Production of paclitaxel-loaded PEG-b-PLA micelles using PEG for drug loading and freeze-drying

October 1, 2022

Abstract

A new approach named PEG-assist is introduced for the production of drug-loaded polymeric micelles. The method is based on the use of PEG as the non-selective solvent for PEG-b-PLA in the fabrication procedure. Both hydration temperature and PEG molecular weight are shown to have a significant effect on the encapsulation efficiency of PTX in PEG4kDab-PLA2kDa micelles. The optimal procedure for fabrication includes the use of PEG1kDa as the solvent at 60 °C, cooling the mixture to 40 °C, hydration at 40 °C, freezing at −80 °C and freeze-drying at −35 °C, 15 Pa. No significant difference (p > 0.05) in PTX encapsulation, average particle size and polydispersity index is observed between the samples before freeze-drying and after reconstitution of the freeze-dried cake. The prepared PTX formulations are stable at room temperature for at least 8 h. Scaling the batch size to 25× leads to no significant change (p > 0.05) in PTX encapsulation, average particle size and polydispersity index. PEG-assist method is applicable to other drugs such as 17-AAG, and copolymers of varied molecular weights. The use of no organic solvent, simplicity, cost-effectiveness, and efficiency makes PEG-assist a very promising approach for large scale production of drug-loaded polymeric micelles.

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  1. Shabatina, T. I., Gromova, Y. A., Vernaya, O. I., Soloviev, A. V., Shabatin, A. V., Morosov, Y. N., Astashova, I. V., & Melnikov, M. Y. (2024). Pharmaceutical Nanoparticles Formation and Their Physico-Chemical and Biomedical Properties. Pharmaceuticals (Basel, Switzerland), 17(5), 587. https://doi.org/10.3390/ph17050587
  2. Mohammadzadeh, M., Zarei, M., Abbasi, H., Webster, T. J., & Beheshtizadeh, N. (2024). Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms. Journal of biological engineering, 18(1), 29. https://doi.org/10.1186/s13036-024-00425-4
  3. Rasoulianboroujeni, M., de Villiers, M. M., & Kwon, G. S. (2023). Entropy-Driven Liquid-Liquid Phase Separation Transition to Polymeric Micelles. The journal of physical chemistry. B, 127(37), 7925–7936. https://doi.org/10.1021/acs.jpcb.3c03854
  4. Tiwari, H., Rai, N., Singh, S., Gupta, P., Verma, A., Singh, A. K., Kajal, Salvi, P., Singh, S. K., & Gautam, V. (2023). Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics. Bioengineering (Basel, Switzerland), 10(7), 760. https://doi.org/10.3390/bioengineering10070760
  5. Vach Agocsova, S., Culenova, M., Birova, I., Omanikova, L., Moncmanova, B., Danisovic, L., Ziaran, S., Bakos, D., & Alexy, P. (2023). Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review. Materials (Basel, Switzerland), 16(12), 4267. https://doi.org/10.3390/ma16124267