Langmuir 1995,11, 3921-3927
3921
Relating the Phase Morphology of a Biodegradable Polymer Blend to Erosion Kinetics Using Simultaneous in Situ Atomic Force Microscopy and Surface Plasmon Resonance Analysis Kevin M. Shakesheff,?Xinyong Chen: Mart C. Davies,",?Avi Domb,§ Clive J. Roberts,*,?Saul J. B. Tendler,*,iy"and Phil M. Williams? Laboratory of Biophysics and Surface Analysis, Department of Pharmaceutical Sciences, The University of Nottingham, Nottingham NG7 2RD, U.K., Department of Applied Physics, Chongqing University, Siehuan 630044, China, and The Hebrew University of Jerusalem, School of Pharmacy, Jerusalem, Israel 91 120 Received March 27, 1995. In Final Form: June 5, 1995@ The blending of established biodegradable polymers,offers the potential to fabricate new polymeric materials whose erosion kinetics can be modified by varying the composition of the blend. However, the immiscibility of most polymer blends complicates the erosion kinetics because of the influence of phase morphology on degradation. In this paper, we describe how the simultaneous acquisition of atomic force microscopy (AFM) and surface plasmon resonance (SPR)data can be used to interpret the effect of phase morphology on erosion. We have analyzed the degradationof thin films of blends of poly(sebacicanhydride) (PSA)and pOly(DL-laCtiCacid) (PLA)using a combined AFWSPR instrument, which enables the dynamic changes in surface morphology resulting from polymer degradation to be related to the SPR recorded kinetics of film erosion. This analysis has demonstrated three stages in the erosion of the films at pH 11, with the rapid loss of PSA dominating the initial stage of erosion, the slow loss of PLA detected in the final stage, and an intermediate stage displaying an extended transitional period during which the rate of erosion has an intermediate value. The effect of blend composition on phase morphology and hence the relative importance of these three stages during erosion are explored.
Introduction In the design of new polymeric materials it is an attractive strategy to combine two or more existing polymers to form a b1end.l Ideally, the blend will possess the desirable properties of each of the constituents. This strategy has been particularly successfblin the production of toughened polymers in which a brittle polymer (e.g. high impact polystyrene) is mixed with a ductile polymer (e.g. poly(2,6-dimethyl-l,4-phenyl oxide)) to give a blend which combines the high modulus of the brittle polymer with the shear yielding ability of the ductile polymer.2 Recently, blending techniques have been applied in the design of biodegradable material^.^ Our interest in these materials stems from their application in surface erosion controlled drug delivery systems. The schematic diagram in Figure 1 demonstrates the mechanism of action of these delivery systems. The drug is dispersed within a matrix of the biodegradable polymer and this matrix is then introduced into the patient. Within the aqueous environment of the body, the pure drug would normally be able to dissolve and hence become available for therapeutic action; however, this dissolution is prevented by the hydrophobic polymeric material. The release of drug from these devices can occur only as a result of the hydrolysis of the polymer at the interface with the biological system. Therefore, the release of the drug, and hence its thera-
(a) Prior to drug release Aqueous environment Biodegradable polymer
b g
Polymedwaterinterface
(b) During drug release Aqueous environment Eroded polymer surface 0
0
-Released
t The University of Nottingham. Chongqing University. The Hebrew University of Jerusalem. Abstract published inAdvunceACSAbstructs, August 15,1995. (1) Paul, D. R., Newman, S., Eds. In Polymer Blends; Academic Press: New York, 1979; Vol. 2. (2)Paul, D. R.; Barlow, J. N.; Keskkula, H. In Encyclopedia of Polymers Science and Engineering;Krowschwitz,J. I., Ed.; John Wiley & Sons: New York, 1988. (3) Domb, A. J. J. Polym. Sci.: Part A: Polym. Chem. 1993,31,19731981.
