Hyaluronated nanoparticles with pH- and enzyme-responsive drug release properties

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Developing targeted drug delivery systems is crucial for improving therapeutic efficacy.
• pH-responsive materials offer potential for controlled drug release in specific physiological conditions.
• Hyaluronic acid (HA) is a biocompatible polymer with potential for drug delivery applications.

Purpose of the Study:

• To develop and characterize novel pH-responsive nanoparticles based on hyaluronic acid (HA) grafted with 3-diethylaminopropyl (DEAP) groups (HA-g-DEAP).
• To investigate the pH-dependent drug release characteristics of the HA-g-DEAP nanoparticles.
• To evaluate the synergistic effect of acidic pH and hyaluronidase (Hyal) on drug release.

Main Methods:

• Synthesis of HA-g-DEAP via conjugation of HA carboxylic acid groups and DEAP amine groups.
• Fabrication of nanoparticles through self-assembly of hydrophilic HA and hydrophobic DEAP blocks at pH 7.4.
• Assessment of nanoparticle properties and drug (doxorubicin, DOX) release profiles under varying pH conditions (pH 7.4 and pH 5.0) and in the presence of hyaluronidase (Hyal).

Main Results:

• HA-g-DEAP nanoparticles were successfully synthesized and demonstrated pH-dependent behavior.
• Nanoparticle destabilization and significant doxorubicin (DOX) release were observed at acidic pH (5.0) due to DEAP protonation.
• Hyaluronidase (Hyal) degradation of HA further accelerated DOX release, particularly at acidic pH.

Conclusions:

• HA-g-DEAP nanoparticles represent a promising pH-responsive drug delivery system.
• The system enables controlled drug release triggered by acidic environments and enzymatic activity, relevant for intracellular drug delivery.
• This dual-triggered release mechanism offers potential for enhanced therapeutic outcomes in diseases characterized by acidic microenvironments and hyaluronidase presence.