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Purpose <p>This study aims to identify suitable protectants for the freeze-drying of functional peptide-assembled polymer nanoparticles (AsNPs) and polymer nanoparticles (PNPs) composed of methoxy poly(ethylene glycol)-ε-poly(caprolactone) (mPEG-PCL), based on their physicochemical properties and redispersibility after freeze-drying.</p> Methods <p>Nanoparticle suspensions containing various protectants were freeze-dried using a standard freeze dryer. The average hydrodynamic diameter (mean particle size), zeta potential, and polydispersity index of AsNPs and PNPs were measured using dynamic light scattering before and after freeze-drying. Furthermore, the effect of freeze-drying on the oligonucleotide-loading capacity of AsNPs was examined.</p> Results <p>Hydroxypropyl-β-cyclodextrin (HP-β-CD) was identified as an effective protectant for freeze-drying AsNPs and PNPs composed of mPEG (5&#xa0;kDa)-PCL (10&#xa0;kDa). HP-β-CD likely interacts with the polyethylene glycol (PEG) chains of PNPs, preventing aggregation by reducing particle contact during redispersion. The oligonucleotide loading efficiency of AsNPs with a nitrogen-to-phosphate (N/P) ratio of 10 or higher remained comparable to that before freeze-drying.</p> Conclusion <p>HP-β-CD is a promising protectant for the freeze-drying of AsNPs, effectively minimizing nanoparticle aggregation caused by handling or hydrolysis. Therefore, AsNP formulations incorporating HP-β-CD show potential as practical drug delivery system carriers for nucleic acid-based pharmaceuticals.</p> Graphical Abstract <p></p>

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Protectant Selection for Freeze Dry of Functional Peptide-Assembled Polymer Nanoparticles Composed of Methoxy Poly Ethylene Glycol ε-poly Caprolactone as a Carrier of Oligonucleotides

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Shingo Iioka,
  • Yuta Hatanaka,
  • Takayuki Terukina,
  • Takanori Kanazawa,
  • Hiromu Kondo

摘要

Purpose

This study aims to identify suitable protectants for the freeze-drying of functional peptide-assembled polymer nanoparticles (AsNPs) and polymer nanoparticles (PNPs) composed of methoxy poly(ethylene glycol)-ε-poly(caprolactone) (mPEG-PCL), based on their physicochemical properties and redispersibility after freeze-drying.

Methods

Nanoparticle suspensions containing various protectants were freeze-dried using a standard freeze dryer. The average hydrodynamic diameter (mean particle size), zeta potential, and polydispersity index of AsNPs and PNPs were measured using dynamic light scattering before and after freeze-drying. Furthermore, the effect of freeze-drying on the oligonucleotide-loading capacity of AsNPs was examined.

Results

Hydroxypropyl-β-cyclodextrin (HP-β-CD) was identified as an effective protectant for freeze-drying AsNPs and PNPs composed of mPEG (5 kDa)-PCL (10 kDa). HP-β-CD likely interacts with the polyethylene glycol (PEG) chains of PNPs, preventing aggregation by reducing particle contact during redispersion. The oligonucleotide loading efficiency of AsNPs with a nitrogen-to-phosphate (N/P) ratio of 10 or higher remained comparable to that before freeze-drying.

Conclusion

HP-β-CD is a promising protectant for the freeze-drying of AsNPs, effectively minimizing nanoparticle aggregation caused by handling or hydrolysis. Therefore, AsNP formulations incorporating HP-β-CD show potential as practical drug delivery system carriers for nucleic acid-based pharmaceuticals.

Graphical Abstract