Lovastatin release from polycaprolactone coated β-tricalcium phosphate: effects of pH, concentration and drug-polymer interactions

Abstract

The approach of local drug delivery from polymeric coating is currently getting significant attention for both soft and hard tissue engineering applications for sustained and controlled release. The chemistry of the polymer and the drug, and their interactions influence the release kinetics to a great extent. Here, we examine lovastatin release behaviour from polycaprolactone (PCL) coating on β-tricalcium phosphate (β-TCP). Lovastatin was incorporated into biodegradable water insoluble PCL coating. A burst and uncontrolled lovastatin release was observed from bare β-TCP, whereas controlled and sustained release was observed from PCL coating. A higher lovastatin release was observed pH7.4 as compared to pH5.0. Effect of PCL concentration on lovastatin release was opposite at pH7.4 and 5.0. At pH5.0 lovastatin release was decreased with increasing PCL concentration, whereas release was increased with increasing PCL concentration at pH7.4. High Ca(2+) ion concentration due to high solubility of β-TCP and degradation of PCL coating were observed at pH5.0 compared to no detectable Ca(2+) ion release and visible degradation of PCL coating at pH7.4. The hydrophilic-hydrophobic and hydrophobic-hydrophobic interactions between lovastatin and PCL were found to be the key factors controlling the diffusion dominated release kinetics of lovastatin from PCL coating over dissolution and degradation processes. Understanding the lovastatin release chemistry from PCL will be beneficial for designing drug delivery devices from polymeric coating or scaffolds.

Figure 1

(a) Bare TCP, (b) TCP coated by 5% PCL, (c) TCP coated by PCL+LOV, lovastatin was dissolved in 5% PCL solution, (d) AFM height image of TCP coated by 5% PCL. Color scale from dark red to pink is 500 nm.

Figure 2

Percent release of lovastatin with increased PCL and fixed lovastatin concentration in the coating at pH 5.0 (a), and pH 7.4 (b).

Figure 3

Percent and micro gram (inset) release of lovastatin with increased lovastatin and fixed PCL concentration in the coating at pH 5.0 (a), and pH 7.4 (b).

Figure 4

XRD patterns of the TCP samples showing no phase change after LOV release at pH 5.0 and 7.4: (a) as received β-TCP powder, (b) β-TCP sintered at 900 °C for 1 h, (c) after LOV release at pH 5.0, and (d) after LOV release at pH 7.4.

Figure 5

Cumulative Ca²⁺ ion release in the release media from bare and PCL coated scaffolds at pH 5.0 and 7.4 as a function of release time. No detectable Ca²⁺ ion release was observed at pH 7.4 within the ppm (µg/mL) range.

Figure 6

Surface morphology of bare TCP and PCL coated TCP scaffolds after LOV release at pH 5.0: (a) bare TCP (b) TCP coated with a 5 % PCL in acetone (w/v), (c) TCP coated with a 7.5 % PCL in acetone (w/v), and (d) TCP coated with a 10 % PCL in acetone (w/v). All these scaffolds contained 100 µg LOV before release.

Figure 7

Surface morphology of bare TCP and PCL coated TCP scaffolds after LOV release at pH 7.4: (a) bare TCP (b) TCP coated with a 5 % PCL in acetone (w/v), (c) TCP coated with a 7.5 % PCL in acetone (w/v), and (d) TCP coated with a 10 % PCL in acetone (w/v). All these scaffolds contained 100 µg LOV before release.

Figure 8

Inactive lactone and active hydroxyl acid forms of lovastatin.

Figure 9

Schematic representation of the hydrophilic-hydrophobic, and hydrophobic-hydrophobic interactions between lovastatin-PCL in presence of relatively acidic and basic release media.