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Recent advances in ceramic implants as drug delivery systems for biomedical applications.

Colilla M, Manzano M, Vallet-Regí M - Int J Nanomedicine (2008)

Bottom Line: Second, their capability of acting as delivery systems of a large variety of biologically active molecules, including drugs to treat bone infection, inflammation or diseases, and molecules that promote bone tissue regeneration, such as peptides, proteins, growth factors, and other osteogenic agents.The recent chemical and technological advances in the nanometer scale has allowed the design of mesoporous silicas with tailored structural and textural properties aimed at achieving a better control over molecule loading and release kinetics.Moreover organic modification of mesoporous silica walls has been revealed as a key strategy to modulate molecule adsorption and delivery rates.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.

ABSTRACT
Research in the development of new bioceramics with local drug delivery capability for bone regeneration technologies is receiving great interest by the scientific biomedical community. Among bioceramics, silica-based ordered mesoporous materials are excellent candidates as bone implants due to two main reasons: first, the bioactive behavior of such materials in contact with simulated body fluids, ie, a carbonate hydroxyapatite similar to the mineral phase of bone is formed onto the materials surfaces. Second, their capability of acting as delivery systems of a large variety of biologically active molecules, including drugs to treat bone infection, inflammation or diseases, and molecules that promote bone tissue regeneration, such as peptides, proteins, growth factors, and other osteogenic agents. The recent chemical and technological advances in the nanometer scale has allowed the design of mesoporous silicas with tailored structural and textural properties aimed at achieving a better control over molecule loading and release kinetics. Moreover organic modification of mesoporous silica walls has been revealed as a key strategy to modulate molecule adsorption and delivery rates.

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a) Amount of BSA loaded (%) and b) BSA delivery profiles for SBA-15 and MCF mesoporous matrices before and after functionalization using amino groups.
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f7-ijn-3-403: a) Amount of BSA loaded (%) and b) BSA delivery profiles for SBA-15 and MCF mesoporous matrices before and after functionalization using amino groups.

