Biomedical Engineering Reference
In-Depth Information
the encapsulated drug. Thus, some areas of applications that have been explored
include bioactive substance delivery and the regulation of enzymatic activity. In
particular, low molecular weight hydrogels have been widely employed in vari-
ous applications [ 40 ]. Cell targeting by the drugs is desirable as it serves to fur-
ther enhance the effectiveness of drug delivery systems. With this, Ikeda et al.
have demonstrated the possibility of incorporating cell sensing and targeting
property into supramolecular hydrogel capsules (SH-capsule) [ 41 ]. By assem-
bling the PSA-cleavable additive with the hydrogen capsule, responsiveness of
SH-capsule to the prostate-specific antigen (PSA) was achieved. This allowed
the SH-capsule to detect the prostate cancer cells through the PSA released from
them, which diffused into the developed capsule to cause cleavage of the addi-
tive. Consequently, the hydrophilic fragment that was released from the cap-
sule could target the prostate cancer cell via a plasma membrane-associated
glycoprotein targeting ligand known as DUPA (2-[3-(1,3-dicarboxypropyl)
ureido]pentanedioic acid), which was previously attached to the fragment. This
success in sensing and targeting the prostate cancer cells can provide valuable
knowledge on the applications of supramolecular hydrogels in regulating the
release of bioactive substances and in tissue engineering. Apart from functioning
as effective drug delivery systems, the numerous properties of the low molecu-
lar weight hydrogels also means that biomaterial can be tailor-made for differ-
ent applications. This was done by Qiu and co-workers, where photo-sensitive
spiropyran, D-Ala-D-Ala (a dipeptide residue which is responsive to the antibi-
otic vancomycin) with D-alanine and 1,3,3-trimethyl-2-methyleneindoline were
assembled [ 42 ]. They found that the hydrogel formed disassembled within 5 min
upon exposure to high-pressure mercury lamp of 500 W with cut-off wavelength
below 400 nm. Addition of vancomycin hydrochloride on the gel surface also
successfully induced the gradual transition from the gel to solution phase. The
lack of the response of hydrogel incorporated with L-Ala-L-Ala to vancomycin
hydrochloride illustrated that the hydrogel has assimilated the specific ligand-
receptor interaction property. Thus, a hydrogel with dual response has been cre-
ated which can provide insight to further development of such hydrogels tailored
to different applications. Low molecular weight hydrogels can also be used as
barriers to control the release of bioactive substances. This was illustrated in the
study done by Komatsu and his co-workers, where they demonstrated that the
phosphate-type hydrogelator formed from HO-(CH 2 ) 8 -Fum-Glu-(O-cyclohexyl) 2
responded to four stimuli: temperature, pH, Ca 2 + and light (Fig. 7 ) [ 43 ]. This
meant that any of the four stimuli was able to cause a gel-sol phase transition
that could control the release of the bioactive substances. This work was also
further extended to the development of four fundamental logic gates (AND, OR,
NAND and NOR) which were intended for regulating the release of these bioac-
tive substances. For instance, the OR logic gate could take inputs from UV light
and heat, and hence the presence of either one would be able to induce the gel-
sol phase transition. Such an invention of intelligent supramolecular soft mate-
rials will be very useful in the applications of environment-sensitive actuators,
tissue engineering and controlled-release systems.
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