Chemistry Reference
In-Depth Information
6.5.1 Drug Delivery Systems
Drug delivery by polymers has been considered for targeted drug delivery because
they have an enhanced permeability and retention (EPR) effect [
50
] and reticuloe-
nodothelial system (RES)-avoiding effect [
51
,
52
]. However, new insights have
been obtained from recent studies regarding the intracellular distribution and
efficacy of drug delivery by polymers. For example, triple-labeling confocal
microscopy in live cells revealed the localization of micelles in several cytoplasmic
organelles, including mitochondria, but not in the nucleus. Moreover, micelles of
the medicinal polymer drug delivery system can change the cellular distribution and
increase the amount of agent delivered to the cells [
53
-
55
]. A full-scale study of the
enzyme was carried out from the purified saccharase by the German chemist
Willstatter in 1920. The purified enzyme is thought to consist of active groups of
low and high molecular weight carriers, like saccharase [
56
]. However, it is made
possible for catalytic reaction by the large molecules of the enzyme protein. The
active site is thought to consist of low molecular weight and high molecular weight
carriers, which is the original concept of a supramolecule. DDMC has been obtained
by graft-polymerization of MMA onto DEAE-dextran in water [
7
-
9
]. The resulting
DDMC of hairy nanoparticles have an amphiphilic domain of DEAE-dextran and a
hydrophobic domain of PMMA so as to form a polymer micelle [
21
]. DDMC has a
safe transfection efficacy after autoclaving and is superior to other transfectants as
a non-viral carrier for gene introduction [
23
,
57
-
62
]. On the other hand, paclitaxel
is well known as a strong anticancer agent that can introduce cancer cells to
apoptosis through stabilization of tubulin (i.e., tubulin polymerization).
6.5.2 Preparation of DDMC/PTX Complex
Preparation of DDMC:
Two grams of DEAE-dextran hydrochloride (nitrogen
content 3 %) derived from dextran (
M
w
500,000) was dissolved in 100 mL of
water, followed by the addition of 3.5 mL of MMA. While stirring, the air in the
reaction vessel was fully replaced with N
2
gas. Next, 0.1 g of CAN and 15 mL of
0.1 N nitric acid was added, and the mixture was stirred for 1 h at 30
C. Finally,
3 mL of a 1 % aqueous solution of hydroquinone was added to stop the reaction, and
the resulting DDMC was purified by water dialysis using a cellophane tube to
remove any unreacted MMA, ceric salts and nitric acid.
DDMC-paclitaxel complexation:
The DDMC/PTX complex was obtained by
adding paclitaxel as a guest to 5 mL of 2 % DDMC. Three samples were prepared,
containing 0, 0.385 or 0.709 mg/mL paclitaxel. For all samples, the grafting rate
was 102 % and DDMC concentration was 9.6 mg/mL.
