Biodegradable amphiphilic copolymer containing nucleobase: synthesis, self-assembly in aqueous solutions, and potential use in controlled drug delivery.
Biodegradable nucleobase-grafted amphiphilic copolymer, the methoxyl poly (ethylene glycol)-b-poly (L-lactide-co-2-methyl-2(3-(2,3-dihydroxylpropylthio) propyloxycarbonyl)-propylene carbonate/1-carboxymethylthymine) (mPEG-b- P(LA-co-MPT)), was synthesized. (1)H NMR titration and FT-IR spectroscopy indicated that the hydrogen-bonding could be formed between mPEG-b-P(LA-co-MPT) and 9-hexadecyladenine (A-C16). The hydrophobic microenvironment of the amphiphilic copolymer can protect the complementary multiple hydrogen bonds between mPEG-b-P(LA-co-MPT) and A-C16 from water effectively. The addition of A-C16 not only lowered the critical aggregation concentration (CAC) of mPEG-b-P(LA-co-MPT)/A-C16 nanoparticles (NPs) in aqueous solution but also induced different morphologies, which can be observed by transmission electron microscopy (TEM). Meanwhile, dynamic light scattering (DLS) and turbidometry was utilized to evaluate the effect of temperature and pH change on the stability of mPEG-b-P(LA-co-MPT)/A-C16 NPs. Cytotoxicity evaluation showed good biocompatibility of the mPEG-b-P(LA-co-MPT)/A-C16 NPs. The in vitro drug release profile showed that with the increase of A-C16 content, the doxorubiucin (DOX) release at pH 7.4 decreased, while the faster release rate was observed with the addition of A-C16 with a pH of 5.0. Importantly, DOX-loaded NPs exerted comparable cytotoxicity against MDA-MB-231 cells. This work provided a new method to stabilize NP structure using hydrogen-bonds and would have the potential to be applied in controlled drug delivery.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Huihui
H
Kuang
Suhong
S
Wu
Zhigang
Z
Xie
Fanbo
F
Meng
Xiabin
X
Jing
Yubin
Y
Huang
D000225:Adenine / Q000031:analogs & derivatives*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000494:pharmacology; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013696:Temperature; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D014867:Water
D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D008823:Micelles; D012996:Solutions; D013501:Surface-Active Agents; D014867:Water; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000225:Adenine; D013941:Thymine