Improved Core Viscosity Achieved by PDLLA 10k Co-Incorporation Promoted Drug Loading and Stability of mPEG 2k -b-PDLLA 2.4k Micelles

Purpose This study aims to investigate the effect of poly(D, L-lactic acid) 10K (PDLLA 10K ) incorporation on the drug loading and stability of poly(ethylene glycol) 2K -block-poly(D, L-lactide) 2.4K (mPEG 2k -b-PDLLA 2.4k ) micelles. In addition, a suitable lyophilization protector was screened for this micelle to obtain favorable lyophilized products. Methods The incorporation ratios of PDLLA 10k 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 PDLLA 10k 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% PDLLA 10K , the maximum loading of mPEG 2k -b-PDLLA 2.4k 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 PDLLA 10k incorporation can be employed as a strategy to increase the stability of mPEG 2k -b-PDLLA 2.4k 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.