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Systematic Modification and Evaluation of Enzyme-Loaded Chitosan Nanoparticles
Paulo R Lino1, João Leandro1, Lara Figueiredo1
1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
International Journal of Molecular Sciences
|August 7, 2021
Summary
This study developed a safe and effective nano drug delivery system using chitosan, hyaluronic acid, and cyclodextrins to encapsulate human phenylalanine hydroxylase (hPAH). The system enhances protein stability and activity while demonstrating good biocompatibility for potential therapeutic applications.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Polymeric nanoparticles are crucial for stabilizing proteins in drug formulations.
- Chitosan (CS) is a widely used polysaccharide but can be immunogenic.
- Hyaluronic acid (HA) and cyclodextrins (CDs) offer potential for improving CS-based systems.
Purpose of the Study:
- To develop a biosafe and cytocompatible nano delivery system for human phenylalanine hydroxylase (hPAH).
- To utilize chitosan (CS) modified with hyaluronic acid (HA) and cyclodextrins (CDs) for protein nanoencapsulation.
- To ensure protein stability, enzyme activity, and a safe haemocompatible profile.
Main Methods:
- Ionotropic gelation using tripolyphosphate (TPP) to create CS-based nanoparticles.
- Nanoencapsulation of model human phenylalanine hydroxylase (hPAH).
- Characterization of nanoparticulate systems, including cell internalization studies (HepG2) and haemocompatibility assessment.
Main Results:
- Successfully entrapped hPAH within CS nanoparticles, enhancing protein stability and maintaining enzyme activity.
- Developed a formulation process with strict control.
- Demonstrated internalization of nanoparticles by hepatocytes (HepG2 cell line).
- Confirmed a safe haemocompatible profile with no observed cell toxicity.
Conclusions:
- The developed CS-HA-CD nanoparticles provide an effective and stable delivery system for hPAH.
- The system exhibits excellent biocompatibility, including cytocompatibility and haemocompatibility.
- This approach offers a promising strategy for protein-based therapeutics.
