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Cyclodextrins are cyclic oligosaccharides forming molecular
inclusion complexes with a wide range of hydrophobic
molecules. The ability to allocate active molecules
into the oligosaccharide hydrophobic core offers several
opportunities in drug solubility, stability, and bioavailability
optimization (1-3). However, aside from ç-cyclodextrins,
which have been used in parenteral drug
administration, systemic application of natural cyclodextrins,
namely R- and â-cyclodextrins, entails the risk of
toxic effects such as hemolysis and nephrotoxicity
(4-5). Aimed at reducing the toxicity and enhancing the
biopharmaceutical properties of cyclodextrins, semisynthetic
derivatives were prepared by introduction of
hydroxyalkyl or sulfoalkyl functions or by conjugation to
water-soluble polymers (3, 6).
Although cyclodextrins possess interesting properties
for delivery of therapeutics with high pharmacological
activity, low therapeutic index, and poor physicochemical
properties, they cannot be used for active drug targeting
because they are devoid of any specificity for biological
structures. To exploit cyclodextrins as targetable drug
delivery systems, the oligosaccharide structure should be
properly functionalized with targeting moieties such
as peptides, hormones, vitamins, antibody fragments,
etc.
Folic acid is a vitamin that binds selectively the folate
receptor (FR), a glycosylphosphatidylinositol-anchored
cell surface receptor that is overexpressed in many
human tumors, including ovarian, endometrial, colorectal,
breast, lung, renal, neuroendocrine carcinomas, and
brain metastases (7). Upon receptor interaction, the folic
acid-FR complex is taken up by cells and moves through
many organelles involved in endocytic trafficking, providing
for cytosolic disposition (8).
The folate receptor mediated endocytosis was largely
investigated to expand the therapeutic value of drugs by
increasing delivery to the target tissue as well as the
target/nontarget tissue ratio. Examples of targetable drug
delivery carriers functionalized by folic acid conjugation
include radionuclide deferoxamine-folate complexes for
radiopharmaceutical imaging, liposome-folate encapsulated
drugs, liposome-folate encapsulated polylysine-
DNA, cytotoxin-folate conjugates and folic acid decorated
nanoparticles (9-13).
Recently, we synthesized a new targetable drug delivery
system by folic acid conjugation to â-cyclodextrins
through a 700 Da poly(ethylene glycol) (PEG) spacer arm.
Preliminary studies demonstrated that the derivative
possesses suitable properties for drug delivery: high
solubility, ability to form inclusion complexes with few
drug models, and negligible hemolytic activity (14).
In the present study the biological and biopharmaceutical
properties of the new β-cyclodextrin-PEG-folic acid
bioconjugate were investigated. The affinity of the bioconjugate
for the immobilized folate binding protein
(FBP) and for the cell membrane folate receptor was
determined by Biacore and cultured tumor folate receptor
overexpressing KB cells, respectively. The ability of the
conjugate to be taken up by folate receptor overexpressing
and nonexpressing cells was also investigated, and its
intracellular localization was determined.
お礼
分かりやすい説明ありがとうございます。 ～精製しました。と訳していました… なんせ論文を読むのが初めてで(^◇^;) 英語が苦手なのもありますが…（笑） 3-d-old maize seedlings が分からなかったので 文の意味が分かりませんでした… ありがとうございましたｍ(＿ ＿;)ｍ