Paclitaxel loaded nano-aggregates based on pH sensitive polyaspartamide amphiphilic graft copolymers.
Polyaspartamide (PASPAM) derivatives grafted with 1-(3-aminopropyl)imidazole (API), O-(2-aminoethyl)-O'-methylpolyethylene glycol (MPEG), and octadecylamine (C18) groups were synthesized and their pH-sensitive structure and Paclitaxel (PTX) load/release properties were investigated. C18/MPEG/API-g-PASPAMs systems synthesized showed a strong pH-dependent phase transition behavior near pH 6.7. Large amount of PTX up to 60-75%, depending on polymer composition, was possibly loaded into the C18/MPEG/API-g-PASPAMs nano-aggregates using a solvent-free protocol. Its pH dependent release pattern was affected correspondingly by the phase transition behavior associated with the composition of graft substituents. The pure C18/MPEG/API-g-PASPAMs systems did not show cell toxicity but the PTX-loaded copolymer systems showed a similar cell toxicity to a Taxol-type PTX. From the in vivo animal study, PTX-loaded nano-aggregates showed the much improved inhibition effect on tumor growth compared to the conventional PTX formulation.
School of Chemical Engineering, Theranostic Macromolecules Research Center, Sungkyunkwan University, Suwon, Kyunggi, Republic of Korea.
Kwangwon
K
Seo
Seung Woo
SW
Chung
Youngro
Y
Byun
Dukjoon
D
Kim
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011108:Polymers; D017239:Paclitaxel