Akademik Veri Yönetim Sistemi
10th Pulmonary Drug Delivery Conference, İstanbul, Türkiye, 11 - 13 Haziran 2025, (Yayınlanmadı)
Introduction: Proniosomes are dry powder formulations prepared from non-ionic surfactants and water-soluble carrier particles. When exposed to water or biological fluids, proniosomes are converted into niosomes (1). Proniosomes can enhance pulmonary drug delivery by improving the flow and distribution of drugs (2). This study explores the development of probiotic containing proniosomal dry powder inhaler formulations targeting the lungs using various methods and optimizing aerodynamic particle size.
Materials: L. rhamnosus ATA strain was provided from ATA BIO Technology (Turkiye). DFE Pharma (Germany) supplied inhalation-grade lactose, Lactohale LH300, which served as the water-soluble carrier. Sigma Aldrich (USA) supplied Span 60, a non-ionic surfactant, and Amresco (USA) supplied cholesterol. Sigma Aldrich (USA) also provided magnesium stearate (MgSt) and L-leucine.
Methods: Proniosome formulations containing Lactobacillus rhamnosus ATA were prepared using two different techniques: thin film hydration followed by lyophilization (FL) and thin film hydration followed by spray drying (FS). A Buchi (Switzerland) rotary evaporator was utilized for thin film formation. Lyophilization for the FL method was performed using a Teknosem (Turkey) lyophilizer, whereas spray drying for the FS method employed a Buchi Mini Spray Dryer S-300 (Switzerland). To reduce particle size, ultrasonic bath, vortex mixing, and probe sonication techniques were applied. The resulting dry powder from the FL method was sieved using 200 mesh (77 µm) sieves. Particle size distribution of the proniosomes was analyzed via laser diffraction using a Sympatec Helos H0728 instrument (Germany), with Dv10, Dv50, and Dv90 values recorded. In vitro aerodynamic properties were assessed using a Copley Scientific NGI (UK) in combination with a Breezhaler device (Switzerland).
Results: Based on the NGI results of the placebo formulations, both formulations exhibited an emitted fraction (EF) greater than 50% and a fine particle fraction (FPF) exceeding 15%. Among them, the FS formulation showed superior performance, with an EF of 93.24% and an FPF of 52.93%. Each capsule delivers 10 mg of probiotics per inhalation, corresponding to 8.33×10¹¹ CFU/mL. The FS formulation also demonstrated higher probiotic viability, improved flowability, and better consolidation properties. Furthermore, scanning electron microscopy (SEM) images revealed that the FL formulation displayed more irregular particle shapes, whereas the FS formulation had predominantly spherical particles.
Conclusion: Proniosomal dry powder inhaler (DPI) formulations containing Lactobacillus were developed using two distinct preparation methods. Among them, the FS formulation demonstrated superior performance in terms of probiotic viability, flowability of the dry powder, and particle size distribution. Nonetheless, the FL method presents a feasible alternative approach for DPI development.
Acknowledgements:This study was supported by Ankara University Scientific Research Projects Commission under the grant no: TDK-2024-3297.
References:
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2.Gamal A, Saeed H, Sayed O M, Kharshoum R M, Salem H F (2020). Proniosomal Microcarriers: Impact of Constituents on the Physicochemical Properties of Proniosomes as a New Approach to Enhance Inhalation Efficiency of Dry Powder Inhalers. AAPS PharmSciTech, 21:156.
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