Title : Preparation of uniform hyaluronic acid nanoparticles for biomedical applications
Abstract:
Hyaluronic acid (HA) is a naturally occurring long linear polysaccharide known for its biocompatibility, biodegradability, and non-immunogenicity. Nanoparticles from hyaluronic acid have great potential as drug delivery carriers of chemotherapeutics and other biomolecules. The robustness and reproducibility of the preparation method are essential for the final use of hyaluronic acid nanoparticles (HANPs) in biomedical applications. The nanoparticles also must have a defined size and low polydispersity index. Therefore, the whole preparation process needs to be very well optimized.
Here, we present four validated protocols for the preparation of hyaluronic acid nanoparticles by cross-linking of the linear HA polymer, where four different amine-containing compounds were applied: adipic acid dihydrazide (AAD), bis(3-aminopropyl)amine (BAPA), 2,2′-(ethylenedioxy)bis(ethylamine) (EDBE), and ethylenediamine (EDA). To confirm the reproducibility of the method, the nanoparticles were thoroughly characterized. By these protocols, we were able to prepare nanoparticles of size as follows: HANPs prepared with AAD at around 80 nm, HANPs-BAPA at 120 nm, and HANPs-EDBE and HANPs-EDA at around 110 nm. All with an extremely low polydispersity index (values around 0.3). Additionally, we ensured that hyaluronic acid was not fragmented during the preparation of HANPs. Our experimental data clearly showed that the mere choice of a cross-linking agent significantly affects the size, polydispersity of nanoparticles, and their potential for biomedical use. By dynamic light scattering (DLS) analysis, all nanoparticles were demonstrated as monodisperse and uniform. However, in further characterization, concretely nanoparticle tracking analysis (NTA), HANPs-BAPA, and HANPs-EDA indicated a dichotomy of the samples. Therefore, our results show the inadequacy of using the dynamic light scattering method as the only method for size assessment. The resulting nanoparticles were characterized by nanoparticle tracking analysis, asymmetric flow field fractionation, transmission electron microscopy, Fourier-transform infrared spectroscopy, and multi-parametric surface plasmon resonance (MP-SPR) to ensure complex characterization.
In conclusion, our study offers a tool to produce uniform, fully parametrized, and stable nanoparticles with attested affinity to receptor CD44 for the potential drug delivery for not only chemotherapeutics.
What will audience learn from your presentation?
- Importance of nanotechnology in biomedical applications
- Necessity of complex characterization of new nanomaterials
- Usage of biocompatible and biodegradable polymers (polysaccharides) for the development of new drug delivery carriers
- Possibility of delivering cytotoxic therapeutics directly to the tumor tissue
