Development of naked pDNA inhalation powder formulation with high transfection efficiency using hyaluronic acid and phenylalanine as excipients

IF 4.2 2区工程技术 Q2 ENGINEERING, CHEMICAL

Advanced Powder Technology Pub Date : 2025-01-01 DOI:10.1016/j.apt.2024.104750

Takaaki Ito , Tomoyuki Okuda , Seiko Uede , Yuki Kushi , Kohei Tahara , Hirokazu Okamoto

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引用次数: 0

Abstract

Nucleic acid-based inhalational drugs hold great clinical promise, but development has been limited by poor transfection efficiency among other factors. We previously described a plasmid (p)DNA powder without vector (naked pDNA powder) prepared for inhalation by spray-freeze-drying and containing hyaluronic acid (HA) as an excipient that demonstrated high transfection efficiency in the lungs. In the present study, we describe modified formulations in which HA is partially replaced by hydrophobic amino acids to enhance dispersibility in air and HA molecular weight is optimized for greater transfection efficiency. In vivo experiments in mice revealed that L-phenylalanine (Phe) in combination with HA conferred higher transfection efficiency than other hydrophobic amino acids. Furthermore, both in vivo and in vitro assays demonstrated that 50 kDa HA conferred higher transfection efficiency than other molecular weights and that the naked pDNA powder composed of 73% HA (50 kDa) and 25% Phe yielded the highest transfection efficiency among powders investigated. A higher relative Phe ratio enhanced aerosol performance but yielded lower transfection efficiency. This trade-off highlights the importance of comprehensively evaluating inhalational powders for both intrinsic transfection efficiency and aerosol performance.

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来源期刊

Advanced Powder Technology 工程技术-工程：化工

CiteScore

9.50

自引率

7.70%

发文量

424

审稿时长

55 days

期刊介绍： The aim of Advanced Powder Technology is to meet the demand for an international journal that integrates all aspects of science and technology research on powder and particulate materials. The journal fulfills this purpose by publishing original research papers, rapid communications, reviews, and translated articles by prominent researchers worldwide. The editorial work of Advanced Powder Technology, which was founded as the International Journal of the Society of Powder Technology, Japan, is now shared by distinguished board members, who operate in a unique framework designed to respond to the increasing global demand for articles on not only powder and particles, but also on various materials produced from them. Advanced Powder Technology covers various areas, but a discussion of powder and particles is required in articles. Topics include: Production of powder and particulate materials in gases and liquids(nanoparticles, fine ceramics, pharmaceuticals, novel functional materials, etc.); Aerosol and colloidal processing; Powder and particle characterization; Dynamics and phenomena; Calculation and simulation (CFD, DEM, Monte Carlo method, population balance, etc.); Measurement and control of powder processes; Particle modification; Comminution; Powder handling and operations (storage, transport, granulation, separation, fluidization, etc.)