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Volume 18
Issue 4
10.3390/pharmaceutics18040428
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Article

pH-Responsive Nanostructured Calcium Phosphate Microrods as Pulmonary Delivery Platform: Fabrication, Characterization, and Comparative Assessment of Cytotoxic and Transcriptomic Responses in Alveolar Macrophages

by
Jannis Fries
1,2,
Richard Bachmann
2,3,
Amalia Schechtel
1,2,
Oliver Janka
4,
Julia Schulze-Hentrich
2,3 and
Marc Schneider
1,2,*
1
Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, Campus C4 1, 66123 Saarbrücken, Germany
2
PharmaScienceHub (PSH), 66123 Saarbrücken, Germany
3
Department of Genetics and Epigenetics, Saarland University, Campus A2 4, 66123 Saarbrücken, Germany
4
Department of Chemistry, Inorganic Solid-State Chemistry, Saarland University, Campus C4 1, 66123 Saarbrücken, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2026, 18(4), 428; https://doi.org/10.3390/pharmaceutics18040428
Submission received: 13 February 2026 / Revised: 20 March 2026 / Accepted: 28 March 2026 / Published: 31 March 2026
(This article belongs to the Topic Advanced Nanotechnology in Drug Delivery Systems)
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Abstract

Background: Nanostructured, rod-shaped microparticles represent a promising drug delivery platform for the pulmonary delivery and targeting of alveolar macrophages by exploiting the aerodynamic advantages of fiber-like geometries. These microrods feature a hierarchical architecture, designed for potential macromolecular payloads, and silica (SiO2)-based systems have previously been shown to successfully deliver oligonucleotides in vitro. However, current microrod systems mainly rely on nanoparticulate SiO2-based frameworks with limited biodegradability and lack a specific escape mechanism to the cytosol. Therefore, a nanostructured calcium phosphate (CaP) framework is proposed as a biodegradable and resorbable alternative, featuring pH-responsive dissolution under endolysosomal conditions. Methods and Results: This study presents the fabrication of nanostructured, rod-shaped calcium phosphate microparticles and discusses their suitability as a potential pulmonary drug delivery platform. The particles feature dissolution-driven disintegration in acidic and ion-rich environments relevant to phagolysosomes. In addition, the particles exhibited a favorable acute cytotoxicity profile in the murine alveolar macrophage cell line MH-S compared with their SiO2-based counterparts. Comparative RNA-seq analysis of MH-S exposed to the particles indicates a mild transcriptomic response, while canonical signatures of classical or alternative macrophage activation programs were not observed, supporting a generally well-tolerated exposure profile of the carrier. Conclusions: Together, these findings establish key prerequisites for employing calcium phosphate microrods as a biodegradable pulmonary carrier platform in subsequent studies incorporating therapeutic cargos.
Keywords: microcylinders; calcium phosphate; aerodynamic properties; smart delivery; cell interaction; RNA-seq; alveolar mouse macrophages; pH responsiveness microcylinders; calcium phosphate; aerodynamic properties; smart delivery; cell interaction; RNA-seq; alveolar mouse macrophages; pH responsiveness
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MDPI and ACS Style

Fries, J.; Bachmann, R.; Schechtel, A.; Janka, O.; Schulze-Hentrich, J.; Schneider, M. pH-Responsive Nanostructured Calcium Phosphate Microrods as Pulmonary Delivery Platform: Fabrication, Characterization, and Comparative Assessment of Cytotoxic and Transcriptomic Responses in Alveolar Macrophages. Pharmaceutics 2026, 18, 428. https://doi.org/10.3390/pharmaceutics18040428

AMA Style

Fries J, Bachmann R, Schechtel A, Janka O, Schulze-Hentrich J, Schneider M. pH-Responsive Nanostructured Calcium Phosphate Microrods as Pulmonary Delivery Platform: Fabrication, Characterization, and Comparative Assessment of Cytotoxic and Transcriptomic Responses in Alveolar Macrophages. Pharmaceutics. 2026; 18(4):428. https://doi.org/10.3390/pharmaceutics18040428

Chicago/Turabian Style

Fries, Jannis, Richard Bachmann, Amalia Schechtel, Oliver Janka, Julia Schulze-Hentrich, and Marc Schneider. 2026. "pH-Responsive Nanostructured Calcium Phosphate Microrods as Pulmonary Delivery Platform: Fabrication, Characterization, and Comparative Assessment of Cytotoxic and Transcriptomic Responses in Alveolar Macrophages" Pharmaceutics 18, no. 4: 428. https://doi.org/10.3390/pharmaceutics18040428

APA Style

Fries, J., Bachmann, R., Schechtel, A., Janka, O., Schulze-Hentrich, J., & Schneider, M. (2026). pH-Responsive Nanostructured Calcium Phosphate Microrods as Pulmonary Delivery Platform: Fabrication, Characterization, and Comparative Assessment of Cytotoxic and Transcriptomic Responses in Alveolar Macrophages. Pharmaceutics, 18(4), 428. https://doi.org/10.3390/pharmaceutics18040428

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