Tricalcium phosphate and tricalcium phosphate/polycaprolactone particulate composite for controlled release of protein

Abstract

β-Tricalcium phosphate (β-TCP) with three different particle size ranges was used to study the effects of particle size and surface area on protein adsorption and release. Polycaprolactone (PCL) coating was applied on the particle systems to investigate its effect on particulate system properties from both structural and application aspects. The maximum loading of 27 mg/g was achieved for 100 nm particles. Bovine serum albumin (BSA) loading amount was controlled by varying the BSA loading solution concentration, as well as the sample powder's surface area. Increasing the surface area of the delivery powder significantly increased loading and release yield. Unlike the samples with low surface area, the lowest particle size samples showed sigmoidal release profile. This indicated that release was governed by different mechanisms for particles with different sizes. While the majority of samples showed no more than 50% release, the 550 nm particles demonstrated 100% release. PCL coating showed no significant ability to attenuate burst release in PBS. However, it led to a steadier release profile as compared to the bare TCP particles. FTIR analysis also proved that the secondary structure of BSA did not change significantly during the adsorption; however, minor denaturation was found during the release. The same results were found when PCL coating was applied on the TCP particles. We envision potential use of TCP and TCP+PCL systems in bone growth factor or orthopedic drug delivery applications in future bone tissue engineering application.

Keywords: Bovine serum albumin release; Denaturation; Particle surface area; Polycaprolactone coating; Tricalcium phosphate.

Figure 1

XRD patterns of powders with different size of: a) 100, b) 550, and c) 1850 nm.

Figure 2

FT-IR spectra of: a) TCP 100 nm, b) TCP+PCL 100 nm, c) TCP 550 nm, d) TCP+PCL 550 nm, e) TCP 1850 nm, f) TCP+PCL 1850 nm, and g) PCL samples.

Figure 3

FT-IR spectra of BSA-loaded samples of: a) TCP 100 nm, b) TCP+PCL 100 nm, c) TCP 550 nm, d) TCP+PCL 550 nm, e) TCP 1850 nm, f) TCP+PCL 1850 nm, and g) BSA.

Figure 4

Surface area values of TCP and TCP+PCL samples(error bars show the standard deviation).

Figure 5

SEM morphologies of bare powders and particulate composites at 20,000X magnification (a) 550nm TCP, (b) 100nm TCP, (c) 1850nm TCP, (d) 550nm PCL+TCP, (e) 100nm PCL+TCP, (f) 1850nm PCL+TCP.

Figure 6

Loaded BSA as a function of initial loading concentration (error bars show the standard deviation).

Figure 7

BSA release profiles from 550nm particles, a) bare and b) PCL coated(error bars show the standard deviation).

Figure 7

BSA release profiles from 550nm particles, a) bare and b) PCL coated(error bars show the standard deviation).

Figure 8

BSA release profiles from 100nm particles, a) bare and b) PCL coated (error bars show the standard deviation).

Figure 8

BSA release profiles from 100nm particles, a) bare and b) PCL coated (error bars show the standard deviation).

Figure 9

BSA release profiles from 1850nm particles, a) bare and b) PCL coated (error bars show the standard deviation).

Figure 9

BSA release profiles from 1850nm particles, a) bare and b) PCL coated (error bars show the standard deviation).

Fig. 10

Schematic presentation of BSA adsorption on a) TCP and b) PCL coated samples.