Mesoporous silica spheres were synthesized by using Stöber theory (MSN-40). Calcination of the mesostructured phase resulted in the starting solid. Organic modification with aminopropyl groups resulted in two MSN-40 materials: named MSN-NH2 and MSN-DQ-40, respectively. These two kinds of samples with different pore sizes (obtained from 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethox-ysilane (NQ-62) and modified NQ-62) showed control of the delivery rate of ibuprofen (IBU) from the siliceous matrix. The obtained sample from modified NQ-62 has an increased loading rate and shows better control of the delivery rate of IBU than the obtained sample from NQ-62. These three solids were characterized using standard solid state procedures. During tests of in vitro drug release, an interesting phenomenon was observed: at high pH (pH 7.45), IBU in all carriers was released slowly; at low pH (pH 4.5), only a part of the IBU was slowly released from this carrier within 25 hours; most IBU was effectively confined in mesoporous material, but the remaining IBU was released rapidly and completely after 25 hours.
Mobil Oil [
This process requires the loading and release of high quantities of drugs due to their special mesoporous structure characteristics [
There are two approaches to making an ibuprofen delivery nanoparticle via Stöber theory [
To 220 ml of deionized water mixed with 80 ml of methanol, there was added ammonia water to a pH of 11.24. Next, 0.58 g of CTAB was added with uniform mixing with a rotating speed of 1200 rpm. The temperature rose to 40°C. Then 5 ml of TEOS was added dropwise. After 1 min, a white precipitate appeared. The reaction proceeded for 3 hours and was then aged for 3 hours. It was filtered to obtain a white solid. The solid was dried at 70°C in air for 24 hours. This was then calcined at 420°C. The material was named MSN-40.
We used polyamine silane coupling agents [
Synthesis rout of MDNQ.
For functionalization, a 2010 report on the multiamine functionalization of mesoporous silica was used [
NQ-62 modified mesoporous silica MSN-40.
The 1.6 g of MDNQ was dissolved in 40 ml aqueous solution, and 400 mg of MSNs was dispersed in solution at 50°C with 1.5 hours’ reaction. This was filtered hot and washed three times with deionized water to remove excess MDNQ. The solid was obtained at 65°C after 24 hours of air drying. The substance was named as MSN-DQ-40.
The 198 mg of IBU was dissolved in 30 ml (6.6 mg/ml). This was treated with 200 mg of MSN-40, MSN-NH2-40, or MSN-DQ-40. The solution was stirred for 36 hours or 72 hours at room temperature with a stirring speed of 500 rpm. The nanoparticles were collected with a 4000 rpm centrifuge for 30 min. The solid was dried at 50°C in air dry oven for 24 hours. To measure IBU loading, 2 ml of the supernatant fluid was diluted to 50 ml and measured at 264 nm on a UV-6100s. This was repeated in triplicate taking the average. The IBU loading quantity was obtained via the following formula [
In our release experiment, each sample is loaded in phosphate buffered saline (PBS) at pH 4.5 and pH 7.45. The nanoparticles (60 mg) were placed in 8000–14000 MWCO dialysis bags with 8 ml PBS. The dialysis solution was 250 ml of PBS at pH 4.5 or pH 7.45 at 37°C. The stirring speed was 500 rpm. Three mL aliquots were taken periodically and measured with absorbance as described above [
Figure
MSN-40 of scanning electron microscope.
Under 50 nm and 20 nm size of the transmission electron microscopy (TEM) picture: MSN-40 (a, d), MSN-NH2-40 (b, e), and MSN-DQ-40 (c, f).
Figure
Parameters of samples: MSN-40, MSN-NH2-40, and MSN-DQ-40.
Sample | Specific surface area |
Pore volume ( |
BJH adsorption pore diameter (nm) |
---|---|---|---|
MSN-40 | 987.79 | 0.75 | 2.42 |
MSN-NH2-40 | 569.58 | 0.033 | 1.91 |
MSN-DQ-40 | 508.75 | 0.096 | 1.91 |
MSN-NH2-40/IBU | 90.41 | 0.006 | 1.76 |
MSN-DQ-40/IBU | 37.014 | 0.016 | 1.74 |
Nitrogen adsorption/desorption isotherms (a) and pore size distributions of samples (b): MSN-40, MSN-NH2-40, MSN-DQ-40, MSN-NH2-40/IBU, and MSN-DQ-40.
The XRD of patterns of MSN-40, MSN-NH2-40 and MSN-DQ-40 are shown in Figure
XRD patterns of samples: MSN-40, MSN-NH2-40, and MSN-DQ-40.
Figures
FTIR spectra of sample: MDNQ (a), NQ-62 (b), MSN-40/MSN-40/IBU (c), and IBU/MSN-NH2-40/IBU/MSN-DQ-40 (d).
Figures
Figure
TG curves of sample: MSN-40/CTAB (black line), MSN-40 (red line), MSN-NH2-40 (blue line), and MSN-DQ-40 (pink line).
Table
IBU-loaded amount of sample: MSN-40, MSN-NH2-40, and MSN-DQ-40.
Sample | Loading (%) 36 h | Loading (%), 72 h |
---|---|---|
MSN-40 | 48.07 | |
MSN-NH2-40 | 10.68 | 46.93 |
MSN-DQ-40 | 49.47 |
Figures
IBU releasing of sample: MSN-40/IBU, MSN-NH2-40/IBU, and MSN-DQ-40/IBU in pH = 7.45 and pH = 4.5 buffer solution.
We demonstrated the feasibility of controlling the delivery rate of drugs occluded in MSN-40 matrixes by functionalizing the pore wall with a silane coupling agent and modified silane coupling agent. For IBU, which contains an acid group, the well-ordered MSN-40 matrixes are functionalized with aminopropyl moieties (namely, MSN-NH2 and MSN-DQ-40) to decrease delivery. They showed pH-responsive control for drug release. At high pH (pH 7.45), IBU drug loaded in MSN-40 matrixes releases slowly within 50 hours; at low pH (pH 4.5), the IBU was slowly released within 25 hours but was released rapidly and completely after 25 hours.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
The authors acknowledge financial support from the high-level innovative talents training project of Guizhou province (QKHPTRC[2016]5658) and the First Graduate Student Scientific Research Fund Projects in Guizhou, China (KYJJ, [2016] 09). They thank LetPub (