Miktoarm star copolymers from D-(−)-salicin core aggregated into dandelion-like structures as anticancer drug delivery systems: synthesis, self-assembly and drug release

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• 作者：Anna Mielańczyk^a ; Justyna Odrobińska^a ; Sebastian Grządka^a ; Łukasz Mielańczyk^b ; Dorota Neugebauer^a ; ^{dorota.neugebauer@polsl.pl}
• 关键词：Miktoarm star polymers ; Drug-loading ; Drug delivery ; Doxorubicin ; Camptothecin
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 December 2016
• 年：2016
• 卷：515
• 期：1-2
• 页码：515-526
• 全文大小：3611 K
• 卷排序：515

文摘

The β-glucoside-based heterofunctional initiator was used in the synthesis of well-defined eight-armed miktopolymers by sequential ring opening polymerization (ROP) of ε-caprolactone (CL) and atom transfer radical (co)polymerization (ATRP) of methyl methacrylate (MMA) and/or tert-butyl methacrylate (tBMA). Consequently, methacrylic acid (MAA) repeating units were introduced via selective cleavage of pendant tert-butyl protecting groups. Both the amphiphilic copolymers and miktoarm copolymers were self-assembled at 37 °C and pH 7.4. The aggregates of miktoarm polymers were larger than that formed by polymethacrylate homoarm stars (≥250 nm vs ≤200 nm). The critical aggregation concentrations (CAC) of (mikto)stars were relatively low (0.006–0.411 mg/mL) and decreased with the increase in MAA fraction content. Both MAA-based mikto- and homoarmed (co)polymers with shorter arms exhibited lower doxorubicin (DOX) loading capacity, whereas camptothecin (CPT) was encapsulated preferably by miktostars. The kinetic profiles of drug release showed that the rate of release was higher at acidic environment (pH 5.0) than in neutral pH. In the most cases the studied miktopolymer systems demonstrated the well-controlled delivery of the model anticancer drugs, which can be adjusted by structural parameters of polymeric carriers.