Synthesis of mesoporous sodium hyaluronate microspheres via electrostatic spray method

doi:10.5246/jcps.2024.11.071

Journal of Chinese Pharmaceutical Sciences ›› 2024, Vol. 33 ›› Issue (11): 985-1000.DOI: 10.5246/jcps.2024.11.071

• Original articles • Next Articles

Synthesis of mesoporous sodium hyaluronate microspheres via electrostatic spray method

Wei Huang¹, Jie Zhu¹, Yingshu Feng³, Dan Yang⁴, Caleb Kesse Firempong¹, Yang Qu¹, Haibing He⁵^,^*(), Hongfei Liu¹^,²^,⁵^,^*()

¹ College of Pharmacy, Jiangsu University, Zhenjiang 212013, Jiangsu, China
² Jiangsu Sunan Pharmaceutical Industrial Co., LTD, Zhenjiang 212400, Jiangsu, China
³ Zhenjiang Key Laboratory of Functional Chemistry, Institute of Medicine & Chemical Engineering, Zhenjiang College, Zhenjiang 212028, Jiangsu, China
⁴ Yangtze River Pharmaceutical Group Nanjing Hailing Pharmaceutical Company, Nanjing 210046, Jiangsu, China
⁵ Jiangsu Haizhihong Biomedical Co., Ltd, Nantong 226001, Jiangsu, China

Received:2024-02-16 Revised:2024-03-26 Accepted:2024-05-18 Online:2024-12-10 Published:2024-12-10
Contact: Haibing He, Hongfei Liu
Supported by:
The 2023 Nantong Social Livelihood Science and Technology Plan, the 2023 Nantong Jianghai Talents Project, and the 2022 New Drugs and Platform Enhancement Project of the Yangtze Delta Drug Advanced Research Institute. Zhenjiang Science and Technology Project (Grant No. SH2020048), China Postdoctoral Science Foundation (Grant No. 2020M681532), Jiangsu Planned Projects for Postdoctoral Research Funds (Grant No. 2020Z209), and Natural Science Research Projects of Universities in Jiangsu Province (Grant No. 20KJD350001).

Abstract

Abstract:

In the present study, we employed electrostatic spray technology to fabricate mesoporous microspheres containing sodium hyaluronate (SHMM). This approach aimed to overcome a significant challenge in the formulation development process, specifically addressing the limited water-locking ability inherent to the double-helix structure of sodium hyaluronate (SH). Various parameters were systematically investigated, including the solvent employed, concentrations of SH and poly (ethylene oxide), electrospray flow rate, voltage settings, and needle diameter. Through systematic single-factor testing, we identified the optimal formulation process for generating SH microspheres characterized by favorable morphology and particle size. Additionally, a similar single-factor examination focused on the concentration of the pore-forming agent and the drying temperature, leading to the successful production of mesoporous microspheres with discernible pores. The porosity of the three distinct batches of mesoporous microspheres was consistently measured at 20.30% ± 1.51%. Moreover, all these microspheres displayed a negative surface potential when suspended in water, affirming their strong capacity to bind with positively charged protein drugs. These findings underscored the feasibility of drug loading through ion exchange in subsequent stages. Notably, the successful preparation of recombinant human interferon α-2b crosslinked mesoporous microspheres (rhIFN α-2b-SHCMM) was achieved, demonstrating both high entrapment efficiency and an enhanced drug loading capacity.

Key words: Electrostatic spray, Ion exchange technology, Sodium hyaluronate mesoporous microspheres

Supporting:

Wei Huang, Jie Zhu, Yingshu Feng, Dan Yang, Caleb Kesse Firempong, Yang Qu, Haibing He, Hongfei Liu. Synthesis of mesoporous sodium hyaluronate microspheres via electrostatic spray method[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(11): 985-1000.

Figures/Tables 22

Table 1. Single-factor level for the prescription process of SHM.

Table 2. Single-factor level table for the prescription process of SHMM.

Table 3. Effect of CNH4HCO3 on porosity.

Table 4. Effect of drying temperature on porosity.

Table 5. Zeta potential of porous SHMM (n = 3).

Table 6. The porosity of different batches of SHMM.

Table 7. DL and EN of rhIFN α-2b-SHCMM (n = 3).

Table 8. In vitro degradation of SHCMM.

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Synthesis of mesoporous sodium hyaluronate microspheres via electrostatic spray method

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