Development of a nanoporous and multilayer drug-delivery platform for medical implants

Figures & data

Figure 1 AFM topography images of: (A) PLGA single layer that was spin coated at 53 × g for 30 seconds. (B) PCL single layer that was spin coated at 53 × g for 30 seconds. (C) Dual layer (PLGA [75:25]–PCL) that was spin coated at 53 × g for 30 seconds. (D) Triple layer (PLGA [65:35]–PLGA [75:25]–PCL) that was spin coated at 53 × g for 30 seconds. The scan size is 2.5 μm × 2.5 μm. (E) Corresponding X cross sections of Figure 1B and C that reveal the dimensions of the holes between the spherulites of PCL single layers and the pore sizes of PLGA–PCL dual layers, respectively.

Abbreviations: PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone.

Table 1 AFM data of the surface characteristics of the drug-free polymeric layers

	Rq (nm)	Ry (nm)	Pore depth (nm)	Pore diameter (nm)	Pore density (pores μm^−2)
Single layers
PLGA 75:25	0.2 ± 0.02	2.1 ± 0.3	–	–	–
PCL	5.5 ± 1	55 ± 16	–	–	–
Dual layers	1.1 ± 0.3	14.2 ± 3	2–17	20–170	40–70
Triple layers	0.3 ± 0.06	7 ± 3	1–7	20–150	20–80

Abbreviations: AFM, atomic force microscopy; PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone; R_y, peak-to-valley distance; R_q, root mean square roughness.

Table 2 AFM data of triple layers (PLGA [65:35]–PLGA [75:25]–PCL) fabricated under variable experimental conditions

Polymer concentration (mg mL^−1)	Spinning speed (rpm)	Pore depth (nm)	Pore diameter (nm)	Pore density (pores per μm^2)	Rq (nm)
10	24 × g	1–7	20–120	25	0.4
10	53 × g	1–6	20–150	20	0.5
5	24 × g	3–8	20–310	43	1.8

Abbreviations: AFM, atomic force microscopy; PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone; R_q, root mean square roughness.

Figure 2 AFM topography images of the triple layer (PLGA [65:35]–PLGA [75:25]–PCL) fabricated under variable experimental conditions. (A) Polymer concentration of 10 mg mL⁻¹, spin coated at 24 × g for 30 seconds; (B) polymer concentration of 10 mg mL⁻¹, spin coated at 53 × g for 30 seconds; and (C) polymer concentration of 5 mg mL⁻¹, spin coated at 24 × g for 30 seconds.

Note: The scan size is 10 μm × 10 μm.

Abbreviations: PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone.

Figure 3 The experimental pseudodielectric functions (symbols) and the corresponding simulated ones (solid lines) determined by the use of best-fit results or the single-layer polymeric films: (A) PLGA 75:25–c-Si, (B) PCL–c-Si, (C) the dual-layer PLGA (PLGA [75:25]–PCL-c-Si), and (D) the triple-layer (PLGA [65:35]–PLGA [75:25]–PCL-c-Si).

Note: The insets in the figures show the geometrical model, which was applied in each case, and the respective thicknesses of the polymeric films derived by the fitting analysis.

Abbreviations: PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone; Si, silicon.

Figure 4 The real part of the bulk complex refractive index n calculated using best-fit parameters of the SE data analysis for the single-layer polymeric films PLGA 75:25 and PCL, the PLGA 75:25 and PCL from the dual-layer film, and the PLGA 65:35 and PCL from the triple-layer film.

Abbreviations: SE, spectroscopic ellipsometry; PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone.

Table 3 AFM data of platelet adhesion onto drug-free and drug-loaded triple layer (PLGA [65:35]–PLGA [75:25]–PCL)

	Before platelet adhesion	After 1 hour platelet adhesion	After 2 hours platelet adhesion
Rq (nm)
Drug-free	0.3	52.7	58.2
Drug-loaded	1.4	33.7	29.7
Ry (nm)
Drug-free	9.5	411.3	565.5
Drug-loaded	12.5	246.3	245.4

Abbreviations: AFM, atomic force microscopy; PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone; R_y, peak-to-valley distance; R_q, root mean square roughness.

Figure 5 AFM topography images of the triple layer (PLGA [65:35]–PLGA [75:25]–PCL) loaded with dipyridamole: (A) as fabricated by spin coating at 53 × g for 30 seconds and (B) after its degradation in PBS solution for 15 minutes.

Note: The scan size is 2.5 μm × 2.5 μm.

Abbreviations: AFM, atomic force microscopy; PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone; PBS, phosphate buffered saline

Figure 6 AFM topography images of platelets onto (A and B) drug-free and (C and D) dipyridamole-loaded triple layers (PLGA [65:35]–PLGA [75:25]–PCL). Both samples were spin coated at 53 × g for 30 seconds. (A) drug-free sample after 1 hour of platelet adhesion; (B) drug-free sample after 2 hours of platelet adhesion; (C) drug-loaded sample after 1 hour of platelet adhesion; and (D) drug-loaded sample after 2 hours of platelet adhesion with a typical cross section (inset).

Note: The scan size is 20 μm × 20 μm.

Abbreviations: AFM, atomic force microscopy; PLGA, poly (DL-lactide-co-glycolide); PCL, polycaprolactone.

Figure 7 The dipyridamole cumulative release profiles from the three layer samples.

Note: The inset graph depicts the burst effect that occurs during the first 5 hours.