pH-Responsive Mucus-Penetrating Nanoparticles for Enhanced Cellular Internalization by Local Administration in...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• Vaginal drug delivery is hindered by mucus's rapid clearance and low penetration.
• Conventional nanoparticles with polyethylene glycol (PEG) coatings penetrate mucus but have limited cellular uptake.
• Mucus-penetrating nanoparticles (MPPs) improve drug distribution but face cellular uptake challenges.

Purpose of the Study:

• To design pH-responsive mucus-penetrating nanoparticles (pMPPs) for improved vaginal drug delivery.
• To enhance both mucus penetration and cellular uptake of nanoparticles in the vaginal environment.
• To develop a novel nanoparticle platform for prophylactic and therapeutic treatment of female reproductive diseases.

Main Methods:

• Conjugation of a dense PEG surface coating to nanoparticles using pH-sensitive hydrazone linkers.
• Evaluation of nanoparticle mucus penetration ability in vitro.
• Assessment of PEG layer shedding and cellular uptake in acidic vaginal conditions.
• Characterization of pMPPs for potential application in female reproductive health.

Main Results:

• pMPPs demonstrated rapid penetration through the mucus layer.
• The acidic vaginal environment triggered slow shedding of the PEG layer.
• Exposed positive charges on pMPPs facilitated enhanced cellular uptake.
• pMPPs showed potential for improved drug distribution and retention in vaginal tissues.

Conclusions:

• pH-responsive mucus-penetrating nanoparticles (pMPPs) offer a dual advantage of mucus penetration and enhanced cellular uptake.
• The pH-triggered PEG shedding mechanism is key to overcoming the limitations of traditional MPPs.
• pMPPs represent a promising nanodelivery system for vaginal applications, potentially improving treatment outcomes for reproductive diseases.