Solid State Sciences 9 (2007) 768e776

www.elsevier.com/locate/ssscie


Bioceramics and pharmaceuticals: A remarkable synergy

Mara Vallet-Reg*, Francisco Balas, Montserrat Colilla, Miguel Manzano

Departamento de Qumica Inorganica y Bioinorganica, Facultad de Farmacia, Universidad Complutense de Madrid,
Pza. Ramon y Cajal s/n, E-28040 Madrid, Spain
Received 23 March 2007; accepted 29 March 2007
Available online 10 April 2007



Abstract

The research on controlled drug delivery systems using bioceramics as host matrices presents two distinct sides; one route ai ms at embedding
pharmaceuticals in biomaterials designed for the reconstruction or regeneration of living tissues, in order to counteract inflammatory responses,
infections, bone carcinomas and so forth, while the other route deals with the more traditional drug introduction systems, i.e. oral administration.
The incorporation of pharmaceuticals to bioceramic matrices could be very interesting in clinical practice. It is rather common in these days
for an orthopedic surgeon working in bone reconstruction to use bioceramics. An added value to the production of these ceramics would be the
optional addition of pharmaceuticals such as antibiotics, anti-inflammatories, anti-carcinogens, etc. In this sense, if we take into account the
infections statistics at hip joint prostheses, the incidence varies between 2 and 4%, reaching up to a 45% in bolts used as external fixation. One
of the main problems in these situations is the access to the infected area of the bone, in order to deliver the adequate antibiotic. If the
pharmaceutical could be included within the implant itself, the added value would be straightforward.
And if the bioceramic is bioactive, and therefore precursor of new bone tissue, the capability to introduce peptides, proteins or growth
factors at its pores could accelerate the bone regeneration processes. We are facing a fine example of multidisciplinary research, where the so-
called transversal supply of knowledge from and between the domains of materials science, biology and medicine will empower the know-how
and applications that shall, undoubtedly, give rise to new advances in science and technology.
2007 Elsevier Masson SAS. All rights reserved.

Keywords: Bioceramics; Ordered mesoporous materials; Drug delivery systems





1. Introduction

Inorganic materials are receiving a great interest in the field of
biomedical science in the last few years. Two main routes have
been traditionally used for drug intake: oral administra-tion and
injection. Traditional therapies are characterized by an increase of
drug concentration in plasma when the intake takes place,
followed by a decrease, leading to a sinusoidal be-havior of the
drug concentration in plasma vs. time (Fig. 1). Inorganic
materials such as bioceramics have been widely in-vestigated to
be used in the development of implants [1e4]. Sometimes, it is
possible to include pharmaceuticals into these ceramics in such a
way that the implant can satisfy its function

* Corresponding author. Tel.: 34 91 394 1843; fax: 34 91 394 1786.
E-mail address: vallet@farm.ucm.es (M. Vallet-Reg).

1293-2558/$ - see front matter 2007 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.solidstatesciences.2007.03.026





of repairing/regenerating the damaged tissue and also locally
protecting the surrounding medium from possible inflamma-
tions and/or infections during the first days after the implanta-
tion [5e8]. Therefore, bioceramics are also useful as drug
delivery systems because of the possibility of drugs confine-
ment and local dosage with the added value of their bone tis-
sue regeneration capability [3]. If the inorganic system
induces the formation of a nano-sized apatite-like layer when
im-mersed into a simulate body fluid, new bone will be
formed [9,10]. The implant macroporosity is a key factor in
tissue en-gineering for both, the oxygenation and
vascularization of liv-ing tissue [11]. Hence, during the
process of formation of apatites over the surface of bioactive
inorganic materials, such as glasses and glass-ceramics,
several porosities can be tailored depending on the
requirements of the new material [12e14].
M. Vallet-Reg et al. / Solid State Sciences 9 (2007) 768e776 769



















Fig. 1. Evolution of drug concentration in plasma vs. time in conventional
ther-apies compared to controlled drug delivery systems.

