A poly(gamma-glutamic acid)-amphiphile complex as a novel nanovehicle for drug delivery system.
Recently, many studies have focused on biomedical and pharmaceutical applications of self-assembled nanoparticles. In addition, several biodegradable nanoparticles have been reported to possess poor dispersion stability and poor size-controllability. However, these nanoparticles require complicated fabrication procedures using synthesis techniques. We developed an efficient method for producing nanoparticles derived from a biological origin of molecule poly(gamma-glutamic acid) (gamma-PGA), a cationic lipid, and doxorubicin (Dox). The complex had a size of 510 nm and was able to encapsulate over 90% of the added Dox. An in vivo assay of antitumor activity demonstrated that the complex had significant antitumor activity in sarcoma 180-bearing mice, and was effectively accumulated in solid tumors based on the EPR effect. The data suggested that this complex is a promising formulation of gamma-PGA for targeted delivery to solid tumors. gamma-PGA-12GP2 complexes may possess several unique advantages, including simplicity of nanoparticle preparation, high drug-carrying capacity, appropriate size to allow deeper penetration based on EPR effect into solid tumors, and lack of necessity to modify the chemical structure of the drugs. These data indicate that the gamma-PGA-12GP2 complexes are potentially useful in cancer chemotherapy.
Akao
Tetsuyuki
T
Biotechnology and Food Research Institute, Fukuoka Industrial Technology Center, Fukuoka, Japan.
Kimura
Taro
T
Hirofuji
Yu-shi
YS
Matsunaga
Katsumasa
K
Imayoshi
Rieko
R
Nagao
Jun-Ichi
J
Cho
Tamaki
T
Matsumoto
Haruhito
H
Ohtono
Sumio
S
Ohno
Jun
J
Taniguchi
Kunihisa
K
Kaminishi
Hidenori
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D008055:Lipids; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D004317:Doxorubicin