Novel Growth of Biodegradable Thin Films via Matrix Assisted Laser Processing

A.L. Mercado1, J.M. Fitz-Gerald1, R. Johnson2, and J.D. Talton3

1University of Virginia, Dept of Materials Science and Engineering2University of Virginia, Dept of ChemistryCharlottesville, VA 22904-47453Nanotherapeutics Inc, Alachua, FL

ABSTRACT

The ability to controllably deposit polymers onto flat or curved surfaces in a quasi-dryenvironment while retaining native-like structure is of extreme importance to the medical andmicroelectronics communities. Current applications range from protective and conformalcoatings for microelectronics to sustained drug delivery platforms in the pharmaceutical industry.In this research, biodegradable thin films of poly(DL-lactide-co-glycolide) (PLGA), weredeposited onto flat substrates of Si and NaCl using a pulsed excimer laser, (λ= 248 nm) withfluences ranging from 0.1 – 1.0 J/cm2 via matrix assisted pulsed laser evaporation (MAPLE).Results are shown from scanning electron microscopy (SEM) to study morphological featuresand Fourier Transform Infrared Spectroscopy (FTIR), and Nuclear Magnetic Resonance (NMR)to measure chemical structure compared to original PLGA.

INTRODUCTION

Next generation applications require tighter tolerances on the structural, morphological,and chemical composition of thin film surfaces. This is especially the case for the deposition ofhigh quality thin films of organic or thermoplastic or low Tg polymeric materials as opposed topurely inorganic materials where high temperatures and native oxides are used to overcome thehurdles in their fabrication. Depending on the particular application, it may be desirable todeposit films containing single or multilayer structures of different organic or polymericmaterials, homogeneous composite materials, or materials with graded compositions.1,2 In manysituations, it will be necessary to deposit discrete films, achieve conformal coverage, and providehigh quality structures, especially in regard to surface coverage uniformity and thickness control.Thin films of polymeric, inorganic and organic materials also play an important role in batteries,high performance dielectrics, optical data storage, optical communications and displays based onorganic electroluminescent materials.3,4,5,6 Polymer and organic coatings are also essential for thefabrication of chemical and biochemical sensors 7,8, and in biomedical applications ranging frompassivation films for prosthetic or implanted devices to microencapsulation of drugs for targeteddelivery systems.9,10,11

EXPERIMENTAL DETAILS

Matrix assisted pulsed laser evaporation was developed by the Naval Research Laboratory inorder to controllably deposit complex organic thin film coating for use with chemical sensors.12

Complete details of this technique and related experiments have been reported.13

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In MAPLE processing, the “target” consists of a polymer dissolved in a UV absorbingsolvent with high vapor pressure. The purpose of the volatile solvent in the target is to aiddesorption a majority of the laser energy and vaporize when the laser energy is converted tothermal energy by photochemical processes.14,15 Solvents that are sufficiently volatile and do notform a film once evaporated by the laser are ideal. Due to the solvent’s high vapor pressure themolecules of the solvent leave the target with high kinetic energy and collide with the polymer.These collisions transfer the polymer molecules to the substrate via entrainment processes.

All films were deposited at room temperature using a pulsed excimer laser (λ=248 nm)operating at 5 Hz with a 25 ns pulse (FWHM) in an experimental configuration as shown inFigure 1. In this study, 1 wt% PLGA 75/25 (75% LA, 25% GA, Birmingham Polymers), (basicstructure is shown in Figure 1 inset), was dissolved in chloroform (CHCl3) and vortex mixed for20 minutes to dissolve the polymer uniformly. Chloroform was chosen as a solvent in this studydue to a relatively high absorption at 248 nm (43% cm-1) and lower freezing point (-63 °C). Thesolution was poured into a Cu container and flash frozen in liquid nitrogen (LN2). The solidcomposite polymer/CHCl3 target was then inserted onto a LN2 cold stage (temperature ~100°K).After insertion of the target, the system was pumped down to a base pressure of 10-6 Torr, andthen backfilled to 100 mTorr with Ar. Experiments were conducted between 0.1 J/cm2 to 1.0J/cm2, while operating at a repetition rate of 5 Hz.

