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Updated: Jun 29, 2026

A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics
Published on: September 22, 2011
A highly programmable platform for sequential release of protein therapeutics.
Haozheng Wang1, Rui Liu1, Sha Wang1
1Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China. yingguan@nankai.edu.cn yongjunzhang@nankai.edu.cn.
This study introduces a novel drug delivery system for sequential protein release. The system uses calcium carbonate microspheres with tunable tannic acid/polyethylene glycol coatings to control therapeutic protein release timing.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Nanotechnology
Background:
- Sequential release of multiple protein therapeutics is crucial for treating complex diseases.
- Existing drug delivery systems have limitations in controlling the number and timing of protein releases.
- Precisely timed sequential delivery of multiple proteins remains a significant challenge in advanced therapeutics.
Purpose of the Study:
- To develop a novel drug carrier system for precisely controlled sequential release of multiple protein therapeutics.
- To overcome the limitations of current systems in adjusting release intervals and the number of proteins released.
- To demonstrate the efficacy of a new layer-by-layer coating strategy for tunable protein release kinetics.
Main Methods:
- Proteins were encapsulated within calcium carbonate (CaCO3) microspheres.
- Microspheres were coated using layer-by-layer assembly of hydrogen-bonded tannic acid (TA) and polyethylene glycol (PEG) films.
- Sequential release was achieved by varying the thickness of the TA/PEG coatings on different batches of microspheres before mixing.
- In vitro and in vivo studies were conducted to evaluate the release profiles and efficacy.
Main Results:
- The tannic acid/polyethylene glycol coating disintegrates at a constant rate, enabling predictable protein release.
- Lag time for protein release is directly proportional to the thickness of the TA/PEG coating.
- Mixed microspheres with varying coating thicknesses demonstrated sequential protein release in vitro and in vivo.
- The system successfully achieved sequential release of more than three proteins with adjustable time intervals.
Conclusions:
- The developed TA/PEG coated CaCO3 microsphere system offers a versatile platform for controlled sequential protein delivery.
- This approach allows for facile adjustment of release timing and the number of therapeutic proteins delivered.
- The system holds significant potential for advancing combination therapies and treating complex diseases requiring multi-stage interventions.
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