEG 400 increased the mass ratio of membrane, the heat flux to the membranes decreased and then decomposition rate was reduced [42]. The incorporation of the PEG has been reported to decrease the thermal decomposition temperature of PLA in PCL/PLA and PLA/PEG blends [43][44][45]. On the other hand, the PLA and PLA-PEG solutions exhibited the two-step degradation processes. ...
Porous PLA structure has been widely used in cell transplantation, drug carrier and wound dressing. The porous structure can be controlled depending on the choice of the polymer, solvent, nonsolvent and preparation parameters. In this study, the porous PLA matrix membranes were prepared by adding PEG 400 in PLA solution using dichloromethane (DCM) as solvent prior to casting. The influence of other liquids as co-solvent on pore formation and the structural change during membrane formation were evaluated. The co-solvents affected both porous topography and mechanical properties of PLA membrane. The porous matrix were produced when the non-solvent of PLA was used as co-solvent. Cryo-SEM micrographs revealed that PEG 400 still remained in the PLA porous matrix membrane. From the tracking of the structural change during film formation, the PLA–PEG solution changed into porous structure by liquid liquid phase separation and solidification processes, respectively. Thermogravimetric analysis revealed that PLA–PEG in DCM solution exhibited the two-step of weight loss, the first step occurred from DCM evaporation and the second step occurred from the degradation of PLA–PEG matrix. The liquid–liquid phase separation and solidification started when the amount of DCM was higher than PEG 400 for 2.67 folds and DCM amount was equal to that of PEG 400, respectively. These results could clarify the pore formation mechanism of porous PLA membrane and will be useful for the further investigation and application.
Research has been conducted on the manufacture of PLA Coir Bentonite composites. This study aims to examine the effect of PLA on mechanical strength with the addition of coir and bentonite fillers from North Aceh and Central Aceh. The sample formulations used were single polymer PLA/Coir and PLA/Coir with variations of filler Bentonite Aceh Utara and Aceh Tengah with 2, 4, 6 and 8% respectively. The combination of PCa samples showed the highest bacterial colony growth rate, which was more than 100 colonies/gram during the 1 week testing period. In the PBATd filler mixture sample, the maximum bacterial test value was 65 colonies/gram and the minimum value contained in the PBAUa sample was 105 colonies/gram. The best tensile strength was obtained in the PBATc sample, namely 65 MPa. PBATd samples began to degrade at 370.15oC compared to PCa samples degraded at 280.21oC. While the PBAUa sample began to degrade at a temperature of 282.11oC. The surface structure of the PCa sample is more homogeneous because there is no bentonite filler mixture, but it is brittle and crumbles easily. For the PBATd sample, the surface structure is smoother and more homogeneous compared to the PBAUa sample.
In the currently rapidly developing field of soft robots, smart materials with controllable properties play the central role. Thermosensitive elastomers are soft, smart materials whose material properties can be controlled by changing their temperature. The aim of this work is to investigate the mechanical properties, to analyze the surface, the inner structure, and the heat transfer within the thermosensitive elastomer materials. This should provide a knowledge base for new combinations, such as a combination of thermosensitive and the well‐known magneto sensitive elastomers, in order to realize new applications. Thermoplastic polycaprolactone particles were incorporated into a flexible polydimethylsiloxane matrix to produce thermosensitive elastomer samples. With a low melting point in the range of 58–60°C, polycaprolactone offers good application potential compared to other thermoplastic materials such as polymethamethylacrylate with a melting point above 160°C. Test samples of different material compositions and geometries were made to examine temperature‐depending material properties. Two useful effects were identified: temperature‐dependent change in stiffness and the shape memory effect. In certain examinations, carbonyl iron particles were also included to find out if the two particle systems are compatible with each other and can be combined in the polydimethylsiloxane matrix without disadvantages. Changes in shore hardness before and after the influence of temperature were investigated. Micro computed tomography images and scanning electron microscopy images of the respective samples were also obtained in order to detect the temperature influence on the material internally as well as on the surface of the thermosensitive elastomers in combination with carbonyl iron particles. In order to investigate the heat transfer within the samples, heating tests were carried out and the influence of different particle concentrations of the thermosensitive elastomers with and without carbonyl iron particles was determined. Further work will focus on comprehensive investigations of thermo‐magneto‐sensitive elastomers, as this will enable the functional integration in the material to be implemented with increased efficiency. By means of the different investigations, the authors see future applications for this class of materials in adaptive sensor and gripper elements in soft robotics.
