9568
Langmuir 2005, 21, 9568-9575
Functionalized SBA-15 Materials as Carriers for Controlled Drug Delivery: Influence of Surface Properties on Matrix-Drug Interactions S.-W. Song, K. Hidajat, and S. Kawi* Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 119260 Received April 30, 2005. In Final Form: July 19, 2005 Mesoporous SBA-15 materials were functionalized with amine groups through postsynthesis and onepot synthesis, and the resulting functionalized materials were investigated as matrixes for controlled drug delivery. The materials were characterized by FTIR, N2 adsorption/desorption analysis, ζ potential measurement, XRD, XPS, and TEM. Ibuprofen (IBU) and bovine serum albumin (BSA) were selected as model drugs and loaded onto the unmodified and functionalized SBA-15. It was revealed that the adsorption capacities and release behaviors of these model drugs were highly dependent on the different surface properties of SBA-15 materials. The release rate of IBU from SBA-15 functionalized by postsynthesis is found to be effectively controlled as compared to that from pure SBA-15 and SBA-15 functionalized by one-pot synthesis due to the ionic interaction between carboxyl groups in IBU and amine groups on the surface of SBA-15. However, SBA-15 functionalized by one-pot synthesis is found to be more favorable for the adsorption and release of BSA due to the balance of electrostatic interaction and hydrophilic interaction between BSA and the functionalized SBA-15 matrix.
Introduction Over the past three decades, there has been rapid growth in the area of drug delivery which is due to the underlying principle that drug delivery technology can bring both commercial and therapeutic values to health care products. Among the various materials employed in controlled drug delivery systems, polymeric materials provide the most important avenues for research and commercial applications. However, recently, there has been growing interest in the use of mesoporous materials as controlled drug delivery matrixes because they have several attractive features, such as stable uniform mesoporous structures, high surface areas, tunable pore sizes with narrow distributions, and well-defined surface properties,1-8 thus allowing them to adsorb certain kinds of drugs and release these drugs in a more reproducible and predicable manner. It has been shown that both small and large molecular drugs can be entrapped within the mesopores by an impregnation process and liberated via a diffusioncontrolled mechanism. The discovery of triblock copolymer templated SBA-15 with large, controlled pore size and highly ordered hexagonal topology has opened the way to do intriguing experiments inside the resulting channel structures.9 By anchoring a variety of functional groups on the internal * To whom correspondence should be addressed. Phone: +6568746312. Fax: +65-67791936. E-mail:
[email protected]. (1) Vallet-Regi, M.; Ra´mila, A.; del Real, R. P.; Pe´rez-Pariente, J. Chem. Mater. 2001, 13, 308-311. (2) Mun˜oz, B.; Ra´mila, A.; Pe´rez-Pariente, J.; Dı´za, I.; Vallet-Regi, M. Chem. Mater. 2003, 15, 500-503. (3) Tourne´-Pe´teilh, C.; Lerner, D. A.; Charnay, C.; Nicole, L.; Be´gu, S.; Devoisselle, J. M. ChemPhysChem. 2003, 3, 281-286. (4) Mal, N. K.; Fujiwara, M.; Tanaka, Y. Nature 2003, 421, 350-353. (5) Lai, C. Y.; Trewyn, B. G.; Jeftinija, D. M.; Jeftinija, K.; Xu, S.; Jeftinija, S.; Lin, V. S. Y. J. Am. Chem. Soc. 2003, 125, 4451-4459. (6) Doadrio, A. L.; Sousa, E. M. B.; Doadrio, J. C.; Pe´rez-Pariente, J.; Izquierdo-Barba, I.; Vallet-Regi, M. J. Controlled Release 2004, 97, 125-132. (7) Cavallaro, G.; Pierro, P.; Palumbo, F. S.; Testa, F., Pasqua, L.; Aiello, R. Drug Delivery 2004, 11, 41-46. (8) Xue, J. M.; Shi, M. J. Controlled Release 2004, 98, 209-217.
