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Development, Optimization, and Pharmacokinetics Study of Bufalin/Nintedanib Co-loaded Modified Albumin Sub-microparticles Fabricated by Coaxial Electrostatic Spray Technology

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Abstract

Coaxial electrostatic spray technology has received extensive attention in fabricating micro/nanoparticles for drug delivery. However, there are few reports on applying this technology in preparing albumin nanoparticles. In this study, the bufalin (BF) and nintedanib (NDNB) co-loaded ursodeoxycholic acid and p-biguanides benzoic acid decorated albumin sub-microparticles (BN-DUB subMPs) were fabricated by coaxial electrostatic spray technology and optimized by central composite design. Five percent of albumin (contained 0.7% polyethylene oxide) solution was selected as the shell solution which ejected through outer axis with the flow rate of 0.07 mm/min, while the core solution which contained by BF and NDNB ethanol solution was ejected through inner axis with the flow rate of 0.05 mm/min. In vitro cell studies revealed that the modified albumin possessed good biocompatibility. What’s more, the BN-DUB subMPs enhanced the inhibitory effect on the growth of LLC cells efficiently. The pharmacokinetics study showed that the t1/2 and AUC0-t of BN-DUB subMPs increased significantly compared with that of the drug solution, which indicated the improved in vivo stability of modified albumin nanoparticles. Thus, this study provided a novel and simple technical platform for the development of albumin-based drug carriers.

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Funding

This research was supported by the China Postdoctoral Science Foundation (2017M610309, 2019T120403).

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Authors and Affiliations

  1. College of Pharmacy, Jiangsu University, Zhenjiang, 212013, China

    Peng Chen, Shengzhe Lu, Bin Pan & Ying Xu

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  1. Peng Chen
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  2. Shengzhe Lu
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Contributions

Peng Chen: conceptualization, writing — original draft, methodology.

Shengzhe Lu: investigation, validation, data curation.

Bin Pan: formal analysis, writing — reviewing and editing.

Ying Xu: funding acquisition, project administration, supervision, writing — reviewing and editing.

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Correspondence to Ying Xu.

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Chen, P., Lu, S., Pan, B. et al. Development, Optimization, and Pharmacokinetics Study of Bufalin/Nintedanib Co-loaded Modified Albumin Sub-microparticles Fabricated by Coaxial Electrostatic Spray Technology. AAPS PharmSciTech 23, 13 (2022). https://doi.org/10.1208/s12249-021-02163-y

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