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Updated: Aug 16, 2026
Generation of Alginate Microspheres for Biomedical Applications
Published on: August 12, 2012
Fabrication of triple-crosslinked gelatin/alginate hydrogels for controlled release applications
Ke-Han Shen1, Ting-Hsiang Chiu1, Kuang-Chih Teng2
1Institute of Polymer Science and Engineering, National Taiwan University, Taipei 10617, Taiwan.
Abstract:
Hydrogels have been demonstrated as smart drug carriers to recognize the tumor microenvironment for cancer treatment, where the dynamic crosslinks in the hydrogel network contribute to the stimuli-responsive features but also result in poor stability and weak mechanical property of the hydrogels. Here, phenylboronic acid-grafted polyethyleneimine (PBA-PEI)-modified gelatin (PPG) was synthesized to crosslink alginate dialdehyde (ADA) through imine bonds and boronate ester bonds, and then calcium ions (Ca2+) were added to introduce the third calcium-carboxylate crosslinking in the network to form the triple-crosslinked PPG/ADA-Ca2+ hydrogels. Given the three types of dynamic bonds in the network, PPG/ADA-Ca2+ hydrogels possessed a self-healing manner, stimuli-responsiveness, and better mechanical properties compared to single- or double-crosslinked hydrogels. The controlled release capability of PPG/ADA-Ca2+ hydrogels was also demonstrated, showing the encapsulated molecules can be rapidly released from the hydrogel network in the presence of hydrogen peroxide while the release rate can be slowed down at acidic pH. Furthermore, PPG/ADA-Ca2+ hydrogels presented selected cytotoxicity and drug delivery to cancer cells due to the regulated degradation by the cellular microenvironment. Taken together, PPG/ADA-Ca2+ hydrogels have been demonstrated as promising biomaterials with multiple desirable properties and dynamic features to perform controlled molecule release for biomedical applications.
Insights
Triple-crosslinked hydrogels offer enhanced stability and self-healing for smart drug delivery. These advanced biomaterials show controlled release and targeted cancer cell delivery, improving cancer treatment potential.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Cancer Therapeutics
Background:
- Hydrogels are promising drug carriers for cancer treatment, recognizing the tumor microenvironment.
- Dynamic crosslinks in hydrogels offer stimuli-responsiveness but compromise stability and mechanical strength.
- Existing hydrogels require improved properties for effective and stable therapeutic delivery.
Purpose of the Study:
- To develop novel triple-crosslinked hydrogels with enhanced stability, self-healing, and controlled release capabilities.
- To investigate the potential of these hydrogels as smart drug delivery systems for cancer treatment.
- To create a biomaterial that addresses the limitations of traditional stimuli-responsive hydrogels.
Main Methods:
- Synthesis of phenylboronic acid-grafted polyethyleneimine (PBA-PEI)-modified gelatin (PPG).
- Crosslinking of PPG with alginate dialdehyde (ADA) via imine and boronate ester bonds.
- Introduction of a third crosslinking network using calcium ions (Ca2+) to form PPG/ADA-Ca2+ hydrogels.
Main Results:
- The triple-crosslinked PPG/ADA-Ca2+ hydrogels exhibited self-healing properties and improved mechanical strength compared to single- or double-crosslinked counterparts.
- Demonstrated stimuli-responsive controlled release of encapsulated molecules, with rapid release in hydrogen peroxide and slower release at acidic pH.
- Showcased selective cytotoxicity and drug delivery to cancer cells, attributed to regulated degradation within the cellular microenvironment.
Conclusions:
- PPG/ADA-Ca2+ hydrogels represent a significant advancement in biomaterial design for drug delivery.
- The triple-crosslinked network provides a versatile platform with tunable properties for biomedical applications.
- These hydrogels hold promise for developing effective and targeted cancer therapies.
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