surfaces, the sorption capacity and behavior of SBA-15 could be substantially altered. These properties have led SBA-15 to some intriguing applications, such as selective adsorption of heavy or noble metal,10,11 enzyme immobilization for biocatalysis,12-14 and immobilization of large chelating groups.15 In light of its potential application in the area of drug delivery, there have been attempts recently to apply pure SBA-15 as a drug host.6,8 However, for pure SBA-15, there exist only silanol groups on the channel walls, and these silanol groups simply form weak intermolecular hydrogen bonds with drugs; hence, they are not strong enough to hold drugs and allow them to be released in a sustained manner. The need to synthesize suitable carriers to have specific host-guest interactions with drugs led us to introduce functional groups on the surface of SBA-15. It has been reported that the organic functionalization of SBA-15 can be achieved via two different routes, i.e., one-pot synthesis (or co-condensation)16,17 and postsynthesis (or silylation).18-20 One-pot synthesis (OPS) is a one-step approach, in which SBA-15 is formed and at the same time functionalized by co(9) Zhao, D.; Feng, J.; Huo, Q.; Melosh, N.; Fredrickson, G. H.; Chmelka, B. F.; Stucky, G. D. Science 1998, 279, 548-552. (10) Liu, A. M.; Hidajat, K.; Kawi, S.; Zhao, D. Y. Chem. Commun. 2000, 1145-1146. (11) Kang, T.; Park, Y.; Yi, J. Ind. Eng. Chem. Res. 2004, 43, 14781484. (12) Lei, J.; Fan, J.; Yu, C. Z.; Zhang, L. Y.; Jiang, S. Y.; Tu, B.; Zhao, D. Y. Microporous Mesoporous Mater. 2004, 73, 121-128. (13) Deere, J.; Magner, E.; Wall, J. G.; Hodnett, B. K. Catal. Lett. 2003, 85, 19-23. (14) Vinu, A.; Murugesan, V.; Hartmann, M. J. Phys. Chem. B 2004, 108, 7323-7330. (15) Corriu, R. J. P.; Mehdi, A.; Reye, C.; Thieuleux, C. Chem. Commun. 2002, 1382-1383. (16) Yang, C. M.; Zibrowius, B.; Schuth, F. Chem. Commun. 2003, 1772-1773. (17) Mbaraka, I. K.; Shanks, B. H. J. Catal. 2005, 229, 365-373. (18) Yang, C. M.; Wang, Y. Q.; Zibrowius, B.; Schuth, F. Phys. Chem. Chem. Phys. 2004, 6, 2461-2467. (19) Chang, A. C. C.; Chuang, S. S. C.; Gray, M.; Soong, Y. Energy Fuels 2003, 17, 468-473. (20) Choi, M.; Kleitz, F.; Liu, D. N.; Lee, H. Y.; Ahn, W. S.; Ryoo, R. J. Am. Chem. Soc. 2005, 127, 1924-1932.
10.1021/la051167e CCC: $30.25 © 2005 American Chemical Society Published on Web 09/02/2005
SBA-15 Materials as Carriers for Drug Delivery
Langmuir, Vol. 21, No. 21, 2005 9569
condensation of tetraethyl orthosilicate and triethoxysilane, while, in postsynthesis (PS), the functionalization is accomplished after the formation of stable SBA-15 structures. It would therefore be reasonable to presume that the functionalized SBA-15 synthesized through these two routes may have different surface properties, hence resulting in different applications of the material as hosts for various drugs. However, to our knowledge, there has been no detailed report till now that compares the surface performance of SBA-15 materials functionalized by the above two methods for their application as drug matrixes. In this study, SBA-15 materials were functionalized with amine groups by one-pot synthesis and postsynthesis. The surface physical and chemical properties of materials were investigated by FTIR, XRD, N2 adsorption/desorption analysis, ζ potential measurement, nitrogen element analysis, XPS, and TEM. Ibuprofen (IBU) and bovine serum albumin (BSA), which were respectively selected as nonsteroidal anti-inflammatory and protein model drugs, were loaded onto the SBA-15 materials and in vitro released in the medium of phosphate-buffered saline (PBS). The adsorption capacities and release behaviors of these drugs on SBA-15 materials have been studied, with emphasis on the host (matrix)-guest (drug) interactions which determine the adsorption and release behaviors of drugs. Experimental