In this work, the application of various mesoporous silica grades in the preparation of stabilized ternary amorphous solid dispersions of Felodipine using hot melt extrusion was explored. We have demonstrated the effectiveness of mesoporous silica in these dispersions without the need for any organic solvents i.e., no pre-loading or immersion steps required. The physical and chemical properties, release profiles of the prepared formulations and the surface concentrations of the various molecular species were investigated in detail. Formulations containing 25 wt% and 50 wt% of Felodipine demonstrated enhanced stability and solubility of the drug substance compared to its crystalline counterpart. Based on the Higuchi model, ternary formulations exhibited a 2-step or 3-step release pattern which can be ascribed to the release of drug molecules from the organic polymer matrix and the external silica surface, followed by a release from the silica pore structure. According to the Korsmeyer-Peppas model, the release rate and release mechanism are governed by a complex quasi-Fickian release mechanism, in which multiple release mechanisms are occurring concurrently and consequently. Stability studies indicated that after 6 months storage of all formulation at 30% RH and 20 oC, Felodipine in all formulations remained stable in its amorphous state except for the formulation comprised of 40 wt% Syloid AL-1FP with a 50 wt% drug load.
Polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) have been extensively studied for their use in film formation. Poloxamer 407 (P407) is a block copolymer that has thermo-responsive and surfactant properties when used in pharmaceutical systems. These polymers are already used in liquid or semi-solid systems for ocular and parenteral drug delivery. However, the effect of P407 presence in solid pharmaceutical films composed of different PVA:PVP ratios have not been investigated yet. Therefore, this work investigated the influence of P407 added to the binary polymer mixture of PVA and PVP for the development of solid films aiming for pharmaceutical applications. The rheological properties of dispersions were investigated, and films were prepared by solvent casting method using different P407:PVA:PVP ratios according to a factorial design 2³ (plus center point). The mechanical and in vitro mucoadhesive properties of films, as well as the disintegration time were investigated. Systems presented high mechanical resistance, mucoadhesion, and disintegration timeless than 180 s. It was found that higher concentrations of PVA increase mechanical properties and decrease disintegration time, and higher proportions of PVP and P407 increased mucoadhesion. The films could be classified as fast disintegrating films and represent a promising alternative for modifying drug delivery and pharmaceutical applications.
The formation of composite from polymer mixture PCL / PLA / Chitosan bentonite was carried out through the melt intercalation method using an extruder at 180 °C with a holding time of 20 minutes. Bentonite is obtained from Kab. North Aceh which has been modified with CTAB surfactant. The sample formulations used were single PCL and PCL polymers each given 3, 5 and 8 % chitosan fillers. A mixture of PCL / PLA (50: 50) was given 3, 5 and 8 % chitosan / bentonite fillers. The sample is a white plastic rod (bone) material which is tested for its nature through several types of characterization. Modified bentonite and chitosan have an effect on increasing the mechanical and thermal properties of PCL, PLA and mixture polymers both based on the results of tensile test, TGA test (thermal) and bacterial test. PCL / PLA 50:50 with the addition of 8 % bentonite-chitosan filler is the most perfect composition which provides the best test value.
As one of the predominant 3D additive manufacturing technology, fused deposition modeling (FDM) suffers from the rich printable filaments. The goal of this paper is to produce a fully biodegradable polymeric composite filament by blending polylactic acid (PLA) with polycaprolactone (PCL). The effect of PCL content on the geometry, size, roughness and ultimate tensile stress of PLA/PCL composite filaments was investigated, and mechanical properties of the printed components were tested. The results indicate that, with the increase of PCL content, the diameter and ultimate tensile stress gradually decreased, while the surface roughness gradually increased. Due to the toughing effect, with an increase in PCL content, the tensile strength of parts decreased, while the elongation at break and the impact strength kept rising. It was found the parts printed with the addition of 20% of PCL composite filament exhibits the optimal comprehensive performance.