drug
availablefor therapeutic action
@
Figure 1. Schematicdiagram of the controlled release of drug
using a surface eroding polymer matrix. peutic activity, is directly linked to the surface erosion of the polymer. Clearly, the most important parameter in
0743-7463/95/2411-3921$09.00/00 1995 American Chemical Society
3922 Langmuir, Vol. 11, No. 10, 1995
the kinetics of drug release from these systems is the degradation of the polymer at the polymerlwater interface.4 Considerable success has been achieved with surface eroding delivery systems using matrices containing a single component p ~ l y m e r . ~For . ~ such systems, the kinetics of degradation at the polymerlwater interface are largely determined by the chemical structure of the polymer backbone, which in turn determines the hydrolytic susceptibility. However, this can generate an inflexible delivery system, because there are only a limited number of strategies with which to change the kinetics of drug release. These strategies include changing the shape of the delivery system and hence the polymer surface area, o r synthesizing a new polymer with a different backbone s t r ~ c t u r e .A~ much more flexible drug delivery device can be designed if two biodegradable polymers, with very different degradation rates, form the matrix. It may then be possible to vary the kinetics of surface degradation by changing the relative amounts of each polymer in the blend. The concept of controlling degradation rates by varying polymer blend composition is complicated by the immiscibility of most pairs of polymers.' This immiscibility arises from the low entropy increase which results from mixing long polymer chains with each other. As a consequenceof this, the Gibbs free energy change of mixing is generally positive favoring polymer phase separation. When phase separation occurs, the degradation kinetics of the matrix will be highly influenced by the morphology of the two-phase system. Therefore, there is a requirement when designing polymer blend matrices to characterize the phase morphology in order to understand the degradation profile of the resulting devices. This phase morphology characterization has been performed by a number of different microscopy techn i q u e ~ Scanning . ~ ~ ~ electron microscopy (SEM)has been employed to study fracturelo and thin film'' surfaces of polymer blends. These studies require the fracture surface to be coated with a thin metallic film and it is generally difficult to identify the different phases. One approach to achieve differentiation is to remove one of the phases by solvent extraction.1° This has been applied to study, for example, the mixing of hydroxyl-functionalized polystyrene (PSI and poly(ethy1acetate) (PEA).I0 Transmission electron microscopy (TEM) has proved valuable in the study of thin sections of blend.g Again, there is a problem in differentiating the polymer phases. This can be overcome, for some polymers, by preferentially staining one of the polymer phases using an electron dense dye, such as osmium tetraoxide.'* There have also been promising studies performed using laser confocal fluorescence microscopy (LCFM)13on poly(methy1methacrylate) (PMMA)and PS blends. The PMMA component of the blend was labeled with a fluorescent dye which enabled the phase morphology to be visualized at the surface and to depths of 6 pm. (4) Langer, R. Science 1990, 249, 1527. ( 5 ) Brem, H. Biomaterials 1990, 11, 699. (6) Heller, J. J . Controlled Release 1985, 2, 167. (7) Gopferich, A.; Langer, R. J . Polym. Sci., Part A: Polym. Chem. 1993,31, 2445. (8) Woodward, A. E.Atlas ofPolymerMorphology;Hanser Publishers, Oxford University Press, 1989; Chapter 9. (9) Hess, W. M.; Herd, C. R.; Vegvari, P. C. Rubber Chem. Technol. 1993, 66, 329-375. (10)Taylor-Smith,R:E.; Register, R. A. J . Polym. Sci., Part B: Polym. Phys. 1994,32, 2105. (11) Shabana, H. M.; Guo, W.; Olley, R. H.; Bassett, D. C. Polymer 1993, 34, 1313. (12) Kato, K. J . Electron Microsc. J p n . 1965, 14, 219. (13) Li, L.; Sosnowski, S.; Chaffey, C. E.; Balke, S. T.; Winnik, M. A. Langmuir 1994, 10, 2495.
Shakesheff et al.
