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

Low mucus penetration ability and cellular uptake seriously limit the effectiveness of local vaginal drug administration because of the rapid foreign particulate and pathogen removal property of the mucus layer. Our previous work proved that nanoparticles with a highly dense polyethylene glycol (PEG) coating can penetrate mucus rapidly (mucus-penetrating nanoparticles, MPPs) and improve drug distribution and retention at mucosal surfaces. However, the "stealth-effect" of the PEG coating also restricts cellular uptake of MPPs. In this work, we designed pH-responsive mucus-penetrating nanoparticles (pMPPs) with hydrazone bonds as the linker to conjugate a dense PEG surface coating, which enabled the pMPPs to rapidly penetrate through the mucus layer. More importantly, the acidic environment of the vaginal mucus induces slow shedding of the PEG layer, leading to a positive charge exposure to facilitate cellular uptake. Overall, pMPPs demonstrate potential as an effective delivery platform for the prophylactic and therapeutic treatment of female reproductive diseases.

Citation

Yating Zhang, Shenghui Li, Kirsten Loch, Gregg A Duncan, Logan Kaler, Rudra Pangeni, Weipan Peng, Sheng Wang, Xiaoqun Gong, Qingguo Xu. pH-Responsive Mucus-Penetrating Nanoparticles for Enhanced Cellular Internalization by Local Administration in Vaginal Tissue. ACS macro letters. 2023 Apr 18;12(4):446-453

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PMID: 36951898

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