Diving into RNAi Therapy: An Inhalable Formulation Based on Lipid-Polymer Hybrid Systems for Pulmonary Delivery of...

Area of Science:

• Biotechnology
• Nanomedicine
• Respiratory Therapeutics

Background:

• Respiratory diseases lack effective targeted therapies.
• RNA interference (RNAi) offers a promising therapeutic strategy.
• Developing efficient pulmonary delivery systems for RNAi is crucial.

Purpose of the Study:

• To develop lipid-polymer hybrid nanoparticles (LPHFNPs) for pulmonary delivery of small interfering RNA (siRNA).
• To evaluate the physicochemical properties, cellular uptake, and gene silencing efficacy of the LPHFNPs@siGFP.
• To assess the impact of spray-drying on nanoparticle aerosolization and therapeutic potential.

Main Methods:

• Synthesis of a novel copolymer for nanoparticle formulation.
• Encapsulation of siRNA targeting green fluorescent protein (siGFP) within LPHFNPs.
• Characterization of nanoparticle size, ζ potential, morphology, and siRNA encapsulation efficiency.
• Evaluation of cellular uptake and gene silencing in GFP-expressing lung cancer cells.
• Spray-drying of LPHFNPs@siGFP with trehalose for pulmonary formulation.

Main Results:

• LPHFNPs@siGFP exhibited a size of ~164 nm, positive ζ potential, and ~99% siRNA encapsulation efficiency.
• High cellular uptake and ~50% gene silencing efficacy were observed in vitro.
• Spray-dried LPHFNPs@siGFP showed ~80% siRNA encapsulation efficiency and excellent aerosolization properties.
• Gene silencing efficacy of spray-dried nanoparticles was comparable to fresh formulations.

Conclusions:

• Developed LPHFNPs are suitable for pulmonary siRNA delivery.
• Spray-drying enhances aerosolization properties while maintaining therapeutic efficacy.
• This formulation holds potential for RNAi-based therapy of respiratory diseases.