Recently, there have been a number of reports on the use of scanning probe microscopy in the study of phase morphology in blend materials.l4-I7 Our group has described the use of atomic force microscopy (AFM) to study the morphology of immiscible blends of poly(sebacic anhydride) (PSA) and poly(D,L-lactic acid) (PLA).14 By employing in situ AFM techniques, it has been possible to visualize the morphological changes that occur when thin films of this blend are exposed to an alkaline aqueous environment. These studies showed that the PSA is rapidly removed from the film via surface erosion leaving the surface topography of the film dominated by the PLA morphology, due to the higher susceptibility of PSA to hydrolysis. There are considerable advantages in using in situ AFM to analyze these blends because in addition to recording the phase morphology of the PSA and PLA it is possible to directly visualize the effect of the morphology on the degradation profile. In this paper, we extend our study of PSAPLA blends using a novel instrument, constructed in our laboratory, which facilitates simultaneous atomic force microscopy and surface plasmon resonance (SPR) analysis.18Jg A schematic diagram of the design of this instrument is shown in Figure 2. The SPR technique is a highly sensitive method of monitoring changes in the thickness of thin films deposited on the silver surface of the SPR sensors.20-26The basic instrumentation required for SPR analysis is displayed in Figure 2. Briefly, a plane polarized laser beam is targeted through a hemicylindrical prism onto the glasslsilver interface of the sensor. If the angle of incidence between the laser and the glass surface is above a critical angle, then total internal reflection occurs and the resultant reflection is detected by an array of photodiodes. There exists an incident angle, termed the SPR angle, at which the laser causes a resonant excitation of the surface electrons (i.e. plasmon) of the silver film on the SPR sensor.26This coupling effect results in a decrease in the laser intensity as measured by the photodiodes. The angle at which coupling occurs is highly dependent on the dielectric properties of the material in contact with the silver surface.26 If a thin film of a material absorbs to the silver, then the SPR angle is shifted to a higher value. The magnitude of shift of the SPR angle has been shown to be dependent on the thickness of the film.23 Therefore, SPR analysis provides a method of following the changes in thickness of a biodegradable polymer film in real time, as a result of the surface degradation. (14) Shakesheff, K. M.; Davies, M. C.; Roberts, C. J.; Tendler, S. J. B.; Shard, A. G.; Domb, A. Langmuir 1994, 10, 4417. (15) Overney, R. M.; Meyer, E.; Frommer, J.; Brodbeck, D.; Liithi, R.; Howald, L.; Giintherodt, H.-J.; Fujihira, M.; Takano, H.; Gotoh, Y. Nature 1992. 359. 133. (16) Motomatsu, M.; Nie, H.-Y.; Mizutani, W.; Tokomoto, H. J p n . J . Appl. Phys. 1994,33, 3775. (17) Dikland, H. G.; Sheiko, S. S.;vander Does, L.; Moller, M.; Bantjes, A. Polymer 1993,8, 1773. (18) Chen, X. C.; Davies, M. C.; Roberts, C. J.; Shakesheff, K. M.; Tendler, S. J . B.; Williams, P. M. Submitted for publication. (19)Chen, X.; Shakesheff, K. M.; Davies, M. C.; Heller, J.; Roberts, C. J.;Tendler, S. J. B.; Williams, P. M. J . Phvs. Chem. 1995.99.11537. (20)Davies, J. Nanobiology 1994, 3, 5. (21)de Bruijn, H. E.; Altenburg, B. S. F.; Kooyman, R. P. H.; Greve, J. Opt. Commun. 1991, 82, 425. (22)Matsubara, K.; Kawata, S.; Minami, S. Appl. Spectrosc. 1988, 42, 1375. (23) Pockrand, I. Surfi Sci. 1978, 72, 577. (24) Kretschmann, E. Z. Phys. 1971, 241, 313. (25) Davies, J.;Roberts, C. J.;Dawkes, A. C.; Sefton, J . ; Edwards, J. C.; Glasbey, T. 0.; Haymes, A. G.; Davies, M. C.; Jackson, D. E.; Lomas, M.; Shakesheff, K. M.; Tendler, S. J. B.; Wilkins, M. J.;Williams, P. M. Langmuir 1994, 10, 2654. (26) Raether, H. Surface plasma oscillations. In Physics of Thin Films; Hass, G., Francombe, M. H., Hoffman, R. W., Eds.; Academic Press: New York, 1997; Vol. 9.
Langmuir, Vol. 11, No. 10, 1995 3923
Polymer Blend Morphology AFM later
(a) PSA
AFM probe. and cantilever
/
(b) PLA
AFMlSPR compartment
p Thin silver film
CH-C-O 3 :
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i ,
\\
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,
.
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Figure 2. Schematic representation of the AF'WSPR instrument. The SPR component has a Kretschmann ~onfiguration,2~ in which a laser is shone onto the underside of the sensor and reflected onto a photodiode array. The free standing AFM component is placed on top of the SPR unit, with a silicon O-ring sealing the AF'WSPR compartment.
