Polymersomes from polypeptide containing triblock Co- and terpolymers for drug delivery against pancreatic cancer: asymmetry of the external hydrophilic blocks.
Well-defined amphiphilic polymers of the ABA and ABC type are synthesized, where A is poly(L-lysine hydrochloride) (PLL), B is poly(γ-benzyl-(d7) L-glutamate) (PBLG(-d7)), and C is poly(ethylene oxide) (PEO). The two polymers exhibit similar PBLG(-d7) composition, while in the ABC, the volume fraction of PEO block is higher than that of PLL. Both polymers form polymersomes in water. The polymersomes are loaded with doxorubicin or paclitaxel. It is found that in the ABC, due to asymmetry of the two hydrophilic blocks, PEO is always on the outer periphery and the dimensions of the vesicles are smaller. The release of the vesicles is temperature- and pH-dependent. In vivo toxicity tests of the empty vesicles show that they are not toxic. In vitro activity of the loaded vesicles against human pancreatic cancer cell lines reveals comparable activity to Myocet for the ABA loaded with doxorubicin, while lower activity is observed for the ABC.
University of Athens, Chemistry Department, Panepistimiopolis, Zografou, 15771, Athens, Greece.
Hermis
H
Iatrou
Konstantinos
K
Dimas
Manos
M
Gkikas
Chrisida
C
Tsimblouli
Sosanna
S
Sofianopoulou
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; C003172:poly-gamma-benzyl-L-glutamate; D011107:Polylysine; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel
nanoparticles; nanotechnology; pancreatic cancer; polymersomes; polypeptides