Biocompatible and pH-sensitive PEG hydrogels with degradable phosphoester and phosphoamide linkers end-capped with amine for controlled drug delivery

Lidong Zhang; Young-Il Jeong; Sudan Zheng; Sung Il Jang; Hongsuk Suh; Dae Hwan Kang; Il Kim

doi:10.1039/C2PY20755A

Biocompatible and pH-sensitive PEG hydrogels with degradable phosphoester and phosphoamide linkers end-capped with amine for controlled drug delivery

Lidong Zhang,^a Young-Il Jeong,^b Sudan Zheng,^a Sung Il Jang,^a Hongsuk Suh,^c Dae Hwan Kang^b and Il Kim*^a

* Corresponding authors

^a The WCU Center for Synthetic Polymer Bioconjugate Hybrid Materials, Department of Polymer Science and Engineering, Pusan National University, Pusan 609-735, Korea
E-mail: ilkim@pusan.ac.kr
Fax: +82 51-513-7720
Tel: +82 51 510 2466

^b National Research and Development Center for Hepatobiliary Cancer, Pusan National University, Yangsan Hospital, Yangsan 626-870, Korea

^c Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Pusan 609-735, Korea

Abstract

A series of biocompatible poly(ethylene glycol) (PEG) hydrogels that are suitable for a variety of biomedical applications have been presented. The cross-linked, water-swellable and multi-amine-functionalized PEG hydrogels (CWMPHs) with degradable phosphoester and phosphoamide linkages in the backbone were successfully produced by the condensation crosslinking reactions between PEG–O–P(O)Cl₂ with different functionalities and 3-arm-PEG–NH₂ pre-polymers, followed by the chain-terminating amination using propane-1,3-diamine in a one-pot process. The newly invented protocol for the fabrication of PEG hydrogels exhibits promising advantages over prior methods including a short reaction time, mass-production, easy separation, and high yield. The structures of the pre-polymers and CWMPHs were well characterized by FT-IR, ¹H NMR, and solid state ³¹P NMR analyses. The mechanical properties of the CWMPHs measured by a rheometer indicate that both storage modulus (G′) and loss modulus (G′′) increase as the functionality of PEG–O–P(O)Cl₂ increases. All the CWMPHs exhibit pH-sensitive water swellability and degradability at room temperature, so that they show a higher water swelling ratio and faster degradation under acidic conditions via an activated cleavage of P–O and P–N bonds. The non-hemolytic property and reasonable biocompatibility of the CWMPHs were proven by in vivo histological assays and in vitro cell viability tests using 293T and HCT-116 cells. We have also demonstrated promising positive results for the use of CWMPHs as a sustained drug delivery system, by mounting an anticancer drug – doxorubicin in vitro, with specifically enhanced release at a low pH 4.0.

Polymer Chemistry

Biocompatible and pH-sensitive PEG hydrogels with degradable phosphoester and phosphoamide linkers end-capped with amine for controlled drug delivery

Abstract

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Biocompatible and pH-sensitive PEG hydrogels with degradable phosphoester and phosphoamide linkers end-capped with amine for controlled drug delivery

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