The combination of AFM and SPR is possible due to the geometric and analytical complementarity of the two techniques. The AFM records topographical information using instrumentation that is positioned above the SPR sensor, while the SPR monitors changes in film thickness using instrumentation positioned exclusively below the sensor. We have previously described the use of this combined instrument to study the degradation of a single component poly(ortho ester) film.lg These studies have demonstrated the synergistic nature of the information obtained. The AFM recorded changes in polymer film structure could clearly be related to changes in the rate of thinning of the film, as monitored by the SPR. The combined instrument also proved to be a highly sensitive method of measuring the effect of pH on the kinetics of hydrolysis of the poly(orth0 ester). In the present study, we analyze the influence of polymer blend composition and morphology on degradation. Initially we describe the characterization of the degradation of the two polymers in. single component films. Then blended films with compositions of 70% PSA30% PLA, 50% PSA50% PLA, and 30%PSA:70% PLA were analyzed.
(Polysciences, Inc., Warrington, U.K.). Thin film preparation was performed as for PSA. To prepare blended films of PSA and PLA, the chloroform solutions of the two polymers were mixed in the desired proportions and spin casting was performed as before. The chemical structure of the two polymers is shown in Figure 3. Combined AFWSPR Analysis. The combined AFWSPR instrument was constructed using modified commercial instruments. The AFM component is based on a Topometrix Explorer (J.K. Instruments Ltd., Saffron Walden, Essex, U.K.) which was altered to incorporate inlet and outlet ports in a 3 pm scanner tube. AFM images were obtained in contact mode using Si3N4 probes on triangular cantilevers. The scan rate was set during imaging to 5 Hz giving a total image acquisition time of approximately 2 min. AFM images in this paper are displayed in shaded view, with the topography shown as if illuminated at a shallow angle to the normal from the left-hand side. The SPR instrument (Kodak Clinical Diagnostics,Ltd., Buckinghamshire, U.K.) was modified by isolating the optical unit from the control unit to minimize vibrational effects on the SPR sensor. The instrument uses a laser with a wavelength of 780 nm. The SPR sensors consist of glass slides with thin films of silver (approximately 50 nm thick) deposited on one side. Following the preparation of a polymer film on the SPR sensor silver coated side, the sensor was placed on the hemicylindrical prism of the SPR component,with the uncoated side of the sensor index matched with the prism using microscope immersion oil (Resolve, Stephens Scientific, Riverdale). The AFM unit was then positioned on top of the sample with a siliconerubber O-ring used to create a sealed compartment between the SPR sensor surface and the AFM (referred to as the AFWSPR compartment). Deionized water was then pumped into the AFWSPR compartment using a syringe driver. This created the aqueous environment in which AFM and SPR data could be simultaneously acquired. After 30 min, the liquid inside the syringe was changed to pH 11 using a KCVNaOH buffer.28 This buffer was pumped into the AFWSPR compartment a t a rate of 1 p u s . When the 1 mL volume of buffer contained in the syringe was depleted, it was immediately replenished and pumping restarted. During the experiments, the SPR unit measured the angle of minimum reflectivity, as recorded by the photodiode array. This minimum was plotted against time. Periodically, AFM images were recorded. It was found that the pumping of the buffer caused some deterioration in the AFM data, and therefore, for the 1 min period of image acquisition the syringe driver was paused.
Results and Discussion Analysis of Single Component Films. The two polymers used to form the immiscible blends are known to display very different hydrolyticsusceptibilitieswithin alkaline conditions. As a first stage of the combined A F M / Materials and Methods SPR analysis we established the effect of these suscepPreparation of Polymer Films. PSA (M,25 000) was tibilities on degradation within a pH 11environment of synthesized by melt polycondensation as described p r e v i o u ~ l y . ~ ~ polymer films containing the individual polymers alone. Preparation of thin films consisting of only PSA was performed The AFM and SPR data recorded during the degradation at room temperature by dissolving 10 mg of polymer in 1 mL of of a PSA film is displayed in Figure 4. The four AFM chloroform and then spin casting 50 pL of the resulting solution images show the topographical changes occurring to a 3 onto the silver surface of the SPR sensor at approximately 1500 pm x 3 pm area of the sample. On the simultaneously rpm. The PLA material (M,50 000) was used as purchased (27) Domb, A. J.; Langer, R. J. Polym. Sci., Part A: Polym. Chem. 1991,42, 1597.
(28) CRC Handbook of Chemistry and Physics, 74th ed.; Lide, D. R., Ed.; CRC Press, Inc.: Boca Raton, 1993; Chapter 5.
3924 Langmuir, Vol. 11, No. 10,1995
4b 4c 4d
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Shakesheffet al.