This bioceramic feature opens the way to use these inor-
ganic materials not only for drug delivery but also for releas-
ing growth factors, proteins, etc. [15] Silica-based ordered
mesoporous materials are possible candidates as reservoir ce-
ramics where drugs can be confined [8,16]. These materials
are characterized by large specific surface areas, ordered pore
systems, and narrow pore size distributions. In addition, these
mesoporous materials have been reported to be excellent
candidates to be used in tissue engineering nanotechnology,
because they show the capability to perform as controlled de-
livery systems of a wide range of drugs [2] and to promote
bone tissue regeneration [17,18].
Ordered mesoporous materials have been extensively re-
ported as drug delivery systems in the last few years (Fig. 2)




























Fig. 2. Statistics on recent publications in silica-based ordered mesoporous
materials as drug delivery systems.

[19e30]. However, there is still a lot of work to do in order to
select the most suitable mesoporous host matrix depending on
the guest molecule to be adsorbed and subsequently re-leased.
The inorganic host system with a given pore structure and
pore size should be designed considering the properties of
such molecule, and this is what the scientific community is
currently demanding. This challenge, extended to the biomed-
ical field, should lead to the development of smart materials,
in which the desired amount of drug delivered for a specific
med-ical treatment could be modulated according to the
patient requirements.
Several key factors should be considered when designing
these systems. The pore size of mesoporous materials to host
the guest drug determines the size of the molecule to be
adsorbed into the mesopores. Thus, the adsorption and re-
lease of molecules in the mesoporous matrix are governed by
size selectivity. Another factor to be considered in the ad-
sorption and release of molecules into mesoporous matrices is
the chemical relationship between both drug molecule and
pore walls. Hence, the appropriate chemical modification of
the silanol groups at the surface of the mesopore walls should
enhance the adsorption and confinement of drug molecules
and it should also allow modulating their release. These two
factors will be considered in the following sections. On the
other hand, as previously reported [17,18,31,32], silica-based
mesoporous materials are bioactive and thus, the combination
of these two properties, bioactivity and controlled drug
delivery, is a remarkable synergy between bioceramics and
pharmaceuticals.

2. Influence of the pore size on the drug adsorption and
release kinetics

The pore diameters and structure of the mesoporous mate-rials
are essentially controlled by the templated synthesis pro-cedure
where a surfactant is used as structure directing agent and then
removed. Although actual pore size determination is still a matter
of debate for some families of mesoporous ma-terials with 3-
dimensional structures (FDU series and SBA-16 materials, where
pore sizes are limited by the sizes of the mi-croporous windows
connecting the spherical mesopores) [33,34], for 2-dimensional
hexagonal structures such as MCM-41 [35] and SBA-15 [36]
materials and 3-dimensional cubic MCM-48 [37] materials, the
pore accessibility is pro-moted for the most common drugs
currently in use. Recently, porous hybrid inorganiceorganic solids
with large pores and unprecedented surface areas have been
developed for applica-tion as drug delivery systems [38]. In
ordered silica mesopo-rous materials, drug molecules are easily
adsorbed by simple diffusion mechanisms without affecting the
chemical nature of the silica on the pore walls, which also
controls the drug re-lease to the environment. The ratio between
the size of the drug and the mesopore diameter is therefore the
governing factor for the diffusion of the molecule through the
mesoporous matrix in both its confinement and subsequent
release.
There are two main ways to investigate the influence of the
pore size on the drug adsorption and release kinetics. The first
770 M. Vallet-Reg et al. / Solid State Sciences 9 (2007) 768e776