Porous biodegradable PLLA membranes, which can be used as supports for perfusion cell culture systems were designed, developed and characterized. PLLA membranes were prepared via diffusion induced phase separation (DIPS). A glass slab was coated with a binary PLLA–dioxane solution (8 wt.% PLLA) via dip coating, then pool immersed in two subsequent coagulation baths, and finally dried in a humidity-controlled environment. Surface and mechanical properties were evaluated by measuring pore size, porosity via scanning electron microscopy, storage modulus, loss modulus and loss angle by using a dynamic mechanical analysis (DMA). Cell adhesion assays on different membrane surfaces were also performed by using a standard count method. Results provide new insights into the foaming methods for producing polymeric membranes and supply indications on how to optimise the fabrication parameters to design membranes for tissue cultures and regeneration.
The development of binary polymeric mixtures (polymer blends) containing bioadhesive and thermoresponsive polymers can provide new materials for biomedical applications, with higher contact, increased adhesion, prolonged residence time, protection, and in determined cases, secured absorption of an active agent from the site of application. Mixtures were prepared using a wide range of poloxamer 407 and Carbopol 971P(®) amounts. The rheological (flow and oscillatory), sol-gel transition temperature, mechanical (hardness, compressibility, adhesiveness, cohesiveness and elasticity), softness, and mucoadhesive properties of formulations were investigated. Moreover, the interaction between the different proportions of polymers was also analyzed. Continuous shear and oscillatory rheometry identified the plastic flow with various degrees of thixotropy, besides the viscoelastic behavior of formulations. The determination of gelation temperature displayed values ranged from 27.17 to 41.09°C. It was also found that low carbomer concentrations were enough to provide positive interaction parameter. However, the highest values were obtained for the polymeric blends with higher concentration of poloxamer 407. The mucoadhesion and softness index were greater in preparations containing 20% (w/w) poloxamer 407. The rheological, mechanical and mucoadhesive properties of the polymeric blends can be manipulated by changing the concentrations of the polymers and they suggest the blends are worthy of biomedical applications.
Poly(ε-caprolactone) (PCL) is a ductile, bioabsorbable polymer that has been employed as a blend partner for poly(L-lactic acid) (PLLA). An improvement of the material strength and impact resistance of PLLA/PCL polymer blends compared to pure PLLA has been shown previously. To use numerical simulations in the design process of new components composed of the PLLA/PCL blend, a constitutive model for the material has to be established. In this work, a constitutive model for a PLLA/PCL polymer blend is established from the results of compressive tests at high and low strain rates at three different temperatures, including the body temperature. Finite element simulations of the split Hopkinson pressure bar test using the established constitutive model are carried out under the same condition as the experiments. During the experiments, the changes in the diameter and thickness of the specimens are captured by a high-speed video camera. The accuracy of the numerical model is tested by comparing the simulation results, such as the stress, strain, thickness and diameter histories of the specimens, with those measured in the experiments. The numerical model is also validated against an impact test of non-homogenous strains and strain rates. The results of this study provide a validated numerical model for a PLLA/PCL polymer blend at strain rates of up to 1800s(-1) in the temperature range between 22°C and 50°C.
Copyright © 2015 Elsevier Ltd. All rights reserved.
This research focused on using a block copolymer of poly(ethylene glycol) and poly(propylene glycol) as a new type of compatibilizer in poly(lactic acid)/polycaprolactone (PLA/PCL) blends. The blends were prepared at 80/20 by a melt blending method, and concentrations of the block copolymer were varied from 0-10 phr. The resultant products were characterized in terms of morphology, mechanical, and thermal properties. It was found that the compatibilized blends exhibited a significant enhancement in tensile strain at break compared to that of the neat PLA/PCL blend, in which the highest strain was obtained at 7.5 phr of block copolymer. Tensile stress of the blends was however declined slightly. (C) 2013 The Authors. Published by Elsevier B.V.
In this study, the in-vitro release of proteins from novel, biodegradable phase-separated poly(ε-caprolactone-PEG)-block-poly(ε-caprolactone), [PCL-PEG]-b-[PCL]) multiblock copolymers with different block ratios and with a low melting temperature (49 - 55 ˚C), was studied. The effect of block ratio and PEG content of the polymers (i.e. 22.5, 37.5 and 52.5 wt%) as well as the effect of protein molecular weight (1.2, 5.8, 14, 29 and 66 kDa being goserelin, insulin, lysozyme, carbonic anhydrase and albumin, respectively) on protein release was investigated. Proteins were spray-dried with inulin as stabilizer to obtain a powder of uniform particle size. Spray-dried inulin-stabilized proteins were incorporated into polymeric implants by hot melt extrusion. All incorporated proteins fully preserved their structural integrity as determined after extraction of these proteins from the polymeric implants. In general, it was found that the release rate of the protein increased with decreasing molecular weight of the protein and with increasing the PEG content of the polymer. Swelling and degradation rate of the copolymer increased with increasing PEG content. Hence, release of proteins of various molecular weights from [PCL-PEG]-b-[PCL] multi-block copolymers can be tailored by varying the PEG content of the polymer.