4 0
I
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30 40 Time (min)
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Figure 4. Simultaneously acquired AFM/SPR data of the erosion of a single component PSA film in a pH 11 aqueous environment: (top) 3 pm x 3 pm AFM images of the film topography during erosion; (bottom) the change in SPR angle with time.
acquired SPR data, the time at which each AFM image was recorded is indicated by a labeled arrow. Initially, we characterized the PSA film before degradation with the AFWSPR compartment filled with pH 7 water. The AFM image displayed in micrograph a of Figure 4 shows the fibrous morphology of the PSA film at t = 0 min with fibers possessing diameters of between 50 and 300 nm. The formation of a fibrous morphology is characteristic of semicrystalline polymers and has previously been documented for PSA.29 The presence of the PSA film on the SPR sensor caused the SPR angle to shift from 64.9" for the uncoated silver to a value of 68.4". The degradation experiment was started by initiating the pumping of the pH 11 buffer into the AFWSPR compartment. For a period of approximately 10 min after the start of pumping, the SPR angle was unchanged. This time period corresponded to the time required for the buffer to travel from the syringe to the AFWSPR compartment and displace the initial water in the AFWSPR compartment. This was observed for all of the SPR data presented in this paper; however, the absolute length of time varied (29) Mathiowitz, E.; Jacob, J.; Pekarek, K.; Chickering, D. Macromolecules 1993,26,6756.
between 5 and 10 min depending on the volume of buffer in the syringe. As the buffer displaced the water, there is a slight increase in the SPR angle from 68.4" to 68.7", due to the detection of an increase in the ionic concentration. At t = 11 min the effect of polymer degradation became dominant and the SPR angle decreased rapidly at a rate of 0.163 deg min-l for a period of 10min. During this 10-min period, the AFM image in micrograph b of Figure 4 was recorded. This image displays the start of the erosion of the film and, in particular, the breakdown of the fibrous surface structure. The next stage in the SPR data showed a reduction in the rate of decrease of the SPR angle until, after 65 min of the experiment, the SPR angle maintained a constant value of 64.2", a value which would be expected for the silver film of an uncoated SPR sensor. AFM images recorded during this period (micrographsc and d of Figure 4(i)) show the loss of the PSA film from the SPR sensor. The exposure of the silver surface with the characteristic particulate structurelg can be seen in these images. In the analysis of the degradation of the PSA film, the AFWSPR instrument has recorded the rapid loss of the film as a result of hydrolysis. The initial rapid rate sf SPR angle decrease occurs when the polymer film completely covers the SPR sensor surface. Then, as this complete coverage is lost, the rate of erosion slows due to the decrease in the polymer surface area and, hence, the reduction of the number of sites available for hydrolytic attack. One problem that has to be addressed when analyzing simultaneously acquired AFWSPR data is the differences in the time at which the complete loss of the polymer film is recorded. In the example shown in Figure 4, the AFM data appear to show complete film removal after 24 min, while the SPR angle continues to fall after this period. The explanation of this lies in the difference in the sample areas analyzed by the two techniques. The AFM analyses a surface area of the sample of 9 pm2 compared to an estimated area of 5000 pm2 analyzed by SPR.30 Therefore, the SPR data will tend to average out any heterogeneity in the rate of film removal across the sample surface. This explanation is supported by many other degradation experiments we have performed with the AFWSPR instrument, in which the surface changes recorded by AFM have been found to occur a t both quicker and slower rates than the changes recorded by SPR. The analysis of the degradation of the single component PLA film emphasiszed the differences in the rates of hydrolysis of PSA and PLA. The AFM and SPR data for PLA are displayed in Figure 5. The AFM recorded surface morphology of the PLA film displays the smooth nature of the surface at this scale that is typical of a spun cast film of a low crystallinity polymer. The SPR angle recorded for this film was 70.1". The contrast between the rates of degradation of the PLA and the PSA is apparent. For the PIA degradation the rate of SPR shift was found to be 0.001 deg min-l, and after 160 min of degradation the SPR angle was lowered by only 0.22" in total. The AFM data recorded simultaneously over this period of time demonstrated no changes in surface morphology. Analysis.of PSA/PLA Blend. As a first step in the characterization of the degradation of these PSA/PLA blends, we will consider the effect of the blend composition on the AFM recorded surface morphology. The AFM images in Figure 6a-c show the surface morphology of the 70:30, 5050, and 30:70 PSA/pLA blends prior to degradation, respectively. All three images show the (30) Davies, J.; Allen, A.; Bunus, Y.; Bruce, I.; Heaney, P. J.; Hemming, F. A.; Nunnerly, C. S.; Skelton, L. In Surface Properties of Biomaterials;West, R., Batts, G., Eds.; Butterworth-HeinemannLtd.: Oxford, 1993.
