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Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity

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Abstract

Poly(2-oxazoline) (POx) is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto- and hemo-compatibility, and is promising to be used as drug carriers. However, the drug loading capacity (DLC) of POx for many drugs is still low except several hydrophobic ones including paclitaxel (PTX). Herein, we prepared a series of amphiphilic POx block copolymers with various functional groups, and investigated the relationship between functional structures and the DLC. Functional POxs with benzyl, carboxyl, and amino groups in the side-chain were synthesized based on a poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline-co-2-butenyl-2-oxazoline) (PMeOx-P(nBuOx-co-ButenOx), PMBEOx) precursor, followed by click reaction between vinyl and the 2-phenylethanethiol, thioglycolic acid and cysteamine. Using thin-film hydration method, eight commonly used drugs with various characteristics were encapsulated within these functional POx polymers. We found that amine-containing drugs were more easily encapsulated by POx with carboxyl groups, while amine functionalities in POx enhanced the loading capacity of drugs with carboxyl groups. In addition, π-π interactions resulted in enhanced DLC of most drugs, except several hydrophobic drugs with aromatic to total carbon ratios less than 0.5. In general, we could successfully encapsulate all the selected drugs with a DLC% over 10% using properly selected functional POxs. The above results confirm that the DLC of polymeric carriers can be adjusted by modifying the functional groups, and the prepared series of functional POxs provide an option for various drug loadings.

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 51673185, 51973215, 51673189, 51829302, 52003268 and 52025035), as well as the support from the Youth Innovation Promotion Association of Chinese Academy of Sciences (No. 2020232).

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Authors and Affiliations

  1. College of Chemistry, Northeast Normal University, Changchun, 130024, China

    Si Dong & Ming-Xiao Deng

  2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Si Dong, Sheng Ma, Zhi-Lin Liu, Li-Li Ma, Yu Zhang, Zhao-Hui Tang, Ming-Xiao Deng & Wan-Tong Song

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  1. Si Dong
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  2. Sheng Ma
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Correspondence to Ming-Xiao Deng or Wan-Tong Song.

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Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity

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Dong, S., Ma, S., Liu, ZL. et al. Functional Amphiphilic Poly(2-oxazoline) Block Copolymers as Drug Carriers: the Relationship between Structure and Drug Loading Capacity. Chin J Polym Sci 39, 865–873 (2021). https://doi.org/10.1007/s10118-021-2547-6

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