All the above biodegradable polymeric biomaterials could be generally divided into eight groups based on their chemical origin: (1) biodegradable linear aliphatic polyesters (e.g., polyglycolide, polylactide, polycaprolactone, polyhydroxybutyrate) and their copolymers within the aliphatic polyester family like poly(glycolide-L-lactide) copolymer and poly(glycolide-ε-caprolactone) copolymer; (2) biodegradable copolymers between linear aliphatic polyesters in group 1 and monomers other than linear aliphatic polyesters like poly(glycolide-trimethylene carbonate) copolymer, poly(L-lactic acid-L-lysine) copolymer, Tyrosine-based polyarylates or polyiminocarbonates or polycarbonates, poly(D, L-lactide-urethane), and poly(ester-amide); (3) polyanhydrides; (4) poly(orthoesters); (5) Poly(ester-ethers) like polyp-dioxanone; (6) biodegradable polysaccharides like hyaluronic acid, chitin and chitson; (7) polyamino acids like poly-L-glutamic acid and poly-L-lysine; (8) inorganic biodegradable polymers like polyphosphazene and poly[ bis (carboxylatophenoxy)phosphazene] which have a nitrogen-phosphorus backbone instead of ester linkage. Recently, there is a new approach of making new biodegradable polymers through melt-blending of highly accepted biodegradable polymers like those of glycolide and lactide base [Shalaby, 1994].
In an age of increasing societal concerns for an environmentally conscious method of disposing end-use materials, poly(lactic acid)[PLA] offers a viable means to potentially alleviate the repercussions that accompany this complex issue. With biocompatible degradation by-products and physical properties that rival those of polyethylene, polystyrene and polyvinyl chloride, PLA appears to be an attractive alternative to these high-volume commodity thermoplastics from a somewhat superficial perspective.1 However, with its relatively high cost, PLA does not reside in the same marketability category as the aforementioned commodities. A possible resolution to this problem of economics stems from the origin of its lactic acid(LA) building blocks; that is, LA is produced from fermentation of naturally abundant carbohydrates.2 In any event, prior to addressing the ever-present question of cost, the fact that PLA is deficient in certain areas of performance must not be overlooked. With a glass transition temperature(~55–65°C) that resides in a precarious regime if considering biodegradable, consumer product applications, less than adequate thermal and hydrolytic stability, and toughness that is highly dependent upon stereoregularity, it is obvious that much attention must be given to these limitations.
In this study, the in-vitro release of proteins from novel, biodegradable phase-separated poly(ε-caprolactone-PEG)-block-poly(ε-caprolactone), [PCL-PEG]-b-[PCL]) multiblock copolymers with different block ratios and with a low melting temperature (49 - 55 ˚C), was studied. The effect of block ratio and PEG content of the polymers (i.e. 22.5, 37.5 and 52.5 wt%) as well as the effect of protein molecular weight (1.2, 5.8, 14, 29 and 66 kDa being goserelin, insulin, lysozyme, carbonic anhydrase and albumin, respectively) on protein release was investigated. Proteins were spray-dried with inulin as stabilizer to obtain a powder of uniform particle size. Spray-dried inulin-stabilized proteins were incorporated into polymeric implants by hot melt extrusion. All incorporated proteins fully preserved their structural integrity as determined after extraction of these proteins from the polymeric implants. In general, it was found that the release rate of the protein increased with decreasing molecular weight of the protein and with increasing the PEG content of the polymer. Swelling and degradation rate of the copolymer increased with increasing PEG content. Hence, release of proteins of various molecular weights from [PCL-PEG]-b-[PCL] multi-block copolymers can be tailored by varying the PEG content of the polymer.
