Leucine Coated Inhalable Insulin and Thymopentin Peptide Powders Produced by Aerosol Flow Reactor Method

Nurcin Ugur, Ville Vartiainen, Luis M. Bimbo, Jouni Hirvonen, Esko I. Kauppinen, Janne Raula

Pulmonary route of drug delivery has been the focus of intense research in order to improve the efficacy of therapeutic peptides both for local and systemic treatment. However, formulation of such inhalable powders is challenging since the peptide may be in inactive conformation due to the thermodynamic effects of particle preparation process. In this research, inhalable insulin and thymopentin peptide powders were prepared by the aerosol flow reactor method from precursor solutions of peptide, trehalose, sodium citrate and leucine for the protection of the labile peptides. Scanning electron microscopy images of inhalable peptide powders showed intact and separated particles with spherical and partly-buckled shapes. Particle size distribution of insulin particles was 1.13 m and thymopentin particles was 0.63 m. Aerosolization of inhalable powders were measured with an inhalation testing device showed that emitted dose (ED) of the insulin powders were 1.9 mg/dose and fine particle fractions (FPF) of the insulin powders were 55-59%. Thymopentin powders exhibited 1.5-1.7 mg/dose of ED and 27-36% of FPF. Additionally, inhalable insulin powders were analysed by circular dichroism after the particle preparation process and results indicated similar -helical conformation which assures the conformational stability of insulin after the aerosol process. Furthermore, high performance liquid chromatography analysis of both thymopentin and insulin powders indicated a similar corresponding solute peak as the pristine samples at the same retention time. Protective encapsulation of peptides was shown to be successful and temperature pulse did not affect the peptide stability. In the near future, cellular interaction, cytocompatibility and drug permeation properties of the peptide powder particles will be investigated.

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