Schlosser Corinna S, Morris Christopher J, Brocchini Steve, Williams Gareth R
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Int J Pharm. 2024 Dec 25;667(Pt B):124885. doi: 10.1016/j.ijpharm.2024.124885. Epub 2024 Nov 2.
Electrospraying is a processing technique that has gained much interest to prepare polymeric particles. The technique operates at ambient temperature, thereby avoiding heat induced degradation of labile therapeutics (e.g. peptides and proteins). Exposure to organic solvents can be minimised by co-axial electrospraying through separation of core (aqueous) and shell (organic) solvents. However, aqueous solutions are often difficult to electrospray due to high surface tension. Immiscibility between the core-shell solvents creates a further process challenge. Herein, we describe for the first time the use of hydrophobic ion pairing (HIP) to encapsulate a polypeptide into polymeric particles prepared by co-axial electrospraying. Peptide ion pairs were prepared to incorporate a model peptide - teriparatide - into an organic solvent, permitting facile electrospraying while also protecting the peptide from denaturation. Teriparatide loaded PLGA particles were generated by electrospraying from aqueous or ethanolic peptide solutions (core). A PLGA solution in chloroform (with and without co-solvents) was employed as the shell solution. The aqueous core solution led to a teriparatide encapsulation efficiency of 79.2 ± 19.8 %, which was not significantly different from the ethanolic core (57.1 ± 14.5 %). When aqueous solutions were used the process lacked reproducibility, resulting in low process yields (61.3 ± 4.0 %). In contrast, when an organic core was used a dry powder bed was achieved with a yield of 102.2 ± 8.8 %. The peptide's integrity and biological functionality were retained after electrospraying as ion pairs, as evidenced in a cell-based PTH1 receptor binding assay.
电喷雾是一种制备聚合物颗粒的加工技术，已引起广泛关注。该技术在环境温度下运行，从而避免了热不稳定治疗剂（如肽和蛋白质）的热诱导降解。通过同轴电喷雾分离核心（水性）和外壳（有机）溶剂，可以将有机溶剂暴露降至最低。然而，由于表面张力高，水溶液通常难以进行电喷雾。核壳溶剂之间的不混溶性带来了进一步的工艺挑战。在此，我们首次描述了使用疏水离子对（HIP）将多肽封装到通过同轴电喷雾制备的聚合物颗粒中。制备肽离子对以将模型肽——特立帕肽——掺入有机溶剂中，既便于电喷雾，又能保护肽免于变性。通过从水性或乙醇肽溶液（核心）进行电喷雾生成负载特立帕肽的聚乳酸-羟基乙酸共聚物（PLGA）颗粒。使用氯仿中的PLGA溶液（有和没有共溶剂）作为外壳溶液。水性核心溶液导致特立帕肽的包封效率为79.2±19.8%，与乙醇核心（57.1±14.5%）没有显著差异。当使用水溶液时，该过程缺乏可重复性，导致工艺产率较低（61.3±4.0%）。相比之下，当使用有机核心时，获得了干粉床，产率为102.2±8.8%。如基于细胞的甲状旁腺激素1型（PTH1）受体结合试验所示，电喷雾后作为离子对的肽的完整性和生物学功能得以保留。
