Dry Powder Inhalers for Delivery of Synthetic Biomolecules

Abstract

This manuscript provides a comprehensive review of advancements in dry powder inhaler (DPI) technology for pulmonary and systemic drug delivery, focusing on proteins, peptides, nucleic acids, and small molecules. Innovations in spray-drying (SD), spray freeze-drying (SFD), and nanocarrier engineering have led to enhanced stability, bioactivity, and aerosol performance. Studies reveal the critical role of excipients, particle morphology, and device design in optimizing deposition and therapeutic efficacy. Applications include asthma, cystic fibrosis, tuberculosis (TB), and lung cancer, with emerging platforms such as ternary formulations and siRNA-loaded systems demonstrating significant clinical potential. Challenges such as stability, scalability, and patient adherence are addressed through novel strategies, including Quality by Design (QbD) approaches and advanced imaging tools. This work outlines pathways for future innovation in pulmonary drug delivery.

Keywords: biocompatible carriers; dry powder inhalers; nanoparticle formulations; pulmonary drug delivery; synthetic biomolecules.

Figure 1

Efficient mRNA delivery and innovative dry powder formulations for advanced lung applications [60].

Figure 2

Synergistic INH + D-LAK dry powder formulation with preserved peptide structure, desirable aerosol properties (The section of structures of peptides preserved: Circular dichroism (CD) spectra of SDIA and SDIB formulations containing D-LAK120-A (A) and D-LAK120-HP13 (B). The unformulated peptides were included as controls for comparison) and retained activity against MDR-TB [66].

Figure 3

Overview of DPI Formulation Processing Techniques.

Figure 4

Proliposomal pretomanid DPI: Self-converting liposomal system with enhanced aerosol performance, drug dissolution, and antimycobacterial activity for pulmonary TB treatment [37].