approach is to use the same mesoporous structure as host
matrix and vary its pore diameter by employing different syn-
thesis strategies. For instance, to increase the pore size of
MCM-41, different structural directing agents such as surfac-
tants with different alkyl chain lengths, ranging from 12 to 16
carbon atoms, have been employed [8]. Thus, using larger
hydrocarbon chains leaded to greater pore diameters, from 1.8
nm (MCM-41
B
1.8 nm) up to 2.5 nm (MCM-41
B
2.5
nm) (Fig. 3). These systems were investigated as drug de-
livery systems using ibuprofen as a model drug.
The second approach is to compare two structures with sim-
ilar symmetry but very different pore diameters. To illustrate this
example, two 2D hexagonal structured mesoporous mate-rials
with different pore sizes, MCM-41 (B z 3 nm) and SBA-15 (B z
9 nm), were chosen as host matrices. Hence, the pore diameter of
SBA-15 is three times larger than MCM-41. So-dium
alendronate, a bisphosphonate employed in osteoporosis
treatments to inhibit bone resorption by osteoclasts, was se-lected
as guest molecule for this study [30].

2.1. Drug loading

As commented above, ibuprofen was confined into MCM-
41 of different pore diameters. Ibuprofen has a carboxylic
group that would interact with the silanol groups present on
the pore walls. The enlargement of the pore sizes leaded to a
higher ibuprofen load within the pore channels. This fact can
be explained because larger pore sizes could allow a closer
packing of the guest molecules along the pore, and conse-
quently a higher amount of drug would be retained, as graph-
ically shown in Fig. 3 [39]. Consequently, the variation of the
pore size in few nanometer decimals affects the ibuprofen
loading and subsequent release, but new alternatives have to
be explored in order to further control these processes.
The second approach deals with the incorporation of alendr-
onate molecules into MCM-41 and SBA-15 2D mesoporous





















Fig. 3. Ibuprofen adsorption into the pore channels of two MCM-41 structures
with different pore size (1.8 nm and 2.5 nm). At the left bottom corner the
ibuprofen-pore wall interaction is displayed.

matrices. The alendronate molecule possesses phosphonate and
amino groups that can interact with the silanol groups pres-ent in
the pore walls of the mesoporous material, as shown in Fig. 4.
Thus, considering that the pore diameter of the MCM-41
synthesized in this work is 3.8 nm [30] and the alendr-onate
dimensions are 0.61 nm _ 0.55 nm, a possible representa-tion of
these molecules confined into the host matrix is illustrated in Fig.
4. As previously mentioned, the drug adsorp-tion has a strong
dependence on the pore size. SBA-15 possesses a pore diameter
of 9.0 nm, which is considerably greater than MCM-41 (3.8 nm)
and then higher drug loading could be expected due to this large
difference. However, the amount of alendronate loaded is 139
mg/g SiO
2
in MCM-41 and 83 mg/g SiO
2
in SBA-15. Analyzing
these results, it can be observed that the loaded amount of
alendronate is 67% higher in MCM-41 than in SBA-15 (Fig. 4).
Two factors could modulate such be-havior. One factor concerns
to the pore diameter. The higher alendronate loading in MCM-41
compared to SBA-15 could be explained by a diffusion
phenomenon taking place during the alendronate loading process
from aqueous solution. Due to the disproportionate pore diameter
of SBA-15 compared to the molecule to be adsorbed, in this case
alendronate, there would be some of the drug loaded that will be
confined into the large mesoporous, but with no direct interaction
with the pore walls. As a consequence of the absence of any
retaining interaction, this alendronate will be rapidly diffused out
of the pores, leading to equilibrium with the loading solution
during the loading pro-cess. The second factor deals with the
surface area of the meso-porous material. In the case of MCM-41
the surface area is 1157 m
2
/g, while in SBA-15 is 719 m
2
/g and
thus, this differ-ence promotes a higher contact surface of the
drug with the mes-opores wall in the case of MCM-41. This
higher contact surface, which is 67% greater for MCM-41 than
for SBA-15, leads to an increase of the surface to retain the drug,
which produces a larger amount of drug adsorbed, leading to a
67% increase in drug loading (56 mg/g SiO
2
).