Mentions: Recently, in an effort to promote the loading of large biomolecules, mesostructured cellular foams (mesocellular foams, MCFs) have been employed as host matrices for the adsorption of different enzymes and proteins (Han et al 1999; Zhang et al 2007). The synthesis of MCFs type materials is carried out by employing triblock copolymers and introducing a swelling agent, such as 1,3,5-trimethylbenzene (TMB) into the structure directing template (Schmidt-Winkel et al 1999). TEM images of MCF compared to MCM-41 and SBA-15 mesoporous materials are displayed in Figure 6. The characteristic two-dimensional hexagonal arrays of pores of MCM-41 and SBA-15 mesoporous matrices can be observed. Moreover, MCF exhibits three-dimensional, continuous, ultra-large pore mesoporous structures with large spherical cells interconnected by uniform windows (see arrows in Figure 6). N2 adsorption measurements revealed that MCM-41 and SBA-15 mesoporous materials exhibit type IV isotherms, typical of ordered mesoporous materials. The shape of the hysteresis loops points to cylindrical mesopores with very narrow pore size distributions (Figure 6) (Gregg et al 1982). In the case of MCFs, the sharp rise in the adsorption/desorption isotherms at relative pressures close to 1 points to the existence of large mesopores in these materials (Gregg et al 1982). Pore size distributions of different mesoporous matrices are also shown in Figure 6. The pore diameter of MCM-41 and SBA-15 materials are ca 3 and 9 nm, respectively. MCF presents spherical cells of ca 28 nm with windows of ca 18. The diameter of spherical cells and windows can be modulated by adjusting the amount of swelling agents and the synthesis temperature (Schmidt-Winkel et al 1999). When the confinement of large-size BSA is targeted, mesoporous matrices exhibiting large pore diameters are needed. Thus, SBA-15 and MCF before and after functionalization using amino groups where tested as delivery systems for BSA. The amount of BSA loaded in MCF materials was higher (24%) than in SBA-15 matrices (15%), due to the higher pore volume in the former (Table 3). It should be highlighted that the surface area is not the determinant factor that governs protein adsorption, because it exhibits the opposite trend to protein loading (Table 3). The amount of BSA loaded after functionalization followed the same trend that unmodified materials, ie, MCF-NH2 loaded more BSA (27%) than SBA-15-NH2 (10%), as a result of the higher pore volume of the former. The increase in BSA loading after functionalization of MCF matrix can be attributed to the higher attracting electrostatic interactions of amino groups with the amide groups of protein. However, as it was previously mentioned, organic functionalization always leads to a decrease in pore diameter (Table 3). The pore diameter of SBA-15 (8.5 nm) is just on the limit of BSA size and therefore, after functionalization the pore diameter decreased to 6.9 nm and consequently, a decrease in the amount of BSA adsorbed was observed. On the other hand, organic functionalization with amino groups strongly influenced the BSA release kinetics. As it can be observed in Figure 7, unmodified matrices exhibited an initial burst effect when almost 60% of the protein was quickly released to the delivery medium and then the loaded protein was delivered in a controlled fashion. On the contrary, the initial burst in amino-modified matrices was drastically reduced to ca 10%, and more than 80% of the loaded BSA was released to the medium in a sustained manner. After 24 h of assay, 74% of the total BSA loaded in SBA-15 was released to the medium, whereas after the same time only 27% was released to the medium from SBA-15-NH2 matrix. Moreover, after 24 h of delivery test 62% of the loaded BSA was released from unmodified MCF material and this percentage decreased to 22% after functionalization with amino groups. This research work demonstrates that BSA can be successfully adsorbed into large-volume mesoporous matrices exhibiting the appropriate pore diameter to allow protein confinement. Therefore, when the loading of large-size and large-volume biologically active molecules is targeted, pore diameter acts as the limiting factor and pore volume determines the amount of molecule hosted.


Recent advances in ceramic implants as drug delivery systems for biomedical applications.

Colilla M, Manzano M, Vallet-Regí M - Int J Nanomedicine (2008)

a) Amount of BSA loaded (%) and b) BSA delivery profiles for SBA-15 and MCF mesoporous matrices before and after functionalization using amino groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2636592&req=5

