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

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.

The effect of alendronate on biomineralization at the bone/implant interface

“…22 In this study, mesoporous titania thin films were deposited onto titanium implants and subsequently loaded with ALN. In previous in vitro and in vivo studies, it has been demonstrated that such mesoporous titania films are wellsuited as carrier frameworks for different substances, such as ALN, raloxifene, and Mg. 13,23,24 In the present study, the influence of ALN on bone mineralization was evaluated both in vitro and in vivo. The in vitro method used was based on simulated body fluid (SBF), which has been developed by Kokubo et al 25 This method has been proved to mimic the in vivo bone mineralization well.…”

Stem cell homing using local delivery of plerixafor and stromal derived growth factor‐1alpha for improved bone regeneration around Ti‐implants

“…, where C is the mass sensitivity constant (17.7 ng⋅Hz −1 ⋅cm −2 ) and n the overtone number (1, 3, 5, and so forth). Prior to analysis, the mesoporous titania matrix was deposited onto Ti QCM‐D sensors (QSX 310, Q‐Sense, Sweden), a methodology proven to result in stable mesoporous thin films . The initial flow in the QCM‐D experiments was pure Milli‐Q H 2 O using a flow rate of 50.0 mL/min until a stable baseline was obtained.…”

“…Prior to analysis, the mesoporous titania matrix was deposited onto Ti QCM-D sensors (QSX 310, Q-Sense, Sweden), a methodology proven to result in stable mesoporous thin films. 30,36,37,[42][43][44][45] The initial flow in the QCM-D experiments was pure Milli-Q H 2 O using a flow rate of 50.0 mL/ min until a stable baseline was obtained. Thereafter, a flow at 50.0 mL/min of either plerixafor (0.4 mg/mL) or SDF-1a (8.0Á10 24 mg/mL) dissolved in water was added to monitor the drug adsorption into the mesoporous film.…”

“…A concentration gradient of signaling molecules to attract stem cells could be achieved by using a local controlled delivery. Promising candidates in this respect are mesoporous materials, which have the ability to serve as nano‐mediated controlled drug delivery systems . Such materials are commonly prepared by the evaporation‐induced self‐assembly (EISA) method to obtain well‐defined and predetermined nano‐features .…”

“…Promising candidates in this respect are mesoporous materials, which have the ability to serve as nano-mediated controlled drug delivery systems. [25][26][27][28][29][30] Such materials are commonly prepared by the evaporationinduced self-assembly (EISA) method to obtain well-defined and predetermined nano-features. [31][32][33][34][35][36] In a previous study, it was demonstrated that mesoporous titania thin films with a pore size of 6 nm served as an excellent drug host for the osteoporosis drugs alendronate and raloxifene, resulting in a superior bone-anchorage in rat tibia.…”