Effect of textural properties on the drug delivery behaviour of nanoporous TiO2 matrices

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Abstract

In this work several nanoporous titania powders have been considered as potential carriers for the sustained release of ibuprofen, used as model drug. The textural features and the physico-chemical nature of the surface carriers have been investigated by means of N2 physisorption measurements and FT-IR analyses. The delivery profiles have been collected in vitro in physiological solution at pH 7.4, maintaining the temperature at 37 °C. It has been possible to observe a close correlation between the drug release kinetic and the textural properties of the carriers, in particular for what concerns their pores dimension. The choice of the proper synthetic approach allows a high control of the properties of the final material and of its behaviour in the drug delivery process that can be controlled to a very high extent.

Research highlights

► Nanoporous TiO2 can be used as matrix for the sustained release of a drug. ► The synthetic procedure strongly affects the physical properties of the matrix. ► A close correlation between the pores dimension of TiO2 and the drug release exists. ► Both the dimension and the unimodal nature of the pores affects the release rate.

Introduction

In recent years controlled drug delivery applications have gained increasing attention and the rapid expansion in the advanced materials and technology has resulted in a remarkable progress in their development. The aim of controlled drug delivery is (i) to administer the requested amount of drug to the relevant sites in the human body and (ii) to regulate the drug delivery profile, in order to obtain the optimal therapeutic benefits as much as possible. The conventional metals, oxides and mixed materials used in the drug/medical devices are generally designed at the nano-scale level. In fact, nanoporous materials and coatings are characterized by large surface area and tuneable pores size; moreover, their surface chemical properties can be manipulated ad hoc to suit the final applications.

In particular, many efforts have been (and are) devoted to the realization of nanostructured materials combining controlled drug delivery properties with the features required by tissue engineering (i.e. design of devices that replace or act as a fraction of the whole biological structure).

These studies deal with either polymeric materials and/or with inorganic oxides, such as nanoporous alumina, porous silicon, nanostructured ceramics and nanostructured TiO2 [1], [2], [3]. Among these systems titanium and TiO2 materials are well known in the biomedical applications since the 1970s for their use as orthopaedic implants. In fact, titanium, titanium based alloys and TiO2 systems are among the most common implant materials (such as cardiovascular stents, joint replacements and dental implants) used in the human body because of their desirable mechanical strength, low density, excellent resistance to corrosion and lack of cytotoxic effects [3], [4], [5]. The addition of controlled drug delivery properties to the well known features of TiO2 could expand its potential applications in the biomedical field, and this represents a very attractive field of research.

Several works concerning the use of TiO2 nanotubes as drug carriers have been published [6], [7], [8]; in particular, Popat et al. [9] have studied and reported the effect of titania nanotubes templates as sustained drug release platforms for the treatment of acute infections arising after orthopaedic implant surgeries. These studies evidenced that titania nanotemplate carriers are not only effective against the bacterial infection but, parallel to this, they exhibit improved osteoblast cell adhesion and growth.

In addition to biocompatibility, another important issue must be considered, i.e. the textural properties of the material. A carrier possessing high surface area, large pore volume and proper pore size is fundamental to ensure the loading of the support with the desired amount of drug, thus increasing its adsorption capacity [10]. Moreover, among the several factors affecting the release profile (i.e. the nature of the carrier, the chemical interactions between the drug and the support, etc.), the pores size dimension hardly affects the performance of a drug delivery system, because it influences the rate by which the drug is released from the matrix [11]. The possibility to tune the pores size distribution of the support then allows a better control of the drug release profile.

Titania nanoporous surfaces are usually prepared either using an anodization method [12] or by employing a block copolymer in combination with a titanium precursor (TiCl4) [13]. Many studies are reported on the design of nanostructured titania or titania-silica biomedical ceramics obtained by the sol–gel method, which is a very attractive technique because it allows a high control of the textural properties of the final products by choosing the proper synthetic conditions; this fact becomes particularly important for the possible use of nanostructured carriers in the drug delivery process.

There are several examples of TiO2, SiO2 and TiO2/SiO2 carriers prepared by the sol–gel approach [14], [15], [16], [17]. Lopez et al. [18] have investigated a sol–gel synthesized nanostructured TiO2 matrix with different channel size as reservoirs for the controlled delivery of Temozolomide, an important drug for the treatment of tumors.

In the light of the remarkable potentialities of TiO2 in the biomedical field, in this work the attention was focused on several TiO2 nanoporous matrices to sustain the release of ibuprofen, used as model drug. A series of commercial titania nano-powders and a TiO2 sample prepared by a sol–gel method were investigated in order to identify the correlation among the synthetic approach, the physico-chemical properties and the drug delivery behaviour.

Section snippets

Materials

Ethanol (Fluka), tris buffered saline (0.2 M TRIS–HCl; 9.0% NaCl; pH 7.5 ± 0.1) (Fluka), hydrochloric acid (Fluka), titanium tetraisopropoxide Ti(OC3H7)4 (Fluka), ibuprofen sodium salt (Aldrich), isopropyl alcohol (Fluka). All reagents have been used as received.

TiO2 powders

Five matrices were selected as potential carriers: four commercial TiO2 powders (P25, Millennium, Mirkat, PC105) and a TiO2 matrix synthesized in our laboratory by a sol–gel approach as briefly described in the following. The Ti(OC3H7)4

Results and discussion

In order to evaluate the possibility of using a TiO2 matrix as carrier to sustain the release of a drug molecule and identify the key factors affecting the delivery behaviour, four commercial TiO2 nano-powders have been selected and tested as carriers for the controlled release of ibuprofen. The matrices were chosen on the basis of their textural properties, i.e. surface area and pores dimension.

The drug was introduced on the matrices by incipient wetness impregnation, an effective and reliable

Conclusions

In this work we have studied a series of nanoporous titania systems as possible carriers to sustain the release of ibuprofen, a well known anti-inflammatory drug.

By a sol–gel approach it is possible to modulate the physico-chemical properties of the matrix as a function of the dimension of the drug, thus controlling the rate of its release. In particular, we have observed a close correlation between the pores dimension of the matrix and the release rate of the embedded drug: it is then possible

Acknowledgement

The authors are indebt with Dr. Nicola Borghetto for the excellent technical assistance.

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