The influence of matrix pore diameter vs. guest molecule
size has been also established using the same host matrix
(MCM-41) for 2 different sized drugs: ibuprofen (z1 nm _ 0.5
nm) and alendronate (z0.6 nm _ 0.5 nm). Two main features
have to be considered when comparing such drugs, their
different size and their functional groups. On one hand,
alendronate molecule is 50% smaller than ibuprofen. On the
other hand, ibuprofen posses a carboxylic acid functional
group while alendronate presents phosphonate functional
groups. Despite of its larger size the amount of ibuprofen
adsorbed into unmodified MCM-41 is higher (337 mg IBU/g
mesopo-rous) than alendronate (139 mg AL/g mesoporous).
This fact could be due to the weaker interaction between the
phospho-nate groups and the silanol groups from the pore
walls compared to the carboxylic groups of ibuprofen and
silanol groups.

2.2. Drug delivery

Different kinetics can be found for ibuprofen release depend-
ing on the mesopore diameters. Regarding to the ibuprofen
M. Vallet-Reg et al. / Solid State Sciences 9 (2007) 768e776 771





























Fig. 4. Alendronate adsorption into MCM-41 and SBA-15 mesoporous materials. At the left bottom corner the alendronate-pore wall interaction is displayed.
Inset table: textural data of these mesoporous materials before and after the alendronate loading and drug release data.


release from MCM-41 with different pore sizes, the difference
between MCM-41
B
2.5 nm and MCM-41
B
1.8 nm is a
slightly higher rate of release for the material with the largest
pore diameter during the first day, reaching the value of 68%
at 24 h for MCM-41
B
2.5 nm and 55% at 24 h for MCM-
41
B
1.8 nm.
Alendronate release from MCM-41 (B z 3 nm) and SBA-
15 (B z 9 nm) follows a diffusion mechanism [30]. After 24 h
of essay, the amount of alendronate released from MCM-41 is
80.7 mg/g mesoporous. In the case of SBA-15 the amount of
alendronate released is 45.0 mg/g mesoporous (table in Fig.
4). It can be observed that the percentage of alendronate
released is in the same range (z55%) for both host matrices.
However, it should be noted that SBA-15 induces the partial
retention of alendronate on the silica walls of mesopores. The
presence of microporous connections between adjacent
mesopore channels in SBA-15 may also account for the par-
tial drug retaining [40]. An important conclusion that can be
extracted from the analysis of this illustrative example is that
the relationship between pore and drug sizes is a key factor to
take into account. In the case here described, the alendro-nate
adsorption in SBA-15 shows a pore/drug ratio of ca. 15,
whereas this ratio for the MCM-41 with respect to the same
alendronate is of ca. 6.
The different pore sizes of the host material described in
this work indicates that pore diameter is not a key factor in the
delivery rate, but it is determinant in the drug dosage be-cause
it governs the amount of drug loaded. Thus, it is possible to
control the appropriate dosage for a concrete therapy by
choosing the adequate ratio of pore diameter vs. drug size.


3. Influence of the functionalization

The chemical modification of the surface of mesoporous
materials is a very common strategy for modulating their
prop-erties and performance in the desired conditions. The
literature of mesoporous materials holds a huge amount of
functionali-zation procedures over different inorganic
matrices. Two of the existing functionalization methods are
the co-condensation procedure [41], in which the
functionalizating agent is appro-priately mixed with the silica
precursors and all the procedure is carried out in the same
reaction vessel; and the post-synthe-sis grafting method [42],
where the pure inorganic silica matrix already formed is
reacted with the functionalizating agent usually in anhydrous
conditions to yield silica meso-pores modified with functional
groups with different chemical characteristics. Chemically
grafting functional groups on the ordered mesoporous network
originates a noticeable change in the adsorption characteristics
of the silica surface as well as in its polarity.
The chemical modification of the silanol groups present at
the pore walls has to be selected depending on the chemical
groups of the drug to achieve the desired loading and
releasing performances.

