Dear Sushikumar,

Yes. See the following:

Iran J Pharm Res. 2015 Winter; 14(1): 27–34.

PMCID: PMC4277616

Preparation and Characterization of Rifampin Loaded Mesoporous Silica Nanoparticles as a Potential System for Pulmonary Drug Delivery

Meysam Mohseni,a Kambiz Gilani,b and Seyed Alireza Mortazavia,c,*

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Abstract

The goal of this research is to determine the feasibility of loading rifampin into mesoporous silica nanoparticles. Rifampin was selected as a model lipophilic molecule since it is a well-documented and much used anti tuberculosis drug. The mesoporous silica nanoparticles were prepared by using tetraethyl ortho silicate and cetyltrimethyl ammonium bromide (as surfactant). The prepared nanoparticles were characterized in terms of their particle size measurement and porosimetry. The results showed that the particle size is 218 ± 46 nm (mean ± SD) and surface area is 816 m2g-1. In order to load rifampin within the mesopores, adsorption experiments using three different solvents (methanol, water and dimethyl sulfoxide) were carried out. The loading procedure resulted in a significant improvement in the amount of rifampin loaded into mesoporous silica nanoparticles and methanol was found to be a suitable solvent, providing a drug entrapment efficiency of 52 %. Rifampin loaded nanoparticles underwent different in-vitro tests including, SEM and drug release. The in-vitro drug release was investigated using buffer phosphate (pH=7.4). Regarding the drug release study, a biphasic pattern of release was observed. The drug-loaded mesoporous silica nanoparticles were capable of releasing 95% of their drug content after 24 h, following a faster release in the first four hours. The prepared rifampin loaded nanoparticles seem to have potential for use as a pulmonary drug delivery.

For more details, see attached paper.

Hoping this will be helpful,

Rafik

Thank you for your answer and explanation. As written in the ref. provided water silica interactions reduce the entrapment efficiency ? Can you explain how? OR Why? It has something to do with the water double layer formation on silicas?

In my experience is it is very rare to find a work in which water or buffer is used for loading may because water OR buffers (which are made in water of course) are not suitable solvents for loading.

Dear Sushikumar,

Please note that the water was used in the preparation, then the particles were centrifuged and extracted with ethanol. Therefore, the final product does not have any water.

Synthesis of MSN

The mesoporous silica nanoparticles were prepared using a general method where TEOS was added into an aqueous solution containing CTAB, ethanol, and additives such as inorganic salts, DEA or TEA. The method used in this study was as follows: 6.4 mL of water (0.36 mol), 0.9 g of ethanol (0.015 mol), 0.28 g of CTAB (0.786 mmol) and 0.02 g of DEA (0.19 mmol) were mixed and stirred in a water bath at 40 ˚C for 30 min. Then 0.73 mL of TEOS (3.25 mmol) was added into the mixture dropwise within 2 min under stirring. The solution turned white gradually. A further 2 h stirring was necessary. After that, the solution was cooled to room temperature. The white powder was centrifuged and washed with distilled water and ethanol. The surfactant (CTAB) was extracted by refluxing the obtained mesoporous materials (1 g) at 80 °C with 60 mL ethanol and addition of a small amount of concentrated HCl. The final product was obtained by centrifugation and washed with ethanol for several times (27).

Rafik

Thanks again. But I think you didn't get my point actually I was referring to drug loading only and not to the synthesis conditions. The reason for obtaining low drug loading in water is exactly what? As you mentioned in the paper low drug entrapment efficiency in water.

Hi Sushil, I think that low loading in water can be due to the fact that surface silanols of silica materials are usually in interaction with water so this can compete with the successful interaction with the drug. When I was working with fluorescent dyes adsorbed in MCM41 I used to outgass the MCM41 before the contact with dye solution, and I saw an increase in loading (in that case I was not working in water or buffer, but in organic solvents). In any case, I do not think that we can draw a general conclusion because the loading conditions should be modulated on the basis of both the structure and solubility od the drug and the surface properties of the mesoporous silica (functional groups, etc)

Ivana

Hi Sushil, I think that low loading in water can be due to the fact that surface silanols of silica materials are usually in interaction with water so this can compete with the successful interaction with the drug. When I was working with fluorescent dyes adsorbed in MCM41 I used to outgass the MCM41 before the contact with dye solution, and I saw an increase in loading (in that case I was not working in water or buffer, but in organic solvents). In any case, I do not think that we can draw a general conclusion because the loading conditions should be modulated on the basis of both the structure and solubility od the drug and the surface properties of the mesoporous silica (functional groups, etc)

Ivana

Hi Ivana,

Thank you for your answer.

I agree that water silica (silanols) interactions may lead to low loading as it can reduce the interactions of drug molecules with the silica surface inside the pores.

But it is very rare that water is used for loading of any type of molecules (drug, dyes etc). In fact the reference provided by dr. Karaman above is the only one of this case where water is used for loading.

Anyway thanks to all. Do not hesitate to update me on this if you get any more information or references.

More simpler case for drug loading is to use solvents easy to evaporate. For drug loading you wish that drug redissolves in biological fluid. For using water you would need to find a condition to precipitate onto the surface, which is different from condition in biological fluid with suitable solubility. However, even when you find a suitable condition precipitation likely will cover surface unevenly. 

 Rafik Karaman ·

sir y u used DEA 

Drug loading can be done in water, provided that the drug is fairly soluble and it has stronger interactions with the silanol surface groups than water. Common strategies to increase the drug loading fraction are to use concentrated drug solutions (near the drug solubility limit) or to evaporate the solution (although the drug might crystallize on the particle exterior surface).

A particular case in which water can be better than organic solvents is when the drug can form a highly water soluble salt, preferably a positively charged one ( silanols are negatively charged at pH greater than 2). You can see an example in one of my papers, in which using water/HCl resulted in better drug loading than organic solvents (acetonitrile, ethanol) here: DOI: 10.1039/c4ra11224e .

The main problem with common buffers is that the salts will also be adsorbed onto the silica surface, and the electrostatic interactions between salt cations and silanols will in general be higher than silanols-drug.