A smart flower-like polymeric micelle for pH-triggered anticancer drug release.
Novel pH-responsive flower-like micelles were developed to provide the mechanism for pH-triggered drug release from drug carriers. The micelles (particle size: approximately 165 nm; critical micelle concentration (CMC): approximately 4 microg/ml), constructed from poly(N(epsilon)-(3-diethylamino)propyl isothiocyanato-L-lysine)-b-poly(ethylene glycol)-b-poly(L-lactide) [poly(DEAP-Lys)-b-PEG-b-PLLA], were designed to have a self-assembled flower-like arrangement consisting of two hydrophobic blocks [deprotonated poly(DEAP-Lys) block and PLLA block] and a petal-like hydrophilic PEG block at physiological pH. As the pH decreases to slightly acidic pH (<pH 7.0), as in tumor extracellular pH (pH(e)), the flower-like micelles undergo a change in the hydrophobicity of the micellar core. The protonation of poly(DEAP-Lys) changed the physical property of the polymer from hydrophobic to hydrophilic, resulting in disintegration of the micellar core. The co-presence of a pH-insensitive PLLA block in the micellar core affected the protonation of poly(DEAP-Lys), allowing the micelle to be stable at pH 7.0-7.4. In this study using doxorubicin (DOX) as the model drug, DOX release from the micelles accelerated in response to tumor pH(e).
Oh
Kyung Taek
KT
College of Pharmacy, Chung-Ang University, 221 Heukseok dong, Dongjak-gu, Seoul 155-756, South Korea.
Oh
Young Taik
YT
Oh
Nam-Muk
NM
Kim
Kwangmyung
K
Lee
Don Haeng
DH
Lee
Eun Seong
ES
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D004317:Doxorubicin