3.1. Functionalization with amino groups

MCM-41 has been functionalized with aminopropyl groups
using the co-condensation (MCM-41eNH
2
eCC) and post-
synthesis (MCM-41eNH
2
ePS) methods [43]. In the table
included in Fig. 5, the values of pore diameter,
772 M. Vallet-Reg et al. / Solid State Sciences 9 (2007) 768e776

























Fig. 5. Scheme of co-condensation and post-synthesis functionalization methods. Inset table: textural properties of MCM-41 before and after amine-functional-
ization and ibuprofen loading, and drug release data.


BET surface area and mesopore volume are shown. It should
be highlighted that the functionalization process always
originates a decrease in the pore diameter, being 2.5 nm in
unmodified MCM-41, 2.2 nm in MCM-41eNH
2
eCC and 1.7
nm in MCM-41eNH
2
ePS materials. The surface area,
calculated using the BET method, and the total pore volume
also experience a reduction when functionalization process
takes place. Therefore, it can be observed that the reduction of
the pore diameter is greater in materials functionalized
through a post-synthesis method than using a co-condensa-
tion process. The amount of silanol groups present in the
resulting materials depends on the method employed for re-
moving the structure directing agents. Calcination, employed
in post-synthesis method described in this work, reduces the
concentration of un-reacted residual alkoxy groups and it also
promotes a further condensation of silanol groups, lead-ing to
an enlargement of the wall thickness. On the other hand, the
solvent extraction, used in the co-condensation method, does
not modify significantly the amount of silanol groups that
were present before the surfactant removal. The comparison
of these two methods leads to materials with quite similar
surface areas but with a greater pore volume re-duction for
post-synthesis functionalized materials than for the co-
condensation modified matrices. As a consequence of this
different pore volume reduction, MCM-41eNH
2
ePS adsorbed
less ibuprofen than MCM-41eNH
2
eCC (table in-serted in Fig.
5).
When further investigating the release kinetics of these
materials, it can be observed that MCM-41eNH
2
eCC has a
delivery rate identical to that of the unmodified MCM-41,
whereas MCM-41eNH
2
ePS material delivers the ibuprofen
three times slower than MCM-41. This different behavior
could be due to the fact that post-synthesis method ensures


that modifying agents are placed in the outer surface of the sil-
ica network, leading to a larger functionalization degree and
consequently to a more effective retention of ibuprofen during
the release process. In fact, whereas MCM-41eNH
2
eCC has
released 275 mg of ibuprofen per gram of mesoporous (ca.
80% of the total load) after 24 h of essay, MCM-41eNH
2
e PS
releases 167 mg IBU/g mesoporous (ca. 60% of the total
load) at the same time (table in Fig. 5). It suggests a relatively
strong interaction between amino groups in MCM-41eNH
2
e
PS and carboxylic groups of ibuprofen. This fact was further
confirmed by
13
C and
1
H NMR spectroscopic studies per-
formed in unmodified MCM-41 and MCM-41eNH
2
ePS sam-
ples loaded with ibuprofen [44], evidencing that there is a
relatively high mobility of ibuprofen molecules in unmodi-
fied MCM-41. It suggests the absence of strong interactions
between the carboxylic groups of ibuprofen and the silanol
groups in the pore walls. This fact could be explained by the
ibuprofen trend to associate forming hydrogen-bonded dim-
mers even into the pore channels of unmodified MCM-41. On
the contrary, when MCM-41 was functionalized with amino
groups, a more restricted mobility of the ibuprofen molecules
was observed, probably due to a stronger attracting interaction
between carboxylic groups of the drug and amino groups
grafted to the pore walls.