RESULTS AND DISCUSSION

In order to properly evaluate whether the chemical integrity was changed after ablation,Fourier transform infrared spectroscopy (FTIR) of films and nuclear magnetic resonance (NMR)of dissolved films were performed. Figure 2 shows both native PLGA (a) and MAPLE depositedPLGA FTIR spectra (b). The results from the FTIR spectra show that the deposited filmsresemble the native polymer to a finite degree. Overall, characteristic peaks at 1700 cm-1 andfingerprint regions at 1450 cm-1 appeared similar, however, there was an additonal peak at 760cm-1 not visible in the native PLGA profile that could be identified as C-Cl stretch (Figure 2b.).16

The FTIR results are not conclusive evidence in part due to the film thickness.17

Therefore nuclear magnetic resonance (NMR) was used for further analyze potentialdecomposition. NMR spectra of the native PLGA and high-energy MAPLE samples are shownin Figure 3 (a). Double peaks at 1.6 ppm represent hydrogens in the lactic acid CH3 side groups,

laser pulse

frozen target

volatile solvent ispumped away

cold stage

substrate

laser pulse

H C H

O

OC

PLGA molecule

Figure 0. Schematic illustrations of the basic structure of PLGA (a) and of the matrix-assisted laserprocessing setup for thin film deposition of PLGA onto flat and curved (particulate) substrates (b,c).

(a)

(b)

(c)

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while the multiplets at 4.8 ppm and 5.2 ppm represent the intrachain glycolic acid CH2 groupsand the lactic acid CH units, respectively. The complex nature of the peaks at 4.8 and 5.2 ppmarise from the varying lactic acid and glycolic acid sequences in the polymer backbone.18 TheNMR spectra in Figure 3 (b), (c) show credible evidence that a portion of the polymer wasdegraded to a lower MW species.

8 0 01 2 0 01 6 0 02 0 0 02 4 0 02 8 0 03 2 0 03 6 0 04 0 0 0

P L G A 7 5 / 2 5 N a t i v e

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2 0

4 0

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%T

rans

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sion

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C-Hbend

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OH

(a)

5 0 01 0 0 01 5 0 02 0 0 02 5 0 03 0 0 03 5 0 04 0 0 0

0 . 1 J / c m - 2

0 . 1 5 J / c m - 2

0 . 2 J / c m - 2

0 . 4 J / c m - 2

0 . 5 6 J / c m - 2

0 . 7 6 J / c m - 2

1 . 0 J / c m - 2

W a v e n u m b e r s ( c m - 1 )N

orm

aliz

ed

C-H Bend

C=O

C-HStretch

(b)

?

Figure 2. FTIR spectra for native (a) and MAPLE deposited PLGA (b). The strong correlations ofthe fingerprint regions at 1200 cm-1 and the C-H stretch between the native and deposited filmsgives an indication that the backbone of the deposited PLGA is largely intact following deposition.

0 . 81 . 62 . 43 . 244 . 8

N a t i v e

1 . 0 J / c m - 2

Inte

nsit

y

P P M

(a)

024681 0P P M

Inte

nsit

y

1.0 J/cm2

4,000 pulses100 mTorr Ar

0.76 J/cm2

0.56 J/cm2

0.40 J/cm2

0.20 J/cm2

Deuterated Chloroform CDCl3

Native

(b)

0 . 81 . 62 . 43 . 244 . 8

N a t i v e

0 . 2 J

0 . 4 J

0 . 5 6 J

0 . 7 6 J

1 . 0 J

Inte

nsit

y

P P M

(c)

Figure 3. Nuclear magnetic resonance spectra from native and deposited materials to evaluate thedecomposition effects due to laser-solid interactions. Figure 3(a) shows a comparison of the nativematerial to the MAPLE deposited material at 1.0 J/cm2. Figures 3(b,c) show the comparison of thenative to MAPLE deposited films at fluences ranging from 0.2-1.0 J/cm2.

