Integration of Mesoporous Bioactive Glass Nanoparticles and Curcumin into PHBV Microspheres as Biocompatible Composite for Drug Delivery Applications

Abstract

Bioactive glasses (BGs) are being increasingly considered for biomedical applications. One convenient approach to utilize BGs in tissue engineering and drug delivery involves their combination with organic biomaterials in order to form composites with enhanced biocompatibility and biodegradability. In this work, mesoporous bioactive glass nanoparticles (MBGN) have been merged with polyhydroxyalkanoate microspheres with the purpose to develop drug carriers. The composite carriers (microspheres) were loaded with curcumin as a model drug. The toxicity and delivery rate of composite microspheres were tested in vitro, reaching a curcumin loading efficiency of over 90% and an improving of biocompatibility of different concentrations of MBGN due to its administrations through the composite. The composite microspheres were tested in terms of controlled release, biocompatibility and bioactivity. Our results demonstrate that the composite microspheres can be potentially used in biomedicine due to their dual effects: bioactivity (due to the presence of MBGN) and curcumin release capability.

Keywords: PHBV; bioactive glass nanoparticles; composite microspheres; drug delivery systems.

Figure 1

Average particle size distribution of (a) MBGN and (b) composite microspheres (CM) measured by laser diffraction.

Figure 2

SEM micrographs of (a) blank PHBV microspheres; (b) PHBV/MBGN composite microspheres at 90:10 ratio, and PHBV/MBGN composite microsphere at higher ratios; (c) 60:40; and (d) 50:50.

Figure 2

SEM micrographs of (a) blank PHBV microspheres; (b) PHBV/MBGN composite microspheres at 90:10 ratio, and PHBV/MBGN composite microsphere at higher ratios; (c) 60:40; and (d) 50:50.

Figure 3

FTIR spectrum of a composite microsphere (70:30 PHBV/MBGN ratio). The detected peaks are discussed in the text.

Figure 4

XRD pattern of a composite microsphere (70:30 PHBV/MBGN ratio). The identified peaks are discussed in the text.

Figure 5

Curcumin entrapment efficiency (CEE) in microspheres at different PHBV/MBGN ratios (error bars show the Standard Deviation).

Figure 6

Cumulative release kinetic of curcumin from composite microspheres in PBS at a 90:10 (PHBV/MBGN) ratio in PBS.

Figure 7

Cell viability of MG-63 cells treated with control (cells without any treatment), pure PHBV microspheres and composite microspheres at different MBGN ratios (ten-fold dilutions of 1 mg/mL), after 24 h of incubation. (* corresponds to p-value ≤ 0.05).

Figure 8

Fluorescence micrographs of MG-63 cells treated with (a) composite microspheres at 50:50 (PHBV/MBGN) ratio and a (b) similar amount of free MBGN after 24 h (bar size is 10 µm).

Figure 9

Cell viability of MG-63 cells treated with control (cells without any treatment), pure PHBV microspheres, and microspheres at different MBGN ratios (ten-fold dilutions of 1 mg/mL), after seven days of incubation. (* corresponds to p-value ≤ 0.05).

Figure 10

Fluorescence microscopy micrographs of MG-63 cells treated with (a) composite microspheres at 50:50 (PHBV/MBGN) ratio and (b) same proportion of free MBGN, after seven days of incubation (bar size is 20 mm).

Figure 11

(a) XRD patterns of composite microspheres PHBV/MBGN (90:10) after zero and seven days of immersion in SBF, and (b) SEM micrograph of composite microspheres (same ratio) after seven days of immersion in SBF.