3.2. Functionalization with organosilanes
containing different organic groups

The influence of the drugematrix (guestehost) chemical
interaction on the adsorption and delivery rate of ibuprofen in
organically modified MCM-41 has been further investi-gated.
To reach this goal, MCM-41 mesoporous matrices were
functionalized using the post-synthesis method with
M. Vallet-Reg et al. / Solid State Sciences 9 (2007) 768e776 773

organosilanes containing different organic groups [16]: chlor-
opropyl, phenyl, benzyl, mercaptopropyl, cyanopropyl and
bu-tyl, which present comparable lengths. This wide range of
modifications would provide the necessary knowledge to se-
lect the more suitable organic group depending on the drug to
be confined and delivered. As expected, different ibuprofen
adsorption and delivery rates were found depending on the or-
ganic group grafted to the pore walls. Thus, MCM-41 func-
tionalized with polar groups showed a greater ibuprofen
adsorption than MCM-41 functionalized with non-polar
groups [16]. This study evidences the possibility of designing
the host matrix depending on the molecule to be adsorbed and
delivered, and also depending on the dosage and release kinet-
ics desired for a given therapy.

3.3. Loading of alendronate in MCM-41 and
SBA-15 amine-functionalizated host matrices

MCM-41 and SBA-15 were chosen as mesoporous matrices
and alendronate was selected as model drug [30]. The intro-
duction of alendronate in bioceramics seems to be of particular
interest because of the role that this drug plays in bone tissues
inhibiting bone resorption by osteoclasts. Thus, achieving a high
alendronate loading in mesoporous matrices would be aimed if
bone repair is targeted. As mentioned before, a proper
functionalization of the mesopores wall would help to fulfill this
high alendronate loading desired. Alendronate presents 3 de-
protonated oxygens bearing negative charges at the loading pH of
4.8 (the commercial reagent is a sodium salt and

a buffered aqueous solution is used for drug adsorption).
Thus, there would be a strong attracting interaction with pos-
itively charged groups such as amines at this pH.
Fig. 6 shows the N
2
adsorption isotherms of MCM-41 be-
fore and after the alendronate adsorption. In the table inside
Fig. 6, the values of pore diameter, surface area and mes-
oporous volume are shown. It can be observed that the drug
loading reduces the available inner surface of mesopores as
well as the volume of the primary mesopores, those produced
by the template. The mesopore sizes show a similar behavior
as the alendronate adsorption reduces the pore diameter. Un-
modified MCM-41 adsorbed 139 mg of alendronate/g of mes-
oporous material (14%) and such adsorption was favored by
the interaction of the phosphonate groups from alendronate
with the silanol groups present in the pore walls.
N
2
adsorption isotherms of amino functionalized MCM-41
before and after the alendronate adsorption are shown in Fig.
7. Total pore volume, together with the mesopore volume
significantly reduce after the functionalization processes,
which is attributed to the differences in the adsorption charac-
teristics of the amino-grafted surface. Nevertheless, the more
significant change in the isotherms of Fig. 7 is noticed in the
position of the mesopore adsorption leap at lower values of
P/P
0
, i.e. at lower mesopore diameters. This reduction takes
place in an equivalent amount to the length of the grafted ami-
nopropyl chain (ca. 0.82 nm) on the mesopore wall. In addi-
tion, when alendronate is further adsorbed, the mesopore
width is reduced according to the length of the aminopropyl
chains plus that of the alendronate molecule (ca. 0.87 nm)































Fig. 6. N
2
adsorption isotherms of MCM-41 before and after alendronate adsorption. Inset table: textural properties of MCM-41 before and after alendronate
load-ing, and drug release data.
774 M. Vallet-Reg et al. / Solid State Sciences 9 (2007) 768e776































Fig. 7. N
2
adsorption isotherms of amine-functionalized MCM-41 before and after alendronate adsorption. Inset table: textural properties of amine-functionalized
MCM-41 before and after alendronate loading, and drug release data.