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With increasing laser fluence the NMR spectra broadens at 1.6, 4.8, and 5.2 ppm,respectively, indicating either a higher signal: noise ratio due to a lower percentage of polymer insolution or an increase in decomposition products. At higher energies, a trend in decompositionof the deposited PLGA to lower molecular weight species, which are chemically identical, maybe observed with differing mobilities, stemming from the breaking of lactic acid and glycolicacid chains.18 These effects are more pronounced in Figure 3(c) where the spectra are combined.

Scanning electron microscopy (SEM) was performed to gain insights into the thickness andmorphological characteristics of the deposited materials. SEM micrographs in figure 4 showdifferences in the surface morphology and film thickness on laser fluence. All of the filmsdeposited, regardless of laser energy, had varied amounts of surface features and 'matrix tracepatterns' on the surface. At higher fluences, the particulate population (25nm - 500nm) becomesmore pronounced and apparent matrix effects are minimized as shown in Figure 4(a-g). Typicalthin film thickness was measured to be on the order of 20-150 nm in Figure 4(h-i).

A comparison with conventional UV-PLD (no solvent) has been performed on solid targets ofPLGA in similar energy regimes from (0.2-1 J/cm2). These results demonstrate similar chemicalstructures to MAPLE deposited PLGA.19 The chemical degradation from the NMR spectra(broadening) overlap with the MAPLE deposited data, while the roughness of the films at lower

1 µm 1 µm 1 µm

1 µm 1 µm 1 µm

1 µm 100 nm 100 nm

(a) 0.10 J/cm2 (c) 0.20 J/cm2

(f) 0.76 J/cm2(e) 0.56 J/cm2(d) 0.40 J/cm2

(h) 0.40 J/cm2(g) 1.0 J/cm2 (i) 1.0 J/cm2

(b) 0.15 J/cm2

Figure 4. Scanning electron microscope images of deposited thin films of PLGA. The SEM micrographsshow trends of particulate formation, showing morphology effects in terms of matrix patterns, particleroughness and droplet formation as a function of laser fluence (a-g). Figure 4 (g, h) illustrate the thicknessregime for the films which ranged from 20-100nm, (images were taken at 50°, 15° tilt, respectively).

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energies is reduced by an order of magnitude. The deposition rate at higher fluence increases byan order of magnitude, suggesting the clear increase over MAPLE without compromising surfacemorphology. Figure 5 shows a comparison to the MAPLE work at both ends of the energyspectrum (0.2-1.0 J/cm2) indicating the morphology and chemical structure of thin films ofPLGA deposited by conventional UV PLD.

CONCLUSIONS AND FUTURE WORK

In conclusion, we have demonstrated successfully the ability to deposit thin films of a fragilebiodegradable polymer using matrix assisted laser processing (MAPLE) with native-likesignatures as obtained from FTIR and NMR characterization. The ability to control thedeposition rate for thin films ranging from 20nm-100nm is an important aspect of the MAPLEprocess. The surface roughness of the deposited films was significantly higher than expectedand further matrix / polymer optimization is required. Significant broadening of the NMRspectra indicate the breakdown of the polymer into lower MW species, which suggests that dueto PLGA’s high absorption at 248nm, MAPLE deposited films will not retain 100% chemicalintegrity.

0 . 81 . 62 . 43 . 244 . 8

N a t i v e

0 . 2 0 J / c m - 2

0 . 3 8 J / c m - 2

1 . 0 J / c m - 2

P P M

Inte

nsit

y

100 nm10 µm 1 µm 10 µm

(a) (b) (c) (d)

(e)

Figure 5. Initial results PLGA films made by conventional UV PLD. Figures (a),(b) representsmooth films deposited at 0.2 J/cm2, a scratch was made due to lack of morphology and thicknessmeasurement. Figures (c),(d) represent films deposited at the highest fluence, 1.0 J/cm2, showingsignificant roughness and increases in deposition rates. The NMR spectra (e) suggest that theamount of degradation at low fluence is similar to that found in the MAPLE deposited materials at248nm.

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ACKNOWLEDGEMENTS

The authors would like to acknowledge Raj Bansal and Dr. Cassandra Fraser for theircontributions to microscopy and characterization.

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