Electrosprayed Stearic-Acid-Coated Ethylcellulose Microparticles for an Improved Sustained Release of Anticancer Drug

Abstract

Sustained release is highly desired for "efficacious, safe and convenient" drug delivery, particularly for those anticancer drug molecules with toxicity. In this study, a modified coaxial electrospraying process was developed to coat a hydrophobic lipid, i.e., stearic acid (SA), on composites composed of the anticancer drug tamoxifen citrate (TC) and insoluble polymeric matrix ethylcellulose (EC). Compared with the electrosprayed TC-EC composite microparticles M1, the electrosprayed SA-coated hybrid microparticles M2 were able to provide an improved TC sustained-release profile. The 30% and 90% loaded drug sustained-release time periods were extended to 3.21 h and 19.43 h for M2, respectively, which were significantly longer than those provided by M1 (0.88 h and 9.98 h, respectively). The morphology, inner structure, physical state, and compatibility of the components of the particles M1 and M2 were disclosed through SEM, TEM, XRD, and FTIR. Based on the analyses, the drug sustained-release mechanism of multiple factors co-acting for microparticles M2 is suggested, which include the reasonable selections and organizations of lipid and polymeric excipient, the blank SA shell drug loading, the regularly round shape, and also the high density. The reported protocols pioneered a brand-new manner for developing sustained drug delivery hybrids through a combination of insoluble cellulose gels and lipid using modified coaxial electrospraying.

Keywords: anticancer; anticancer drug; coaxial electrospraying; ethylcellulose; insoluble gels; microparticle; stearic acid; sustained release.

Figure 1

A diagram showing the modified coaxial electrospraying system, its main components, and key information about the working process.

Figure 2

The coaxial electrospraying apparatus and observations of the working processes: (a) a digital picture of the electrospraying apparatus, with the upper left inset showing the concentric spraying head; (b) a digital picture showing the connection of the working fluids and the transferring of electrostatic energy; (c,d) a single-fluid electrospraying process experienced by the core solidable TC-EC solution under different magnifications for preparing the microparticles M1; (e,f) the digital photos of modified coaxial electrospraying processes for observing the whole process and the compound Taylor cone for producing the microparticles M2, respectively.

Figure 3

The morphologies and diameters of the electrosprayed microparticles: (a,b) SEM images of microparticles M1 at different magnifications; (c) the diameters of microparticles M1 and their size distributions; (d,e) SEM images of microparticles M2 at different magnifications; (f) the diameters of microparticles M2 and their size distributions.

Figure 4

Inner structures of the electrosprayed microparticles: (a) TEM images of microparticles M1; and (b) TEM images of the microparticles M2.

Figure 5

The microformation mechanisms: (a) the single-fluid electrospraying for producing microparticles M1; (b) the modified coaxial electrospraying for preparing microparticles M2; and (c) the different materials processing capabilities of traditional coaxial electrospraying and modified coaxial electrospraying processes; the case (II) represents the SA-coated core–shell microparticles M2 in this work.

Figure 6

The ATR-FTIR spectra of the raw materials (TC, EC, and SA) and their electrosprayed microparticles (M1 and M2); the molecular formulas of EC, SA, and TC.

Figure 7

XRD patterns of the raw materials (TC, EC, and SA) and their electrosprayed microparticles (M1 and M2); the potential hydrogen bonds among the three components in the core–shell microparticles M2.

Figure 8

The drug sustained-release functional performances and the related drug controlled-release mechanisms: (a) The full time period drug sustained-release profiles of microparticles M1 and M2; (b) The first 4 h drug release profiles of the particles M1 and M2; (c) The regressed drug release time periods for releasing a certain percentage (30%, 50%, and 90%) of TC from the microparticles M1 and M2; (d) The regressed drug release mechanism for microparticles M1; (e,f) The regressed drug release mechanisms for microparticles M2 for the whole time period and from the 4th hour to the final time point, respectively.

Figure 9

A sketch showing those factors that have co-acted to promote an improved sustained release of TC from the electrosprayed microparticles M2, in which a core insoluble gel composite is coated by a lipid shell layer.