(table in Fig. 7). Surface area and mesoporous diameter also
experiences a decrease when functionalization is carried out.
It should be remarked that the functionalization of MCM-41
originates an increase of the drug loading up to 366 mg/g (ca.
37%), which is almost twice the amount adsorbed in un-
modified-MCM 41.
Similar behavior was observed when using SBA-15 (same
hexagonal ordered structure and larger pore diameter) as host
matrix, where alendronate loading was increased from 83
mg/g (8%) in unmodified materials up to 220 mg/g (22%) in
aminopropyl functionalized matrices. In both host matrices
investigated (MCM-41 and SBA-15) the alendronate adsorp-
tion capacity was observed to increase up to almost 3 times
when functionalization of the pore walls was carried out. This
difference can be due to the weaker interaction between the
phosphonate groups of alendronate and the silanol groups
from unmodified-mesoporous material compared to the strong
attracting interaction commented above of the phosphonate
groups and the amine functional groups covering the surface
of the mesopore walls of the modified-mesoporous material
[45].
However, the comparison between both host mesoporous
matrices reveals that amino functionalized MCM-41 adsorbs
more alendronate (336 mg/g) than amino functionalized SBA-
15 (220 mg/g), in the same way that occurred in the case of
these unmodified matrices (Table 1). Again, the larger contact
surface of MCM-41 promotes a higher drug loading



and consequently this confirms the explanation mentioned in
the previous section.

3.4. Delivery of alendronate from MCM-41 and
SBA-15 host matrices

Attending to the kinetics of the release processes from
amine-functionalized materials, it can be observed that the
amount of alendronate delivered after 24 h is 102.9 mg/g in
MCM-41eNH
2
(ca. 76% of the total load). On the other hand,
the amount of alendronate released in SBA-15eNH
2
after 24 h
is 24.2 mg/g (ca. 70% of the load) (Table 1). There-fore, the
percentage of alendronate delivered in amine-functionalized
materials is slightly higher in MCM-41 than in SBA-15.
However, the net dosage is rather higher in the case of
functionalized MCM-41 matrices compared to SBA-15, i.e.
the higher is the loading the higher is the percentage of drug
released to the surrounding medium and consequently, the
higher is the dosage.
One conclusion that can be extracted from these results is that
the modification of the mesoporous matrices with amino groups
clearly allows a greater alendronate adsorption and a better con-
trol over the subsequent drug delivery. This increment on the
drug delivery time in functionalized matrices compared to the
unmodified hosts can be attributed to the greater attracting inter-
action between the phosphonate groups from alendronate and
amino groups from the pore walls. Thus, the drug release would
M. Vallet-Reg et al. / Solid State Sciences 9 (2007) 768e776 775

Table 1
Textural properties of unmodified and amine-functionalized MCM-41 and SBA-15 materials before and after alendronate adsorption, and drug adsorption and
delivery data

























be retarded, and the alendronate delivery would take longer
leading to an increment of the dosage time.

4. Conclusions

Different ordered silica mesoporous systems have been
suc-cessfully employed as matrices to host several
pharmaceutical molecules providing that their size suits to the
pore dimen-sions. However, the adsorbed drug should present
active cen-ters that could interact with the pore walls leading
to drug retention.
Therefore, pore size vs. drug size ratio has been revealed
as an important factor to control the amount of drug to be ad-
sorbed, but it is not as significant in the drug delivery rates. It
has been observed that better control over the drug release
kinetics of these delivery systems has been achieved by mod-
ifying the pore walls of the mesoporous matrices due to the at-
tracting interaction between functional groups from modifying
agents and drugs. Thus, the drug dosage can be modulated de-
pending on the patient requirements, ranging from a range
scale of hours (unmodified matrices) up to a scale of days
(amine-modified matrices).

Acknowledgements

Authors thank the financial support by the Spanish CICYT
(MAT 2005-01486) and CAM (S-0505-MAT-0324) research
projects.

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