A Novel Artificial Hemoglobin Carrier Based on Heulandite-Calcium Mesoporous Aluminosilicate Particles.

Tetraethyl-orthosilicate (TEOS)-based nanoparticles are most extensively used as a silica-based hemoglobin carrier system. However, TEOS-based nanoparticles induce adverse effects on the hemoglobin structure. Therefore, a heulandite-calcium-based carrier was investigated as a novel silica-based hemoglobin carrier system. The heulandite-calcium mesoporous aluminosilicate particles (MSPs) were fabricated by a patented tribo-mechanical activation process, according to the manufacturer, and its structure was assessed by X-ray diffraction analysis. Upon hemoglobin encapsulation, alternation in the secondary and tertiary structure was observed. The hemoglobin-particle interactions do not cause heme degradation or decreased activity. Once encapsulated inside the particle pores, the hemoglobin shows increased thermal stability, and higher loading capacity per gram of particles (by a factor of >1.4) when compared to TEOS-based nanoparticles. Futhermore, we introduced a PEGlyted lipid bilayer which significantly decreases the premature hemoglobin release and increases the colloidal stability. The newly developed hemoglobin carrier shows no cytotoxicity to human umbilical vein endothelial cells (HUVEC).

Poly(propylene imine) dendrimer caps on mesoporous silica nanoparticles for redox-responsive release: smaller is better.

To elucidate the importance of the size of capping agents in stimulus-induced release systems from mesoporous silica nanoparticles (MSNs), the effectiveness of poly(propylene imine) dendrimers in controlling the model drug release was studied. MCM-41-type MSNs were synthesized and characterized. Fluorescent compounds (fluorescein disodium salt and carboxyfluorescein) were loaded in the porous structure of the MSNs and entrapped in the silica matrix with the dendrimers of generations I through V by anchoring dendrimers on the MSN surface through disulfide bonds. Stimulus-induced release of the cargo was studied in the presence of dithiothreitol (DTT). Dendrimers of generations I and II were found to be more effective in model drug retention and subsequent release than higher generations. Moreover, MSNs modified with larger amounts of dendrimers lowered the cargo release in the presence of DTT. These findings are of importance for optimizing drug delivery systems based on responsive MSNs as they enable tuning of the amount of the released cargo by choosing the capping agent of appropriate size.

Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica.

With the advancement of drug delivery systems based on mesoporous silica nanoparticles (MSNs), a simple and efficient method regulating the drug release kinetics is needed. We developed redox-responsive release systems with three levels of hindrance around the disulfide bond. A model drug (rhodamine B dye) was loaded into MSNs' mesoporous voids. The pore opening was capped with ß-cyclodextrin in order to prevent leakage of drug. Indeed, in absence of a reducing agent the systems exhibited little leakage, while the addition of dithiothreitol cleaved the disulfide bonds and enabled the release of cargo. The release rate and the amount of released dye were tuned by the level of hindrance around disulfide bonds, with the increased hindrance causing a decrease in the release rate as well as in the amount of released drug. Thus, we demonstrated the ability of the present mesoporous systems to intrinsically control the release rate and the amount of the released cargo by only minor structural variations. Furthermore, an in vivo experiment on zebrafish confirmed that the present model delivery system is nonteratogenic.