Mesoporous silica nanoparticles (MSNs), one of the important porous materials, have garnered interest owing to their highly attractive physicochemical features and advantageous morphological attributes. They are of particular importance for use in diverse fields including, but not limited to, adsorption, catalysis, and medicine. Despite their intrinsic stable siliceous frameworks, excellent mechanical strength, and optimal morphological attributes, pristine MSNs suffer from poor drug loading efficiency, as well as compatibility and degradability issues for therapeutic, diagnostic, and tissue engineering purposes. Collectively, the desirable and beneficial properties of MSNs have been harnessed by modifying the surface of the siliceous frameworks through incorporating supramolecular assemblies and various metal species, and through incorporating supramolecular assemblies and various metal species and their conjugates. Substantial advancements of these innovative colloidal inorganic nanocontainers drive researchers in promoting them toward innovative applications like stimuli (light/ultrasound/magnetic)‐responsive delivery‐associated therapies with exceptional performance in vivo. Here, a brief overview of the fabrication of siliceous frameworks, along with discussions on the significant advances in engineering of MSNs, is provided. The scope of the advancement in terms of structural and physicochemical attributes and their effects on biomedical applications with a particular focus on recent studies is emphasized. Finally, interesting perspectives are recapitulated, along with the scope toward clinical translation.

Following a polyelectrolytical complex reaction, the poly-L-ornithine (PLO)-alginate microcapsules were prepared by coating PLO on calcium alginate beads which were produced by a high-voltage electrostatic droplet generator. The biocompatibility of the microcapsules at the molecular level was evaluated through investigating the mRNA expression of pro-inflammatory cytokines; that is, the effect of the PLO coating of alginate beads on the mRNA expression of TNF-α, IL-1β, and IL-6 were measured using the RT-PCR method. The resulting PLO-coated alginate microcapsules have a smooth surface with a mean diameter of 309µm. The molecular biocompatibility studies show that coating microcapsules with PLO has no significant effect on the biocompatibility of alginate microcapsules (p>0.05), and both alginate microcapsules and PLO-coated microcapsules are significantly different from the positive control (p<0.05); however, both are also capable of causing an inflammatory response at a molecular level since both are significantly different from the blank control (p<0.05). Furthermore, with the increase in concentration of microcapsules or co-cultured time, part of the mRNA expression of cytokines is significantly increased. The results also demonstrate that the method used in this study, co-incubating the microcapsules with macrophages and measuring the mRNA expression of cytokines by RT-PCR, may be a useful method for evaluating the biocompatibility of coating materials of microcapsules.

SiO2-hemoglobin-poly(L-lactide) (SiO2-Hb-PLLA) microspheres were prepared in a process of solution-enhanced dispersion by supercritical CO2 (SEDS). SiO2 nanoparticles were loaded with Hb by adsorption firstly and then the Hb-SiO2 nanoparticles were further coated with PLLA by the SEDS process. The resulted microcapsules were characterized by scanning electron microscope (SEM), laser diffraction particle size analyser and Fourier transform infrared spectrometer (FTIR). The drug release profiles were also determined. The Hb-SiO2-PLLA microspheres have a narrow particle size distribution (PDI 0.189) with a mean particle size of 897nm and a drug loading of 7.1%. After coating with PLLA, the drug release from SiO2-Hb-PLLA showed a sustained process mainly in zero-order kinetics; only 3.7% drug was released in the first 24 hours, versus 51.9% for those without coating, which revealed that the coating of PLLA significantly retarded the drug release. The results also indicate that the SEDS process is a typical physical process to produce protein-loaded polymer microspheres without changing the molecular structure of proteins, which is potential in the application of designing proteins drug delivery system.

Following a polyelectrolytical complex reaction, alginate/poly(L-Arginine)-chitosan ternary complex microcapsules were prepared by coating poly(L-Arginine) and chitosan as membrane materials on calcium alginate beads, which were produced by a high-voltage electrostatic droplet generator. The influences on the diameter and uniformity of the calcium alginate beads were studied, and the optimum operating parameters were selected to produce microcapsules. The in vitro drug release behavior and pH stimuli-response of alginate/poly(L-Arginine)-chitosan ternary complex microcapsules were investigated. In comparison with alginate/chitosan microcapsules, alginate/poly(L-Arginine) microcapsules and their corresponding double-membrane microcapsules, alginate/poly(L-Arginine)-chitosan microcapsules released the macromolecular drug in a more sustained and stable way. It was found that they released 85.7% of the bovine erythrocytes hemoglobin (Hb) in 85 hours by approximate first-order kinetics in pH 6.8 PBS. While in a pH 1.0 HCl solution, only 9.6 % of the Hb was released in the first half hour and then the drug release shifted to a flat stage, which indicated that the alginate/poly(L-Arginine)-chitosan microcapsules possessed a pH stimuli-response property. The results suggest that the alginate/poly(L-Arginine)-chitosan ternary complex microcapsules might be a potential colon-targeted drug delivery system for the encapsulation of proteins.

Alginate–chitosan nanocapsules (Alg-CS NCs) were prepared by a two-stage process. The NCs were loaded with two low molecular drugs-tegafur and Mitoxantrone Hydrochloride(DHAD). Results revealed that these two drugs exhibited different drug loading and release characteristics. The drug loading and encapsulation efficiency of tegafur (<1%) were both lower than those of DHAD with the drug loading at about 20%~60% and encapsulation efficiency over 90%. However, tegafur showed a visible burst release phenomenon and the cumulative release rate of tegafur was much higher than that of DHAD.