A Comprehensive Study of Drug Loading in Hollow Mesoporous Silica Nanoparticles: Impacting Factors and Loading Efficiency

Abstract

Although hollow mesoporous silica nanoparticles (HMSNs) have been intensively studied as nanocarriers, selecting the right HMSNs for specific drugs still remains challenging due to the enormous diversity in so far reported HMSNs and drugs. To this end, we herein made a comprehensive study on drug loading in HMSNs from the viewpoint of impacting factors and loading efficiency. Specifically, two types of HMSNs with negative and positive zeta potential were delicately constructed, and three categories of drugs were selected as delivery targets: highly hydrophobic and lipophobic (oily), hydrophobic, and hydrophilic. The results indicated that (i) oily drugs could be efficiently loaded into both of the two HMSNs, (ii) HMSNs were not good carriers for hydrophobic drugs, especially for planar drugs, (iii) HMSNs had high loading efficiency towards oppositely charged hydrophilic drugs, i.e., negatively charged HMSNs for cationic molecules and vice versa, (iv) entrapped drugs would alter zeta potential of drug-loaded HMSNs. This work may provide general guidelines about designing high-payload HMSNs by reference to the physicochemical property of drugs.

Keywords: cavity diameter; hollow mesoporous silica nanoparticle; loading efficiency; pore size; zeta potential.

Figure 1

(a) Schematic diagram of the synthesis of n-HMSNs and p-HMSNs. TEM images of (b) SiO₂-1 NPs, (c) n-HMSNs, (d) SiO₂-2 NPs, (e) p-HMSNs and their respective particle size distributions (inset). (f) Hydrodynamic size and (g) zeta potential of these NPs.

Figure 2

FTIR spectra of n-HMSNs (black line) and p-HMSNs (red line). Black arrows indicated the respective vibrations of the bond.

Figure 3

(a) N₂ adsorption-desorption isotherms and (b) corresponding BJH pore size distributions of n-HMSNs (triangle) and p-HMSNs (circle). The data in (b) were calculated from branches of the desorption isotherm in (a).

Figure 4

TEM images of (a) n-HMSNs and (b) p-HMSNs loaded with PFH. (c) The oxygen release profile of O₂-saturated water, n-HMSNs, p-HMSNs, PFH@n-HMSNs, and PFH@p-HMSNs under heat directly and the upper right inset is the picture of p-HMSNs before (left) and after (right) PFH loading in aqueous suspension under room light.

Figure 5

(a) UV-vis absorption spectra of ZnPc, C6, and PpIX in DMSO (dash line) and p-HMSNs (solid line), respectively. The absorption bands of ZnPc were enlarged and denoted by the arrow. The insets to the right edge are pictures of respective drug-loaded p-HMSNs in aqueous suspension (under room light). (b) UV-Vis absorption spectra of ZnPc, C6, and PpIX in stock solution (dash line) and washing solution treated with n-HMSNs (solid line) and p-HMSNs (dash-dot line), respectively.

Figure 6

Zeta potential of drug-loaded n-HMSNs (left) and p-HMSNs (right). The loaded drugs denoted with different colors were ZnPc, C6, PpIX, NAPP, ICG, and RhB in sequence (from left to right).

Figure 7

(a) UV-Vis absorption spectra of RhB, ICG, and NAPP in water (dash line) and in p-HMSNs (solid line), respectively. The insets to the right edge were pictures of corresponding drug-loaded p-HMSNs in aqueous solutions (under room light). (b) UV-Vis absorption spectra of RhB, ICG, and NAPP in stock solution (dash line) and washing solution treated with n-HMSNs (solid line) or p-HMSNs (dash-dot line), respectively.

Figure 8

Overlay of the bright field with differential interference contrast (DIC) and confocal fluorescence images of Hela cells loaded with respective drug-loaded n-HMSNs (upper) and p-HMSNs (lower). The fluorescence was collected at 665–705 nm, 500–550 nm, 581–654 nm, 581–654 nm, 765–900 nm, and 581–654 nm, respectively, under the excitation of 638 nm, 405 nm, 405 nm, 405 nm, 638 nm, and 561 nm light. From left to right is ZnPc, C6, PpIX, NAPP, ICG, RhB in sequence (scale bar: 50 μm).