The effect of multiple (up to 10 times) injection molding of poly(ε-caprolactone) on its mechanical properties, Charpy impact strength, melt flow rate, phase transition temperature and degradation temperature is presented. It was found that the tensile strength at break, impact strength and degradation temperature slightly decreased, while the melt flow rate steadily increased with raising of the number of the injection molding cycles. Variation of the number of these cycles mostly influenced the crystallization temperature. The melting point, enthalpy of crystallization, enthalpy of melting and crystallinity did not vary with the number of injection moldings. The presented results indicate that poly(ε-caprolactone) technological waste is suitable to be reused as an additive to a neat polymer.
An undercooled polymer melt crystallizes by spherulitic growth. In the isothermal case each spherulite possesses the same and constant growth rate. In a thin polymer foil the growth front of each undistributed growth spherulite is a circle with the nucleus at its centre. The growth lines are the orthogonal trajectories to the growth fronts and are approximately equal to the fibrils. A molecular interpretation of spherulitic growth by branching and constitutional undercooling was given by Keith and Padden [i]. In an earlier study we investigated how one spherulite grows around a spherical inclusion in the polymer melt [2]. In this letter we show how a rectangular obstacle is surrounded by a growing spherulite in an approximately two-dimensional polymer foil. Both follow the same principles of growth.
Poly(ɛ-caprolactone) (PCL) has many favourable attributes for tissue engineering scaffold applications. A major drawback, however, is its slow degradation rate, typically greater than 3 years. In this study PCL was melt blended with a small percentage of poly(aspartic acid-co-lactide) (PAL) and the degradation behaviour was evaluated in phosphate buffer solution (PBS) at 37°C. The addition of PAL was found to significantly enhance the degradation profile of PCL. Subsequent degradation behaviour was investigated in terms of the polymer's mechanical properties, molecular weight (Mw), mass changes and thermal characteristics. The results indicate that the addition of PAL accelerates the degradation of PCL, with 20% mass loss recorded after just 7 months in vitro for samples containing 8wt% PAL. The corresponding pure PCL samples exhibited no mass loss over the same time period. In vitro assessment of PCL and PCL/PAL composites in tissue culture medium in the absence of cells revealed stable pH readings with time. SEM studies of cell/biomaterial interactions demonstrated biocompatibility of C3H10T1/2 cells with PCL and PCL/PAL composites at all concentrations of PAL additive.
High molecular weight di- and triblock copolymers of poly(l-lactide), PLLA, (80wt%) with a crystallizable flexible second component such as poly(ε-caprolactone), PCL, or poly(oxyethylene), PEO, (20wt%) were obtained in nearly quantitative yields by ring opening of l-lactide initiated by PCL or PEO hydroxy terminated macromers. The copolymers were characterized by 1H NMR and FTIR spectroscopy and size exclusion chromatography and showed unimodal and narrow molecular weight distributions. X-ray diffraction measurements revealed high crystallinity (38–56%) of the PLLA blocks and gave no clear evidences of PCL or PEO crystallinity. DMTA and DSC techniques showed a melting behaviour of the copolymers (Tm=174–175°C; ΔHm=19–37J/g) quite similar to that of PLLA. PCL and PLLA segments are immiscible, while PLLA and PEO segments are partially miscible in the amorphous phase. Stress–strain measurements indicated a ductile behaviour of the copolymers, characterized by lower tensile moduli (225–961Pa) and higher elongations at break (25–134%) with respect to PLLA.
Warren's calculation of the line profile for diffraction from random layers depends on the use of an approximation function. This can be. avoided, and expressions found for ( a) the ideal line profile for slow variation of the structure amplitude, and ( b) the variation of the intensity of diffraction as a function of position along the `rod' of high intensity in reciprocal space, in terms of the layer shape and the observed line profile. The ideal line profile is, within a trigonometrical factor,
where S 0(= 2 sin 0/ ) is the perpendicular distance from the origin of the reciprocal lattice to the centre line of the `rod', = (sin ² - sin ² 0)/ sin 0, F is the structure amplitude, and A( t) is the area common to a layer and its `ghost' shifted a distance t parallel to S 0. This expression, evaluated for various layer shapes, gives intensities of diffraction slightly lower than those found by Warren and depending somewhat on the layer shape. In particular, the intensity for large negative volumes of is proportional to | | -3/2 multiplied by the maximum breadth of the layer. If w is measured along the `rod' from the foot of S 0, F( w) F*( w) + F(- w) F*(- w) can be obtained by `unfolding' the observed I( ) by means of a double Fourier transformation. Diffraction by random layers can thus give more information than diffraction by a perfect crystal, as the latter gives FF* only for integral values of the indices.
