A study of carboxylic-modified mesoporous silica in controlled delivery for drug famotidine

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Abstract

A series of pure silica MSU and carboxylic-modified MSU materials were prepared. The formation of mesoporous silica materials with terminal carboxylic groups on pore surface was performed by the acid-catalyzed hydrolysis of cyano to carboxylic. Then their potential applications in controlled drug delivery carriers were investigated. Drug famotidine was selected as a model molecule out of the consideration of the terminal amino groups in its molecule. The adsorption experiments show significant adsorption of famotidine on the carboxylic-modified MSU materials. And, the functionalization level of carboxylic groups has been found to be the key factor affecting the adsorption capacities of the modified MSU materials for famotidine. Subsequently, three kinds of release fluids, including simulated gastric medium, simulated intestinal medium, and simulated body fluid, were used to test the famotidine release rate from the carboxylic-modified MSU material. Obvious delayed effect has been observed for the famotidine release from the carboxylic-modified mesoporous silica material under the in vitro assays.

Graphical abstract

Carboxylic-modified mesoporous silica MSU material was used as drug carrier, and the in vitro assays reveal the release of famotidine from the carboxylic-modified mesoporous silica material can be controlled to a high degree.

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Introduction

Porous silica materials employed as convenient drug reservoirs in controlled drug delivery have received much attention these years. Zeolites, typical microporous materials, have been investigated for use as carriers for a variety of drugs [1], [2], [3]. However, for the guest molecules of pharmaceutical interest, which are usually larger than 2 nm, zeolites are not appropriate to be used as carriers due to the relatively small pore size. Interestingly, the Mobil Oil Corporation discovered the M41s group of mesoporous materials in 1992 [4]. And then various kinds of mesoporous materials (such as SBA-15, MSU) have been successfully synthesized over the last few years [5], [6]. Generally, mesoporous silica materials have very high specific surface areas and large pore volumes. These useful properties allow them to accept high amount of drug molecules. Moreover, mesoporous silica materials have tunable pore sizes ranging from 2 to several ten nanometers, and the pore sizes can be well adjusted by choosing appropriate surfactant template and reaction conditions, enlarging the applications of porous silica in hosting large guest molecules [7], [8], [9], [10], [11].

In 2001, Vallet-Regí and co-workers primarily reported the application of silica MCM-41 for controlled release of ibuprofen under the in vitro assays [12]. Afterwards, several research groups investigated the drug adsorption and release properties of mesoporous silica materials [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. An ideal mesoporous carrier with high specific surface area, large pore volume, and appropriate pore size (larger than the kinetic diameter of drug) was beneficial to increasing its adsorption capacity for drug [14], [16]. Ibuprofen, which contains a terminal carboxylic group, has been much documented [12], [13], [14], [15], [16], [17], [18], [19]. Ibuprofen can be impregnated into mesoporous silica materials by reacting with the active groups on the mesoporous framework, for instance, by the hydrogen bond interaction with surface silanol groups [12], [16], by the coulombic interaction with functional aminopropyl groups [13], and even through the ester function with the epoxide ring opening of glycidoxypropyl [15]. As yet, to the best of our knowledge, how to apply mesoporous silica carrier system to impregnate a new kind of model drug molecule for controlled delivery is of keen interest.

Herein, famotidine was selected as a model drug molecule. Different from ibuprofen molecule containing a terminal carboxylic group, famotidine molecule contains terminal amino groups. In addition, famotidine has two well-known crystal structural dimensions of 1.7862 nm×0.5329 nm×1.8307 nm (molecular volume of 1.4431 nm3) and 1.1978 nm×0.7196 nm×1.6812 nm (molecular volume of 1.4281 nm3) [23], making it very appropriate to be impregnated into the pore channels of mesoporous materials. In our previous work [24], a preliminary result was reported about the effective adsorption of the carboxylic-modified mesoporous silica SBA-15 materials for drug famotidine. It has been found that the adsorption for famotidine depends strongly on the functionalization levels of carboxylic incorporated on the pore surface the modified mesoporous SBA-15 materials. Also, the impregnated amount of famotidine was affected by the adsorption experimental conditions, including pH value, solvent nature and initial famotidine concentration in the impregnation mixture. The purpose of this work was to obtain further controlled famotidine release from the carboxylic-modified mesoporous silica materials. MSU-type mesoporous silica materials modified by carboxylic groups were investigated as drug carriers. The characterization of the mesoporous silica materials and their adsorption and release properties for famotidine were described in detail.

Section snippets

Materials

The starting materials employed in this study were tetraethoxysilane (TEOS, 99%, TSR), surfactant C11–15H22–30(CH2CH2O)9H (AEO9, HenKel), 2-cyanopropyltriethoxysilane (CPTES, 95%, Aldrich), sulfuric acid (H2SO4, 98%, SCR), methanol (CH3OH, Anhydrous, SCR), ethanol (C2H5OH, Anhydrous, SCR), sodium fluoride (NaF, 99%, SCR) and famotidine (C8H15N7O2S3, 99.9%, QDPF). All chemicals were used as received. The structural formula of famotidine is shown in Scheme 1.

Synthesis

The preparation of mesoporous silica

General features of the synthesized materials

The modified mesoporous materials possess XRD patterns with appearances typical of those of an MSU-type wormlike mesostructure, featuring a single peak at low 2θ angles usually between 1° and 3° [25], [26]. The d100 spacings decrease from 7.36 to 6.17 nm with enhancing the molar ratio of CPTES/(CPTES+TEOS) in the initial synthesis mixture (see Table 1). Evidence for disordered, wormlike mesostructure in the modified samples is provided by typical transmission electron micrograph image (see Fig.

Conclusions

It has been shown that the adsorption capacities of the carboxylic-modified mesoporous silica MSU materials for famotidine are mainly depended on the functionalization levels of carboxylic groups. In vitro release of famotidine in carboxylic-modified MSU material shows obvious delayed effect when compared with famotidine dissolution under the same conditions. The famotidine release kinetics can be controlled by the carrier effect of the carboxylic-modified MSU mesostructure and by the choice of

Acknowledgment

This work was supported by the Chinese National Key Basic Research Special Foundation (Grant no. 2000048001).

References (35)

  • A. Rivera et al.

    Stud. Surf. Sci. Catal.

    (2001)
  • H.H.P. Yiu et al.

    Microporous Mesoporous Mater.

    (2001)
  • P. Horcajada et al.

    Microporous Mesoporous Mater.

    (2004)
  • Y. Zhu et al.

    Microporous Mesoporous Mater.

    (2005)
  • A.L. Doadrio et al.

    J. Control. Release

    (2004)
  • M. Vallet-Regí et al.

    Solid State Ion.

    (2004)
  • M. Vallet-Regí et al.

    Solid State Sci.

    (2005)
  • G.G. Ferenczy et al.

    J. Mol. Struct. (Theochem)

    (2000)
  • Q. Tang et al.

    Stud. Surf. Sci. Catal.

    (2005)
  • Y.J. Gong et al.

    Microporous Mesoporous Mater.

    (2001)
  • T. Higuchi

    J. Pharm. Sci.

    (1963)
  • A. Dyer et al.

    J. Helminthol.

    (2000)
  • K.A. Fisher et al.

    Chem. Eur. J.

    (2003)
  • J.S. Beck et al.

    J. Am. Chem. Soc.

    (1992)
  • D. Zhao et al.

    Science

    (1998)
  • S.S. Kim et al.

    Science

    (1998)
  • Y.-J. Han et al.

    J. Am. Chem. Soc.

    (1999)
  • Cited by (0)

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