Linolenic acid grafted hyaluronan: Process development, structural characterization, biological assessing, and...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery

Background:

• Hyaluronan (HA) is a crucial biomaterial with therapeutic potential.
• Grafting HA with alpha-linolenic acid (αLNA) aims to enhance its properties.
• Unexpected cytotoxicity was observed in the αLNA-HA derivative under specific conditions.

Purpose of the Study:

• To optimize the derivatization of HA with αLNA under mild conditions.
• To investigate and mitigate the cytotoxicity of the αLNA-HA derivative.
• To determine optimal storage conditions for preserving the derivative's stability and beneficial effects.

Main Methods:

• Benzoyl mixed anhydrides methodology for HA derivatization.
• Optimization of reaction and scale-up to semi-production.
• Comparative stability studies of oven-dried, spray-dried, and lyophilized αLNA-HA stored at various temperatures (-20°C, 4°C, 25°C).
• Material characterization using NMR, FTIR, GC-MS, TGA.
• In vitro cytotoxicity assessment on mouse fibroblasts (NIH-3T3).

Main Results:

• The αLNA-HA derivative exhibited unexpected cytotoxicity after oven drying and storage at 40°C.
• Spray-dried αLNA-HA stored at ambient temperature under an inert atmosphere demonstrated the highest stability.
• An inert atmosphere suppressed oxidation of αLNA, supporting positive effects on cell viability.
• The study confirmed the potential of αLNA-HA for encapsulating hydrophobic drugs.

Conclusions:

• Storage conditions significantly impact the stability and bioactivity of αLNA-HA.
• Spray drying combined with storage under an inert atmosphere is recommended for preserving αLNA-HA.
• Preventing αLNA oxidation is crucial for maintaining the derivative's beneficial cellular effects.
• αLNA-HA is a promising material for drug delivery applications.