Biomedical Engineering Reference
In-Depth Information
insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), bone morphogenetic
protein-2 (BMP-2), bovine serum albumin (BSA), and lysozyme (LYS) have been investi-
gated as model proteins for the loading and release efficiency from nanotube platforms.
BSA is a large molecule with a net negative charge at neutral pH as opposed to LYS, which
is smaller in size with a net positive charge at neutral pH. Nanotubes can be filled with
BSA and LYS by the simplified lyophilization method. The release characteristics of BSA
and LYS are studied in PBS (pH = 7) and acetate buffer (pH = 4.5). When loaded with 200
to 800 μg of BSA and LYS, approximately 60% to 80% of the protein is retained in the nano-
tubes after washing regardless of the initial loading. As expected, slower and sustained
release from nanotubes takes place. The release curves also suggest that leaching rate of
the positively charged LYS is much slower than that of negatively charged BSA. This is
believed to stem from the difference between the negatively and positively charged pro-
teins interacting with the surface charges of the nanotube interface. There are stronger
electrostatic interactions between the positive charged LYS and negatively charged nano-
tube surface (Popat et al. 2007b).
The release of functional substances using the above method can only be sustained
for h. In order to be clinically useful, drug release from implants should last for days or
weeks. The release rate of drugs can be tailored by changing the length and diameter of
the nanotubes. Using titania nanotubes with variable diameters from 100 to 300 nm and
lengths from 1 μm and 5 μm, paclitaxel (with hydrodynamic radius about 0.5 nm) elution
in PBS at 37 o C from nanotube arrays suggests that the maximum drug release is reached
at approximately 2 weeks. The release of drug as a function of time is presented in Figure
5.13. With the same nanotube pore size, the nanotube length profoundly affects the total
drug elution. The 1-μm-long nanotube holds less than half the amount of drug compared
to a 5-μm-long nanotube. The drug delivery dependence on the nanotube dimensions
shows that the nanotopography of the tubes is directly responsible for the drug elution
behavior. Elution is largely insensitive to the tube diameter, but rather to the total length
of nanotube. Elution measurements of large molecule BSA have been performed and the
results indicate elution durations on the order of months. Larger diameter nanotubes elute
less drug than 100-nm nanotubes with the same length (Peng et al. 2009).
Song et al. (2009) have recently developed an actively controllable drug delivery sys-
tem based on titania nanotubes. The amphiphilic TiO 2 nanotube serves as the controllable
drug release system based on a hydrophobic cap on a hydrophilic titania nanotube. This
6
5
4
d = 100 nm, h = 5 μm
d = 300 nm, h = 5 μm
d = 100 nm, h = 1 μm
Flat Ti
3
2
1
0
0
5
10
15
20
25
Time (days)
FIGURE 5.13
Paclitaxel elutions for nanotube arrays of various dimensions. (From Peng et al., Nano Lett. , 9, 1932-1936, 2009.
With permission.)
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