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. 2015 Jul 8:10:4425-36.
doi: 10.2147/IJN.S83005. eCollection 2015.

Controlling drug delivery kinetics from mesoporous titania thin films by pore size and surface energy

Johan Karlsson  1 , Saba Atefyekta  1 , Martin Andersson  1
Affiliations

Controlling drug delivery kinetics from mesoporous titania thin films by pore size and surface energy

Johan Karlsson et al. Int J Nanomedicine. .

Abstract

The osseointegration capacity of bone-anchoring implants can be improved by the use of drugs that are administrated by an inbuilt drug delivery system. However, to attain superior control of drug delivery and to have the ability to administer drugs of varying size, including proteins, further material development of drug carriers is needed. Mesoporous materials have shown great potential in drug delivery applications to provide and maintain a drug concentration within the therapeutic window for the desired period of time. Moreover, drug delivery from coatings consisting of mesoporous titania has shown to be promising to improve healing of bone-anchoring implants. Here we report on how the delivery of an osteoporosis drug, alendronate, can be controlled by altering pore size and surface energy of mesoporous titania thin films. The pore size was varied from 3.4 nm to 7.2 nm by the use of different structure-directing templates and addition of a swelling agent. The surface energy was also altered by grafting dimethylsilane to the pore walls. The drug uptake and release profiles were monitored in situ using quartz crystal microbalance with dissipation (QCM-D) and it was shown that both pore size and surface energy had a profound effect on both the adsorption and release kinetics of alendronate. The QCM-D data provided evidence that the drug delivery from mesoporous titania films is controlled by a binding-diffusion mechanism. The yielded knowledge of release kinetics is crucial in order to improve the in vivo tissue response associated to therapeutic treatments.

Keywords: QCM-D; alendronate; controlled drug delivery; mesoporous titania; release kinetics.

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Figures

Figure 1
Figure 1
SEM micrographs of mesoporous titania thin films. Notes: SEM micrographs of mesoporous titania thin films prepared with the following structure-directing agents: (A) CTAB, (B) BRIJ S10, (C) P123, (D) P123 and PPG as swelling agents with a ratio of 1:0.5 (PPG-0.5), and (E) P123 and PPG as a swelling agent with a ratio of 1:1 (PPG-1). Abbreviations: CTAB, cetyltrimethylammonium bromide; PPG, poly(propylene glycol); SEM, scanning electron microscopy.
Figure 2
Figure 2
TEM micrographs of the different prepared mesoporous titania films. Notes: TEM micrographs of the different prepared mesoporous titania films using the following templates: (A) CTAB, (B) BRIJ S10, (C) P123, (D) P123:PPG with a ratio of 1:0.5 (PPG-0.5), and (E) P123:PPG with a ratio of 1:1 (PPG-1). Abbreviations: CTAB, cetyltrimethylammonium bromide; PPG, poly(propylene glycol); TEM, transmission electron microscopy.
Figure 3
Figure 3
SEM images of mesoporous titania film cross-sections coated on glass slides. Notes: Cross-sections of (A) a BRIJ S10 coating and (B) a PPG-0.5 coating are shown. Abbreviations: PPG, poly(propylene glycol); SEM, scanning electron microscopy.
Figure 4
Figure 4
SAXS data for the mesoporous titania films possessing different pore sizes and the nonporous titania. Notes: The peak positions are marked with *. The curves representing the different samples are separated in y-direction to simplify the visual comparison between them. Abbreviation: SAXS, small angle X-ray scattering.
Figure 5
Figure 5
QCM-D results of the adsorption and release of ALN. Notes: The adsorption proceeded until the time point marked with *; thereafter, the surfaces were rinsed with pure water to examine the release rate of ALN. The results are shown for both the unmodified mesoporous titania (A) and for the dimethylsilane treated materials (B) as the mass ALN per coating area (ca). In (C) and (D), the data are recalculated as mass per internal area (ia) for the unmodified and modified coatings, respectively. Abbreviations: ALN, alendronate; QCM-D, quartz crystal microbalance with dissipation.
Figure 6
Figure 6
QCM-D data for the 7.2 nm sample, displaying the different stages of ALN adsorption and release. Notes: In (1), the adsorption kinetics is the rate-limiting factor. In (2), the rate-limiting factor of the adsorption is the diffusion factor. Between (2) and (3), the flow is changed to the rinsing flow, and the initial release (3) is determined by the molecular diffusion. The release becomes thereafter sustained (4) and the rate-limiting step is then the desorption isotherm. Abbreviations: ALN, alendronate; QCM-D, quartz crystal microbalance with dissipation.
Figure 7
Figure 7
The molecular structure and size of the osteoporosis drug alendronate (ALN).
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