Injectable and Self-Healable pH-Responsive Gelatin-PEG/Laponite Hybrid Hydrogels as Long-Acting Implants for Local Cancer Treatment


Cimen Z., Babadag S., ODABAŞ S., Altuntas S., DEMİREL G. , Demirel G. B.

ACS APPLIED POLYMER MATERIALS, vol.3, no.7, pp.3504-3518, 2021 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 3 Issue: 7
  • Publication Date: 2021
  • Doi Number: 10.1021/acsapm.1c00419
  • Title of Journal : ACS APPLIED POLYMER MATERIALS
  • Page Numbers: pp.3504-3518
  • Keywords: injectable hydrogel, hybrid, laponite, drug delivery, self-healing, NANOCOMPOSITE HYDROGEL, MAGNETIC HYDROGEL, HYALURONIC-ACID, DRUG-DELIVERY, DOXORUBICIN, ALGINATE, EFFICACY, RELEASE

Abstract

Injectable, self-healable, and pH-responsive hybrid hydrogels are highly promising biomaterials for controlled and long-term therapeutic agent release in cancer treatment. Herein, we fabricated an injectable, self-healable, and pH-responsive hybrid hydrogel through the formation of the hydrazone bond between hydrazide-functionalized gelatin (Gel-ADH) and aldehyde-functionalized PEG (diBA-PEG) polymers. During gelation, the resulting pregels were also integrated with laponite (LAP) nanodisks loaded with an anticancer drug, doxorubicin (DOX), yielding to hybrid Gel-ADH/diBA-PEG/LAP@DOX hydrogels. The gelation time of the hybrid hydrogel was observed to be 80 s and the resulting hybrid hydrogels demonstrated excellent injectability and rapid self-healing capability. The gel-sol transition behaviors of hybrid hydrogels indicated an outstanding gelation stability, which is a highly desirable feature in controlled drug delivery application. The injectable hybrid Gel-ADH/diBA-PEG/LAP@DOX hydrogels exhibited a very efficient pH dependent long-term drug release profile. Biocompatibility of the hydrogel components (Gel-ADH, diBA-PEG, and LAP) was also tested using the human breast cell line (SVCT) and endothelial cell line (HUVEC). All components of the hybrid hydrogel possess excellent biocompatibility and even support cell proliferation. Moreover, the cytotoxicity of the hydrogels was investigated on the human breast cancer cell line (MCF-7) and triple-negative breast cancer cell line (MDA-MB-231). Our results clearly suggested that this injectable, self-healable, and pH-responsive hybrid Gel-ADH/diBA-PEG/LAP@DOX hydrogel offers a promising potential as a drug carrier for long-term and controlled release application.