Polymer Blend Morphology
Langmuir, Vol. 11, No. 10, 1995 3925
70 k-
t
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Figure 5. AF'WSPR analysis of the erosion of a single component PLA film: (top) 3 pm x 3 p m AF'M images of the film topography at t = 0 min; (bottom)SPR data recorded during erosion.
Figure 6. 3 pm x 3 pm AFM images of the effect of PSAPLA blend composition on surface morphology. Areas marked i are island structures which decrease in size as the PSA percentage decreases in the blend. Areas marked n are examples of the network structure.
phase separated morphologies of these films, with a continuous network of one component (marked n) and isolated islands of the other component (marked i). As the proportion of PSA in the blend is decreased, the size of the isolated islands shrinks, indicating that the PSA forms the islands in the network of the PLA. We now consider the combined AFWSPR data recorded for the degradation of the 70:30 PSA/PLA film. The
dynamic surface topography changes occurring during degradation are displayed in the eight AFM images in Figure 7(i) and the corresponding shift in the SPR angle with time is plotted in Figure 7(ii) with the times of acquisition of the AFM data again indicated with labeled arrows. After the initial lag phase, there is a period of rapid decrease of the SPR angle. The decrease reaches a maximum rate of 0.170 deg min-l between t = 15 and 37 min and the actual SPR angle falls by 3.32'. This rate is very similar to the rate recorded for the single component PSA film. During this period, the AFM images in micrographsb-d of Figure 7 were recorded. These images record the loss of polymeric material from the islands, i.e. the removal of PSA material. This removal results in the formation of pits which increase the prominence of the PLA network as highlighted by the cross sections displayed in Figure 7. In the AFM image in micrograph d of Figure 7, the topography of the underlying silver surface of the SPR sensor is becoming apparent on those areas not covered by the PLA network. Clearly, both the AFM and SPR data indicate the removal of PSA material in the first 40 min of exposure to the pH 11environment. After the initial rapid rate of decrease of the SPR angle, there is a deceleration period. This deceleration is expected due to the decreased surface area of the PSA available for degradation as the SPR sensor surface is exposed. However, the rate of SPR angle shift does not fall to zero as was observed for the single component PSA film (Figure 4). Instead, over a period of 140min, the rate of shift slowly falls from 0.04 deg min-l a t t = 40 min to 0.001 deg min-l a t t = 180min. The AFM images recorded during this period are displayed in micrographs e-h of Figure 7 (it should be noted that the image area analyzed in micrographs e-h of Figure 7 has shifted slightly from the area in micrographs a-d of Figure 7 due to a readjustment of the AFM cantilever setup a t t = 40 min). The topographs show small changes occurring to the network structure as degradation occurs. The most noticeable structural change is a widening of the pits as the polymer network shrinks. However, it is clear that the rate of degradation has slowed considerably compared with the early phase of PSA removal. The interesting aspect of this period of the film degradation is that the AFWSPR data indicate that the hydrolytic removal of polymeric material occurs at a rate which is intermediate to that of removal recorded for the single component films. It appears, therefore, that the blending of these polymers achieves the objective of generating new materials with characteristics moderated by the two components. The mechanismby which this intermediate rate of degradation is achieved has not been elucidated. However, it is possible that PLA is protecting the remaining PSA material. One possible mechanism of this protection is the tendency for the PLA material to preferentially reside at the surface of these blended films. This may result in a surface layer of PLA which masks the degradation of underlying PSA. At the end of this degradation experiment, the rate of SPR angle shift is 0.0005 deg min-l, which is consistent with the degradation of a pure PLA film given the decrease in surface area of a network compared with a complete film. Therefore, from the AFWSPR data we can identify three stages in the degradation of the PSA/PLA (70:30) blend films. Initially, there is a rapid loss of PSA islands. Then there is a long intermediate stage during which film removal occurs slower than the rate expected for PSA and faster than the rate for PLA. Finally, the degradation profile reflects the loss of pure PLA material. The next step in our analysis of these blends was to further explore the nature of this intermediate stage by
Shakesheffet al.