Microstructure and plastic behavior of poly(lactic acid), PLA, and poly(ε-caprolactone), PCL, are investigated. The injected molded specimens are analyzed as received. Thermomechanical properties are characterized by DSC and DMA and crystalline structure by WAXS. The results show that PLA samples are weakly crystalline (14wt%) and that amorphous phase is glassy at room temperature. The PCL samples exhibit higher crystallinity (53wt%) and contain a rubber-like amorphous phase. Mechanical behavior is investigated by means of novel video-controlled materials testing system specially developed to assess true stress vs. true strain curves and to record the volume changes upon stretching. While tested at 50°C, PLA undergoes extensive plastic deformation with a dramatic yield softening followed by a progressively increasing strain hardening. Volume strain, which characterizes deformation damage, increases steadily over the whole plastic stage until reaching 0.27 for an axial strain of 1, 4. For its part, PCL exhibits at 23°C a much progressive plastic response with a soft yield point, no softening, and moderate strain hardening at large strain. Volume change is delayed until axial strain reaches 0.4. Subsequent damage grows very quickly, eventually reaching 0.2 for an ultimate strain of 1, 3. Results are discussed on the basis of microscopic damage mechanisms observed in the stretched state.
Copolymers of ε-caprolactone and L-lactide (ε-CL/L-LA) and ε-caprolactone and DL-lactide (ε-CL/DL-LA) were synthesized with compositions 80/20, 60/40, and 40/60 (wt % in feed). The polymerization temperature was 140°C and Sn(II)octoate was used as a catalyst. The effect of the comonomer ratio on the thermal and mechanical properties of the copolymers was investigated by size-exclusion chromatography (SEC), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) spectrometry, and tensile testing. The copolymers differed widely in their physical characteristics, ranging from weak elastomers to tougher thermoplastics according to the ratio of ε-CL and LA in the copolymerization. Poly(L-lactide) (PLLA), poly(DL-lactide) (PDLLA), and poly(ε-caprolactone) (PCL) homopolymers were studied as references. The tensile modulus and tensile strength were much higher for PLLA, PDLLA, and PCL homopolymers than for the copolymers. The maximum strain was very low for PLLA and PDLLA, whereas the copolymers and PCL exhibited large elongation. © 1996 John Wiley & Sons, Inc.
The improvement of the brittle behavior of Polylactic acid (PLA) resin was studied by blending it with Polycaprolactone (PCL) resin. These materials were fabricated into the compressed films and injection moldings. The values of tensile modulus and strength were appropriate, judging from the rule of mixtures. However, the ultimate tensile strain was very small. Dicumyl peroxide (DCP) was added to this blend system to improve its ultimate tensile strain. It was found that the value of ultimate tensile strain peaked at low DCP concentration. The samples at low DCP contents show yield point and ductile behavior under tensile test. The impact strength of the optimum composition was 2.5 times superior to neat PLA, and ductile behavior such as plastic deformation was observed at its fracture surface. It was found that the carbonyl groups of the blend material with DCP were altered by using FTIR spectroscopy. Dynamic mechanical analysis data revealed the dual phase nature of PLA/PCL blend albeit with good interfacial adhesion, and the DCP enhanced the viscous property in PCL phase, which agreed with tensile ductility and impact strength. The mechanical properties of this blend are comparable to those of general purpose HIPS and ABS. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1816–1825, 2006
Three statistical poly(L-lactide-co-ε-caprolactone) (PLCL) copolymers of 70% L-lactide content having different chain microstructures ranging from moderate blocky to random (R=0.47,0.69 and 0.92, respectively) were characterized by DSC, GPC and (1)H and (13)C NMR. The results demonstrate that higher randomness character (R→1) limits the capability of crystallization of LA-unit sequences shifting the melting temperature of the copolymers to lower values and reducing the crystallinity fraction substantially. The effect of different distributions of sequences of PLCL on crystallization and phase behavior was also studied for different storage times at room temperature (21±2°C) by DSC. The mechanical properties were evaluated by tensile tests during aging. The PLCL showing a random character closest to the Bernoullian distribution of sequences (l(LA)=1/CL) was found to exhibit higher strain capability and strain recovery values and is less prone to supramolecular arrangements. However, as a result of aging, L-lactide sequence blocks in the other PLCLs of smaller randomness character tend to crystallize prompting to a double T(g) behavior indicative of the existence of phase separation into two compositionally different amorphous phases. Physical aging leads also to dramatic changes in tensile behavior of the moderate blocky PLCLs that evolved from being an elastomeric to be partly a glassy semicrystalline thermoplastic, and, thus, can eventually condition its potential uses for medical devices.