f7-ijn-3-403: a) Amount of BSA loaded (%) and b) BSA delivery profiles for SBA-15 and MCF mesoporous matrices before and after functionalization using amino groups.
Mentions: Recently, in an effort to promote the loading of large biomolecules, mesostructured cellular foams (mesocellular foams, MCFs) have been employed as host matrices for the adsorption of different enzymes and proteins (Han et al 1999; Zhang et al 2007). The synthesis of MCFs type materials is carried out by employing triblock copolymers and introducing a swelling agent, such as 1,3,5-trimethylbenzene (TMB) into the structure directing template (Schmidt-Winkel et al 1999). TEM images of MCF compared to MCM-41 and SBA-15 mesoporous materials are displayed in Figure 6. The characteristic two-dimensional hexagonal arrays of pores of MCM-41 and SBA-15 mesoporous matrices can be observed. Moreover, MCF exhibits three-dimensional, continuous, ultra-large pore mesoporous structures with large spherical cells interconnected by uniform windows (see arrows in Figure 6). N2 adsorption measurements revealed that MCM-41 and SBA-15 mesoporous materials exhibit type IV isotherms, typical of ordered mesoporous materials. The shape of the hysteresis loops points to cylindrical mesopores with very narrow pore size distributions (Figure 6) (Gregg et al 1982). In the case of MCFs, the sharp rise in the adsorption/desorption isotherms at relative pressures close to 1 points to the existence of large mesopores in these materials (Gregg et al 1982). Pore size distributions of different mesoporous matrices are also shown in Figure 6. The pore diameter of MCM-41 and SBA-15 materials are ca 3 and 9 nm, respectively. MCF presents spherical cells of ca 28 nm with windows of ca 18. The diameter of spherical cells and windows can be modulated by adjusting the amount of swelling agents and the synthesis temperature (Schmidt-Winkel et al 1999). When the confinement of large-size BSA is targeted, mesoporous matrices exhibiting large pore diameters are needed. Thus, SBA-15 and MCF before and after functionalization using amino groups where tested as delivery systems for BSA. The amount of BSA loaded in MCF materials was higher (24%) than in SBA-15 matrices (15%), due to the higher pore volume in the former (Table 3). It should be highlighted that the surface area is not the determinant factor that governs protein adsorption, because it exhibits the opposite trend to protein loading (Table 3). The amount of BSA loaded after functionalization followed the same trend that unmodified materials, ie, MCF-NH2 loaded more BSA (27%) than SBA-15-NH2 (10%), as a result of the higher pore volume of the former. The increase in BSA loading after functionalization of MCF matrix can be attributed to the higher attracting electrostatic interactions of amino groups with the amide groups of protein. However, as it was previously mentioned, organic functionalization always leads to a decrease in pore diameter (Table 3). The pore diameter of SBA-15 (8.5 nm) is just on the limit of BSA size and therefore, after functionalization the pore diameter decreased to 6.9 nm and consequently, a decrease in the amount of BSA adsorbed was observed. On the other hand, organic functionalization with amino groups strongly influenced the BSA release kinetics. As it can be observed in Figure 7, unmodified matrices exhibited an initial burst effect when almost 60% of the protein was quickly released to the delivery medium and then the loaded protein was delivered in a controlled fashion. On the contrary, the initial burst in amino-modified matrices was drastically reduced to ca 10%, and more than 80% of the loaded BSA was released to the medium in a sustained manner. After 24 h of assay, 74% of the total BSA loaded in SBA-15 was released to the medium, whereas after the same time only 27% was released to the medium from SBA-15-NH2 matrix. Moreover, after 24 h of delivery test 62% of the loaded BSA was released from unmodified MCF material and this percentage decreased to 22% after functionalization with amino groups. This research work demonstrates that BSA can be successfully adsorbed into large-volume mesoporous matrices exhibiting the appropriate pore diameter to allow protein confinement. Therefore, when the loading of large-size and large-volume biologically active molecules is targeted, pore diameter acts as the limiting factor and pore volume determines the amount of molecule hosted.

Bottom Line: Second, their capability of acting as delivery systems of a large variety of biologically active molecules, including drugs to treat bone infection, inflammation or diseases, and molecules that promote bone tissue regeneration, such as peptides, proteins, growth factors, and other osteogenic agents.The recent chemical and technological advances in the nanometer scale has allowed the design of mesoporous silicas with tailored structural and textural properties aimed at achieving a better control over molecule loading and release kinetics.Moreover organic modification of mesoporous silica walls has been revealed as a key strategy to modulate molecule adsorption and delivery rates.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.

ABSTRACT
Research in the development of new bioceramics with local drug delivery capability for bone regeneration technologies is receiving great interest by the scientific biomedical community. Among bioceramics, silica-based ordered mesoporous materials are excellent candidates as bone implants due to two main reasons: first, the bioactive behavior of such materials in contact with simulated body fluids, ie, a carbonate hydroxyapatite similar to the mineral phase of bone is formed onto the materials surfaces. Second, their capability of acting as delivery systems of a large variety of biologically active molecules, including drugs to treat bone infection, inflammation or diseases, and molecules that promote bone tissue regeneration, such as peptides, proteins, growth factors, and other osteogenic agents. The recent chemical and technological advances in the nanometer scale has allowed the design of mesoporous silicas with tailored structural and textural properties aimed at achieving a better control over molecule loading and release kinetics. Moreover organic modification of mesoporous silica walls has been revealed as a key strategy to modulate molecule adsorption and delivery rates.

Show MeSH
Related in: MedlinePlus