Polymersomes from Polypeptide Containing Triblock Co- and Terpolymers for Drug Delivery against Pancreatic Cancer: Asymmetry of the External Hydrophilic Blocks

• Published in: Macromolecular bioscience Vol. 14; no. 9; pp. 1222 - 1238
• Main Authors: Iatrou, Hermis, Dimas, Konstantinos, Gkikas, Manos, Tsimblouli, Chrisida, Sofianopoulou, Sosanna
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.09.2014; Wiley Subscription Services, Inc
• Subjects: Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Asymmetry; Biocompatibility; Cancer; Cell Line, Tumor; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug Screening Assays, Antitumor; Humans; Hydrochlorides; In vitro testing; Invertebrates; nanoparticles; Nanoparticles - chemistry; nanotechnology; Paclitaxel - chemistry; Paclitaxel - pharmacology; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacology; Polyglutamic Acid - analogs & derivatives; Polyglutamic Acid - chemical synthesis; Polyglutamic Acid - chemistry; Polyglutamic Acid - pharmacology; Polylysine - chemical synthesis; Polylysine - chemistry; Polylysine - pharmacology; Polymers; polymersomes; polypeptides; Surgical implants; Vesicles; nanotechnology; pancreatic cancer; nanoparticles; polymersomes; polypeptides
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201400137

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. Model amphiphilic poly(L‐lysine hydrochloride)‐b‐poly(γ‐benzyl(d7)‐L‐glutamate)‐b‐poly(L‐lysine hydrochloride) and poly(ethylene oxide)‐b‐poly(γ‐benzyl‐L‐glutamate)‐b‐poly(L‐lysine hydrochloride) are synthesized. Both form polymersomes in water and are loaded with doxorubicin or paclitaxel. Due to asymmetry of the hydrophilic blocks, poly(ethylene oxide) is always on the periphery. The loaded polymersomes are tested in vivo and in vitro against human pancreatic cancer cell lines.