Polylactide/clay nanocomposites (PLACNs) were prepared by melt intercalation. The intercalated structure of PLACNs was investigated using XRD and TEM. Both the linear and nonlinear rheological properties of PLACNs were measured by parallel plate rheometer. The results reveal that percolation threshold of the PLACNs is about 4 wt%, and the network structure is very sensitive to both the quiescent and the large amplitude oscillatory shear (LAOS) deformation. The stress overshoots in the reverse flow experiments were strongly dependent on the rest time and shear rate but shows a strain-scaling response to the startup of steady shear flow, indicating that the formation of the long-range structure in PLACNs may be the major driving force for the reorganization of the clay network. The thermal behavior of PLACNs was also characterized. However, the results show that with the addition of clay, the thermal stability of PLACNs decreases in contrast to that of pure PLA.
This study investigated the in vitro release of a model API (Nalidixic Acid) from a PCL bulk extrudate and determined how the extent and rate of drug release are affected by the addition of a pore former (PEG) and of a copolymer (PLLA) within the polymer matrix. Drug release and dissolution is a mass transport operation and therefore can rely on both molecular and bulk diffusion. Typical drug delivery systems are made up of three components; a matrix structure (which does not diffuse and hence, its diffusion coefficient is zero), solution (coming in from the external environment and moving inside the matrix structure) and drug (that usually diffuses from the inner matrix into the external release environment). The release from blends produced by both crash cooling and controlled cooling were considered, alongside those processed via both Single and Twin Screw Extrusion. From analysis of the extrusion process it was found that the polymer crystal size was smaller in blends prepared using a 100 °C/min cooling rate than those prepared using a 30 °C/min cooling rate. Furthermore, the solubility of NA in PCL was improved by a factor of 2 by increasing cooling rate which was attributed to higher percentage of amorphous regions. Moreover, a higher degree of NA release was observed in the faster cooling rate due to the increased solubility. The experimental kinetic drug release data were modelled using a number of simple approaches, and it was found that the Kosmeyer–Peppas model was best at describing the experimental data, with r2 ≥ 0.993. Finally, the hydrolytic degradation of the extrudates at 37 °C (under static aqueous conditions over the period of 6 months) was also analysed to determine degradation rates.
In this work biodegradable blends of poly(d,l-lactide) and poly(ε-caprolactone) were studied. The weight fraction of poly(ε-caprolactone) was varied between 0 and 100%. The originally immiscible blends were compatibilized with l-lysine-diisocyanate and l-lysine-triisocyanate, respectively, to increase the fracture toughness of materials and maintain their biocompatibility. The blend morphology was characterized by scanning electron microscopy and differential scanning calorimetry. The fracture properties of blends were analyzed by the essential work of fracture method.
During the resorbable-polymer-boom of the 1970s and 1980s, polycaprolactone (PCL) was used in the biomaterials field and a number of drug-delivery devices. Its popularity was soon superseded by faster resorbable polymers which had fewer perceived disadvantages associated with long term degradation (up to 3-4 years) and intracellular resorption pathways; consequently, PCL was almost forgotten for most of two decades. Recently, a resurgence of interest has propelled PCL back into the biomaterials-arena. The superior rheological and viscoelastic properties over many of its aliphatic polyester counterparts renders PCL easy to manufacture and manipulate into a large range of implants and devices. Coupled with relatively inexpensive production routes and FDA approval, this provides a promising platform for the production of longer-term degradable implants which may be manipulated physically, chemically and biologically to possess tailorable degradation kinetics to suit a specific anatomical site. This review will discuss the application of PCL as a biomaterial over the last two decades focusing on the advantages which have propagated its return into the spotlight with a particular focus on medical devices, drug delivery and tissue engineering.
