Mucoadhesive Mesoporous Silica Particles as Versatile Carriers for Doxorubicin Delivery in Cancer Therapy

Abstract

Due to their structural, morphological, and behavioral characteristics (e.g., large volume and adjustable pore size, wide functionalization possibilities, excellent biocompatibility, stability, and controlled biodegradation, the ability to protect cargoes against premature release and unwanted degradation), mesoporous silica particles (MSPs) are emerging as a promising diagnostic and delivery platform with a key role in the development of next-generation theranostics, nanovaccines, and formulations. In this study, MSPs with customized characteristics in-lab prepared were fully characterized and used as carriers for doxorubicin (DOX). The drug loading capacity and the release profile were evaluated in media with different pH values, mimicking the body conditions. The release data were fitted to Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin kinetic models to evaluate the release constant and the mechanism. The in vitro behavior of functionalized silica particles showed an enhanced cytotoxicity on human breast cancer (MCF-7) cells. Bio- and mucoadhesion on different substrates (synthetic cellulose membrane and porcine tissue mucosa)) and antimicrobial activity were successfully assessed, proving the ability of the OH- or the organically modified MSPs to act as antimicrobial and mucoadhesive platforms for drug delivery systems with synergistic effects.

Keywords: antimicrobial activity; cytotoxicity; doxorubicin carrier; mesoporous silica particles; mucoadhesion test.

Figure 1

FT-IR spectra in absorbance of MS before (M1-M5) (a) and after (D1-D5) (b) DOX encapsulation. Spectra details in the 1800–1400 cm⁻¹ spectral range of MS before (M1-M5) (c) and after (D1-D5) (d) DOX encapsulation, where “M” denoted the MS samples before DOX loading and “D” denoted the MS samples after DOX loading. The 2nd derivative of the IR spectra in the 1800–1400 cm⁻¹ spectral range of MS before (M1-M5) (e) and after (D1-D5) (f) DOX encapsulation. The negative bands in the 2nd derivative spectra correspond to the maxima of absorbance spectra in the same spectral region.

Figure 2

Spectra details in the 3800-3000 cm⁻¹ spectral range of MS before and after DOX encapsulation: M1, M2, D1, D2 (a), M3, M4, D3, D4 (b), and M5, D5 (c), where “M” denoted the MS samples before DOX loading and “D” denoted the MS samples after DOX loading. The 2nd derivative of the IR spectra in the 3800–3000 cm⁻¹ spectral range of MS before and after DOX encapsulation: M1, M2, D1, D2 (d), M3, M4, D3, D4 (e), and M5, D5 (f). The negative bands in the 2nd derivative spectra correspond to the maxima of absorbance spectra in the same spectral region. The marked negative peaks in red revealed the spectra modification after DOX encapsulation.

Figure 3

Spectra details in the 850–600 cm⁻¹ spectral range of MS before and after DOX encapsulation: M1, M2, D1, D2 (a), M3, M4, D3, D4 (b), and M5, D5 (c), where “M” denoted the MS samples before DOX loading and “D” denoted the MS samples after DOX loading. The 2nd derivative of the IR spectra in the 850–600 cm⁻¹ spectral range of MS before and after DOX encapsulation: M1, M2, D1, D2 (d), M3, M4, D3, D4 (e), and M5, D5 (f). The negative bands in the 2nd derivative spectra correspond to the maxima of absorbance spectra in the same spectral region. The marked negative peaks in red revealed the spectra modification after DOX encapsulation.

Figure 4

The CR (%) of DOX during 72 h at pH 1.5, 5, and 7.4 for D1 (a), D2 (b), D3 (c), D4 (d), and D5 (e) fitted with Krosmeyer–Peppas kinetic model. All data are presented as the mean with SD (standard deviation) from at least three independent experiments. Statistical evaluation of the variance differences was conducted using ANOVA at significance levels of p < 0.05.

Figure 5

Cytotoxicity of the DOX-loaded MS samples: (a) D1, (b) D3, and (c) D5 on HeLa, MCF-7, and HGF cell lines. Relative IC₅₀ values were determined by non-linear regression variable slope with four parameters using the Graphpad Prism software. All data are presented as the mean with standard deviation from three independent experiments. Statistical evaluation of differences was conducted using ANOVA at significance levels of p < 0.05.

Figure 6

Mucoadhesion test images registered during the preparation of the tissue mucosa and evaluation of MS by TA.XT Plus texture equipment.

Figure 7

The detachment force (a) and the work of adhesion (b) of the MS samples with a synthetic membrane substrate. All data are shown as the mean with standard deviation from three independent experiments. Statistical evaluation of the variance differences was conducted using ANOVA at significance levels of p < 0.05.

Figure 8

Schematic representation of the preparation protocol of in situ surface organo-modified and/or functionalized silica particles. The purple ball indicates the micelle from which the surfactant forms in water and which further constitutes the template for the formation of mesoporous silica.

Figure 9

The color changes during the loading of DOX: (a) M1 in DOX solution, (b) D1 in DOX solution, (c) D1 in dried state.