3926 Langmuir, Vol. 11, No. 10, 1995
65
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x 3 pm AFM data recorded during the erosion of a 70:30 PSAPLA blend at pH 11. (top right) SPR data recorded simultaneously with AFM data in (i). (bottom right) Cross sections of the AFM data in a, b, c, and d showing the formation of a pit as a result of the rapid loss of PSA material from the film. The cross sections were recorded from the PSA island directly below the 0 min label in micrograph a.
Figure 7. (left) 3 pm
analyzing films containinghigher proportions of PLA. The AFWSPR data recorded during the degradation of a 30: 70 PSAPLA film is displayed in Figure 8. The AFM images demonstrate a similar general pattern of degradation as observed in the 70:30 PSA/PLA blend, with an initial erosion of the PSA islands which leaves the PLA network structure exposed. The SPR data in Figure 8(ii) show the effect of degradation of the SPR angle over a 250 min time period. Initially, once the pH 11 buffer had displaced the water, there was a period of relatively rapid SPR angle decrease as the PSA material was removed. The maximum rate of SPR angle shift was 0.118 deg min-l, which is lower than the maximal values for both the single
component PSA film and the high PSA composition blend. This may be expected due to the relatively small area of the PSA islands in this film. Over the next 220 min of the experiment, the rate of SPR angle shift underwent a slow deceleration. However, the decelerationwas considerably slower than that recorded for the 70:30 P S W L A blends, and when the experiment was terminated after 250 min, the rate of shift was still 0.004 deg min-l. In summary, as the relative proportion of PLA in the blend increases,the intermediatephase in the degradation of the film is greatly extended. This indicates that the polymer blend performs as designed. The effect of increasing the PLA content is to lengthen the period of
Langmuir, Vol. 11, No. 10, 1995 3927
Polymer Blend Morphology 71 h
$
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Figure 9. SPR data recording the effect of pH 11erosion of a 5050 PSA/PLA blended film on the SPR angle.
8a
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:
;
:
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Figure 8. Simultaneous AFM (3 pm x 3 pm) (top) and SPR (bottom) data recorded during the erosion of a 30:70 PSA/PLA blended film a t pH 11.
time during which the degradation rate occurs at a intermediate value. We also performed AFWSPR analysis on a 5050 PSA/PLA blend. The SPR data are displayed in Figure 9. Again, the pattern of degradation recorded displays the three distinct stages. As expected, the time for each phase and the rate of fall in SPR angle are midway between the values for the 70:30 and 30:70 PSA/PLA films.
Conclusions The use of the combined AFWSPR instrument has provided a new method of studying biodegradable polymer blends which has the advantage of assessing the influence of phase morphology on the erosion kinetics. The data recorded during the degradation of blends of PSA and PLA have identified the contribution of the constituent polymers to the erosion process. Analysis of the single
component films demonstrates the effect of the difference in hydrolytic susceptibility on the erosion kinetics, with the maximum rate of SPR shift recorded to be 100 times greater for PSA than for PLA. When the polymers are blended in thin films, the erosion kinetics can be broadly fitted into three stages, with the loss of PSA islands occurring rapidly in the early period of degradation. This initial removal of PSA results in the surface morphology of the films becoming dominated by a network structure. Then, there is a transitional stage during which the rate of SPR angle shift slowly falls from a rate characteristic of PSA to a rate expected for PLA. During this period, there are,minorchangesoccurring to the network structure and the blend system achieves the aim of producing erosion behavior which lies between the kinetics of the PSA and PLA. In the final stage of erosion, the kinetics become similar to the kinetics expected for a pure PLA film. It is highly encouraging that by increasing the amount of PLA in the blend, it is possible to decrease the extent of film erosion produced by the rapid PSA loss and increase the contribution of the transitional stage. This work provides further evidence of the promise of polymer blends in the design of new materials for biomedical applications. The use of the combined AFW SPR instrument gives a new insight into the importance of polymer blend morphology in determining the kinetics of erosion. The approach of combining the dynamic topographical data from AFM with the kinetics data from SPR can be applied to many other fields of materials research, particularly in the design of biomaterials where dynamic surface changes, such as protein adsorption, determine the suitability and function of polymers.
Acknowledgment. The authors acknowledge the support of the Britemuram programme, the BBSRC Biotechnology Directorate, the EPSRCDTI Nanotechnology LINK programme, Fisons Instruments, Kodak Limited, and Oxford Molecular Group plc. X.C. thanks the State Education Commision of China for funding his sabbattical within the Laboratory of Biophysics and Surface Analysis. LA950237M