Poly(epsilon-caprolactone)-poly(ethylene glycol) (PECL) copolymers were synthesized from polyethylene glycol (PEG) and epsilon-caprolactone (epsilon-CL) using stannous octoate as catalyst at 160 degrees C by bulk polymerization. The effect of the molecular weight of PEG and the copolymer ratio on the properties of the copolymers was investigated by (1)H-NMR, IR, DSC and GPC. PCL and PECL microspheres containing human serum albumin were elaborated by solvent extraction method based on the formation of double w/o/w emulsion. Microspheres were characterized in terms of morphology, size, loading efficiency, and the efficiency of microspheres formation. The results show that the microspheres prepared from PECL-10 and PECL-15 copolymers achieved the highest loading efficiency (about 50%) among all copolymers. These results indicate that the properties of copolymers could be tailored by adjusting polymer composition. It is suggested that these matrix polymers may be optimized as carriers in the protein (antigen) delivery system for different purposes.
Biodegradable polymers such as poly(lactide) (PLA) and poly(epsilon-caprolactone) (PCL) are increasingly used in biomedical applications as temporary implants. However, melt processing of these materials in particular of PLA is difficult due to the temperature sensitivity. Within this study, PLA and PCL were injection molded conventionally and by using the process shear controled orientation in injection molding (SCORIM) in order to investigate the effect of processing parameters on the physical properties of the moldings. Therefore, flexural testing, differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), molecular weight (MW) and orientation measurements were performed. PLA showed high sensitivity to melt temperature. In the case of amorphous poly(DL-lactide), the molecular weight and subsequently the ductility is substantially reduced by processing at higher melt temperatures. In the case of crystallizable poly(L-lactide), higher melt temperatures and shear induced by the SCORIM process resulted in enhanced crystallinity, which compromised the mechanical properties. Generally, SCORIM processing improved the mechanical properties, in particular the ductility, by orientating the molecular structure. PCL was shown to be less sensitive to shear and temperature than PLA. Stress at yield and stiffness are more improved by SCORIM processing. However, the processing temperature in combination with the grade used proved to be influential for the mechanical properties of resulting moldings.
The objective of this work was to study the effect of blending chitosan with poly(epsilon-caprolactone) (PCL) on their biomechanical properties. After testing the effect of molecular weight (MW), temperature, and humidity on the tensile properties in dry, wet at 25 degrees C and wet at 37 degrees C conditions, chitosan with a MW>310 kD was selected for use in the blend. Homogeneous blends of 25%, 50% and 75% PCL compositions were formed by dissolving chitosan and 80 kD PCL in a common solvent of approximately 77% aqueous acetic acid. Taking advantage of the low melting point of PCL, blend membranes were processed at 25, 37, 55 degrees C water bath or 55 degrees C oven into films. Also, membranes were solvent annealed using chloroform vapors. Tensile properties were analyzed in wet conditions at 25 degrees C. Support for cell viability and distribution of cytoskeletal actin were analyzed by in vitro cell culture of mouse embryonic fibroblasts (MEFs). Differential scanning calorimetry studies indicated the miscibility of the two components when approximated using Nishi-Wang equation. Drying the films at 55 degrees C in an oven formed membranes without separation of two phases. However, the analyzed tensile properties showed no significant alterations relative to chitosan. On the contrary, significant improvements were observed after solvent annealing. Interestingly, increased viability and redistribution of actin fibers was observed on blends formed with 50% PCL and 75% PCL relative to individual polymers. In summary, 50:50 blends when processed at 55 degrees C in an oven showed significant improvement in mechanical properties as well as support for cellular activity relative to chitosan.
A series of blends of the biodegradable polymers poly(D,L-lactic acid) and poly( epsilon -caprolactone) were prepared by varying mass fraction across the range of compositions. Tensile testing was performed at room temperature using an extensometer and the elastic modulus was calculated for each blend. The blends were also tested to failure, and the strain-at-failure and yield stress recorded. While the blend has been shown to have a lower critical solution temperature, the mechanical properties were insensitive to the annealing conditions. Scanning electron microscopy was used to characterize the blend microstructure and poor adhesion was observed at the interface between blend components. Differential scanning calorimetry was performed but the results were somewhat variable, indicating this blend may have complex phase behavior that depends sensitively on the method of preparation. However, nuclear magnetic resonance data indicate the two components are phase separated. A percolation model is used to explain the observed mechanical data and the results are consistent with the predictions of the Kerner-Uemura-Takayangi model. The results of these experiments demonstrate the utility of polymer blending in tuning material properties.
Thermal Conductivity 21
- C J Cremers
- H A Fine
Cremers, C.J., Fine, H.A. 1991. Thermal Conductivity 21, 1st Edition. Springer, London.