Hyaluronidase Coated Molecular Envelope Technology Nanoparticles Enhance Drug Absorption via the Subcutaneous Route

Area of Science:

• Nanotechnology
• Pharmacology
• Biomedical Engineering

Background:

• Subcutaneous (sc) chemotherapy offers patient and economic advantages over intravenous administration.
• Hydrophobic drugs and limited injection volumes hinder effective sc chemotherapy.
• Novel nanoparticle formulations are needed to overcome these limitations.

Purpose of the Study:

• To develop and optimize hyaluronidase-coated polymeric nanoparticles (NPs) for enhanced subcutaneous delivery of hydrophobic anticancer drugs.
• To evaluate the physicochemical properties, stability, pharmacokinetics, and therapeutic efficacy of these novel NPs.

Main Methods:

• Encapsulation of CUDC-101, a hydrophobic anticancer drug, into Molecular Envelope Technology (MET) NPs.
• Optimization of polymer chemistry, formulation parameters, and hyaluronidase (HYD) coating.
• Assessment of drug loading, colloidal stability, and storage stability.
• Pharmacokinetic studies in rats and efficacy studies in a murine A431 xenograft model.

Main Results:

• Optimized HYD-coated MET-CUDC-101 NPs demonstrated high drug loading and excellent colloidal and storage stability.
• Pharmacokinetic studies showed HYD-coating doubled plasma drug exposure compared to uncoated NPs.
• In vivo studies revealed a significant increase in survival time (43 days vs. 15 days) in tumor-bearing mice treated with HYD-MET-CUDC-101 NPs.

Conclusions:

• Hyaluronidase-coated polymeric nanoparticles effectively enable subcutaneous delivery of hydrophobic drugs.
• This nanotechnology approach improves drug bioavailability and demonstrates significant therapeutic potential in preclinical cancer models.
• HYD-MET-CUDC-101 NPs represent a promising strategy for advancing sc chemotherapy.