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Pharmaceutical Differences Between Block Copolymer Self-Assembled and Cross-Linked Nanoassemblies as Carriers for Tunable Drug Release

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Abstract

Purpose

To identify the effects of cross-linkers and drug-binding linkers on physicochemical and biological properties of polymer nanoassembly drug carriers.

Methods

Four types of polymer nanoassemblies were synthesized from poly(ethylene glycol)-poly(aspartate) [PEG-p(Asp)] block copolymers: self-assembled nanoassemblies (SNAs) and cross-linked nanoassemblies (CNAs) to each of which an anticancer drug doxorubicin (DOX) was loaded by either physical entrapment or chemical conjugation (through acid-sensitive hydrazone linkers).

Results

Drug loading in nanoassemblies was 27 ~ 56% by weight. The particle size of SNA changed after drug and drug-binding linker entrapment (20 ~ 100 nm), whereas CNAs remained 30 ~ 40 nm. Drug release rates were fine-tunable by using amide cross-linkers and hydrazone drug-binding linkers in combination. In vitro cytotoxicity assays using a human lung cancer A549 cell line revealed that DOX-loaded nanoassemblies were equally potent as free DOX with a wide range of drug release half-life (t1/2 = 3.24 ~ 18.48 h, at pH 5.0), but 5 times less effective when t1/2 = 44.52 h.

Conclusion

Nanoassemblies that incorporate cross-linkers and drug-binding linkers in combination have pharmaceutical advantages such as uniform particle size, physicochemical stability, fine-tunable drug release rates, and maximum cytotoxicity of entrapped drug payloads.

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AcknowledgmentS AND DISCLOSURES

This research is supported by the Kentucky Lung Cancer Research Program. Authors thank Alli Eckman for assisting cytotoxicity assays.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky, 40536, USA

    Hyun Jin Lee & Younsoo Bae

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  1. Hyun Jin Lee
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Correspondence to Younsoo Bae.

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Lee, H.J., Bae, Y. Pharmaceutical Differences Between Block Copolymer Self-Assembled and Cross-Linked Nanoassemblies as Carriers for Tunable Drug Release. Pharm Res 30, 478–488 (2013). https://doi.org/10.1007/s11095-012-0893-3

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  • DOI: https://doi.org/10.1007/s11095-012-0893-3

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