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Improved Core Viscosity Achieved by PDLLA10kCo-Incorporation Promoted Drug Loading and Stability of mPEG2k-b-PDLLA2.4k Micelles

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Abstract

Purpose

This study aims to investigate the effect of poly(D, L-lactic acid)10K (PDLLA10K) incorporation on the drug loading and stability of poly(ethylene glycol)2K-block-poly(D, L-lactide)2.4K (mPEG2k-b-PDLLA2.4k) micelles. In addition, a suitable lyophilization protector was screened for this micelle to obtain favorable lyophilized products.

Methods

The incorporation ratios of PDLLA10k were screened based on the particle size and drug loading. The dynamic stability, core viscosity, drug release, stability in albumin, and in vivo pharmacokinetic characteristics of PDLLA10k incorporated micelles were compared with the original micelles. In addition, the particle size variation was used as an indicator to screen the most suitable lyophilization protectant for the micelles. DSC, FTIR, XRD were used to illustrate the mechanism of the lyophilized protectants.

Results

After the incorporation of 5 wt% PDLLA10K, the maximum loading of mPEG2k-b-PDLLA2.4k micelles for TM-2 was increased from 26 wt% to 32 wt%, and the in vivo half-life was increased by 2.25-fold. Various stability of micelles was improved. Also, the micelles with hydroxypropyl-β-cyclodextrin (HP-β-CD) as lyophilization protectants had minimal variation in particle size.

Conclusions

PDLLA10k incorporation can be employed as a strategy to increase the stability of mPEG2k-b-PDLLA2.4k micelles, which can be attributed to the viscosity building effect. HP-β-CD can be used as an effective lyophilization protectant since mPEG and HP-β-CD form the pseudopolyrotaxanesque inclusion complexes.

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ACKNOWLEDGMENTS AND DISCLOSURES

None.

Funding

This work was supported by National Mega-project for Innovative Drugs [No.2019ZX09721001], Liaoning Revitalization Talents Program [XLYC1908031], National Science and Technology Major Project of the Ministry of Science and Technology of China [No.2018ZX09735005], and the Project of Liaoning Provincial Department of Education [2019LQN07], PhD Research Startup Foundation of Liaoning Province [2020BS-128]. National Key R&D Program of China (No. 2020YFE0201700).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, People’s Republic of China

    Chen Guo, Ying Zhang, Haoyang Yuan, Yu Zhang, Haibing He, Jingxin Gou & Xing Tang

  2. School of Functional Food and Wine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, Liaoning, People’s Republic of China

    Tian Yin

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  1. Chen Guo
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Correspondence to Jingxin Gou or Xing Tang.

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Guo, C., Zhang, Y., Yuan, H. et al. Improved Core Viscosity Achieved by PDLLA10kCo-Incorporation Promoted Drug Loading and Stability of mPEG2k-b-PDLLA2.4k Micelles. Pharm Res 39, 369–379 (2022). https://doi.org/10.1007/s11095-022-03174-5

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