Section Materials and Synthesis. As-synthesized SBA-15 materials were prepared according to the procedure reported by Zhao et al.,9 using Pluronic 123 triblock polymer [(EO)20(PO)70(EO)20, Mav ) 5800; Aldrich] as a structure-directing agent and tetraethyl orthosilicate (TEOS; Aldrich) as silica source. The molar composition of the mixture was 1SiO2:0.017P123:2.9HCl:202.6H2O. The mixture was first stirred to react at 40 °C for 24 h followed by crystallization at 100 °C for 48 h under static conditions in a polypropylene bottle. All materials were filtered, washed with deionized water, and dried at 60 °C overnight. To prepare functionalized SBA-15 by postsynthesis, the above materials were further calcined to remove the organic template. Then 1.0 g of pure calcined SBA-15 reacted with 3-aminopropyltrimethoxysilane (APTMS; Sigma-Aldrich) in 30 mL of 1,4dioxane (99%, Sigma-Aldrich) under reflux for 24 h. The resultant white solid was filtered off, washed with diethyl ether (3 × 20 cm3, Sigma-Aldrich), and dried under vacuum. Functionalized SBA-15 prepared by one-pot synthesis was carried out using the same procedure as that used in the synthesis of as-synthesized SBA-15 except that APTMS was introduced together with TEOS. The surfactant template was removed by refluxing with ethanol (1 g of sample in 3 × 50 cm3 of ethanol) for 10 h each time. It was reported that a maximum of 70% of the surfactant could be removed by refluxing in ethanol.21 Drug Loading Procedure. To load SBA-15 with IBU (Aldrich), 0.2 g of the powder sample was added to 10 mL of ibuprofen-hexane solution (30 mg/mL) and soaked for 3 days under stirring until the concentration of the solution did not significantly change; this was done by monitoring the ibuprofen concentration using a Shimadzu UV-3101 spectrophotometer at a wavelength of 272 nm. The amount of drug loaded onto the samples was determined according to the change of concentration before and after soaking. The powders were quickly and thoroughly washed with hexane and dried under vacuum. The same procedures were used to load samples with BSA (SigmaAldrich) with a shaker at room temperature, except that BSA was dissolved in phosphate buffer at pH 4.7 and 6.6 and the BSA concentration was measured at a wavelength of 280 nm. After loading, the samples were washed with deionized water and dried. In Vitro Drug Release Studies. The release profiles of model drugs were determined by soaking 0.2 g of sample in 100 mL of PBS (pH 7.4) under stirring at 100 rpm, and the temperature was kept at 37 ( 0.1 °C. Samples of 5 mL were withdrawn at a (21) van Grieken, R.; Calleja, G.; Stucky, G. D.; Melero, J. A.; Garcı´a, R. A.; Iglesias, J. Langmuir 2003, 19, 3966-3973.
Figure 1. FTIR spectra of (a) ethanol-extracted SBA-15, (b) calcined SBA-15, (c) functionalized SBA-15 prepared by onepot synthesis, and (d) functionalized SBA-15 prepared by postsynthesis. predetermined time, replaced by fresh medium, and spectrophotometrically analyzed for IBU at 272 nm and for BSA at 280 nm. Characterization Methods. Nitrogen adsorption/desorption measurements were conducted using Quantachrome Autosorb-1 by N2 physisorption at 77 K. The BET specific surface areas of the samples were calculated in the range of relative pressures between 0.05 and 0.35. The pore size distributions were calculated from the adsorption branch of the isotherm using the thermodynamic-based Barrett-Joyner-Halenda (BJH) method. The total pore volume was determined from the adsorption branch of the N2 isotherm at P/P0 ) 0.95. The FT-IR spectra were collected using a Shimadzu FTIR-8700 with a resolution of 2 cm-1. Ten milligrams of sample was pressed (under a pressure of 1 ton/cm2 for 10 s) into a self-supported wafer 16 mm in diameter. Prior to analysis, the wafer was treated in an in situ quartz cell equipped with CaF2 windows under vacuum (
