Niclosamide-Colistin Inhalation Powder Research

Multidrug-resistant bacterial infections in the lungs remain one of the most difficult clinical challenges facing people with cystic fibrosis (CF). A newly published study in the International Journal of Pharmaceutics (Romero-Gonzalez et al., 2026) may offer a meaningful step forward — describing a novel particle-engineering approach that combines two antimicrobial agents into a single inhalable dry powder designed to reach the deepest regions of the lung. While the research is still in early-stage development and human clinical data will be needed, the findings highlight a promising formulation strategy for delivering combination antibiotics directly to the site of infection.

What This Study Found

Researchers explored how to co-deliver two antimicrobial compounds — niclosamide and colistin sulfate — via inhalation, specifically targeting multidrug-resistant Gram-negative bacteria that commonly infect the lungs of people with cystic fibrosis. The challenge the team faced was significant: these two compounds have very different physical and chemical properties, making them difficult to formulate together without relying on large amounts of inactive excipients.

To solve this problem, the researchers developed an innovative particle-engineering process called liquid antisolvent precipitation followed by spray drying. In this process, niclosamide — an anthelmintic drug with demonstrated antibacterial synergy — was precipitated into microcrystals from solution, and colistin sulfate was intentionally used not just as a drug, but as a surface-active crystallization stabilizer. This dual-role approach allowed colistin to coat the surface of forming niclosamide crystals, preventing unwanted particle growth and stabilizing the suspension during processing.

The study found that by varying the molar ratio of colistin to niclosamide, researchers could precisely control the resulting particle size of niclosamide — ranging from approximately 7.7 micrometers at a 1:1 ratio down to approximately 1.3 micrometers at a 24:1 ratio. This level of size tunability is critical for inhaled drug delivery, where particle size directly determines how deeply a drug penetrates into the lungs.

The optimized formulation — designated COL-NIC 8:1 — was processed into a dry powder and tested for aerosol performance using a medium-resistance dry powder inhaler. The study reports a fine particle fraction below 5 micrometers of 75.3 ± 1.0%, suggesting a high proportion of the powder would be capable of reaching the lower airways upon inhalation. Solid-state analysis confirmed that niclosamide retained its crystalline structure and showed no evidence of significant chemical interaction with colistin — an important finding for formulation stability and predictable drug behavior.

A preliminary in vivo lung infection model was also used to assess the feasibility of pulmonary delivery and to evaluate the antibacterial response of the co-processed formulation compared to a standard-of-care comparator. The researchers report that the results support the feasibility of this approach, though they emphasize that these findings are early-stage and that further preclinical and clinical investigation will be necessary before this strategy could reach patients.

Clinical Significance

The significance of this research lies in both the drug-resistant pathogen problem it addresses and the elegance of the formulation solution it proposes. Cystic fibrosis patients are disproportionately affected by chronic lung infections caused by Gram-negative bacteria such as Pseudomonas aeruginosa and Burkholderia cepacia complex — organisms that are increasingly resistant to conventional antibiotic therapies. Colistin is often considered a last-resort antibiotic for these infections, but resistance to colistin itself is a growing concern.

The in vitro synergy between niclosamide and colistin against multidrug-resistant pathogens, reported as the basis for this study, suggests that combining these agents may help lower the effective doses required for each drug while improving bactericidal outcomes. By delivering them directly to the lungs through inhalation rather than systemically, the approach may also reduce systemic toxicity — a known concern with colistin when administered intravenously.

Perhaps most noteworthy from a pharmaceutical science perspective is the concept of using one active drug as a processing aid for another. This excipient-minimized strategy avoids the need for inactive stabilizers that add formulation complexity, regulatory burden, and potential tolerability issues in compromised lungs. The study suggests this platform could potentially be adapted for other difficult-to-combine drug pairs in respiratory medicine, though this remains speculative at this stage.

It is important to note that the in vivo data reported in this study comes from an animal lung infection model, not from human clinical trials. As the authors acknowledge, these results establish feasibility and proof-of-concept — human studies will be essential to determine safety, tolerability, effective dosing, and clinical outcomes in CF patients.

Current Access and Compliance Context

Inhaled antibiotic therapy is already an established part of CF care — inhaled tobramycin and aztreonam lysine are approved and widely used. However, for infections caused by organisms resistant to these agents, treatment options narrow considerably. Colistin is available in inhaled form in some countries for compassionate or off-label use, but standardized, optimized inhalable colistin formulations with combination partners remain an unmet need.

Dry powder inhalers (DPIs), the delivery platform used in this study, are generally preferred in CF management for their portability, lack of nebulization time, and reduced contamination risk compared to liquid nebulizers. A high-drug-loading DPI formulation that requires no additional excipients could also simplify manufacturing and potentially reduce the treatment burden for patients already managing complex daily medication regimens.

Currently, no niclosamide-colistin combination inhalation product is approved or commercially available. The research described here is at the preclinical formulation stage, and a significant pathway — including toxicology studies, clinical trials, and regulatory review — would be required before any such product could become available to patients.

What Patients Should Know

If you or a loved one is living with cystic fibrosis and managing chronic or recurrent lung infections, it is understandable to follow emerging research with interest. Here is what is important to understand about this study:

This research is promising but early. The findings come from laboratory and animal model experiments. The study has not yet been tested in human clinical trials, and there is no guarantee that results observed in animal models will translate to humans.

Niclosamide is not currently approved for lung infections. Niclosamide is an antiparasitic drug with a long safety history, but its use as an inhaled antibacterial agent is investigational. Do not attempt to obtain or use niclosamide or colistin outside of physician supervision.

Speak with a CF specialist. If you have questions about current treatment options for drug-resistant infections, or about participation in clinical research, your pulmonologist or CF care team is the best resource. Emerging therapies like this one must go through rigorous evaluation before they become standard of care.

Stay informed through reputable sources. Organizations such as the Cystic Fibrosis Foundation track ongoing research and clinical trials that may be relevant to your care.

Conclusion

The study by Romero-Gonzalez and colleagues represents an innovative step in the pharmaceutical engineering of inhaled antibiotic combinations for cystic fibrosis-related lung infections. By leveraging colistin sulfate simultaneously as a therapeutic agent and a crystallization stabilizer, researchers developed an excipient-minimized dry powder formulation of niclosamide and colistin with favorable aerosol properties and promising early antibacterial activity in a preclinical model. While human clinical data will be essential to validate these findings, the platform described could have meaningful implications for how combination inhaled antibiotics are designed and delivered in the future.

To connect with a qualified healthcare provider who stays current with emerging research in respiratory medicine and antimicrobial therapy, visit peptideassociation.org/find-a-doctor.

Medical Disclaimer: This article is intended for educational and informational purposes only and does not constitute medical advice. The content summarizes published scientific research and should not be used as a basis for self-diagnosis or self-treatment. Always consult a licensed healthcare professional before making any decisions regarding your health, medications, or treatment plans. The Peptide Association does not endorse any specific therapy, drug, or clinical product.

Citation (AMA Format): Romero-Gonzalez M, Park M, Chen Z, et al. Colistin-stabilized antisolvent precipitation enables engineering of microcrystalline niclosamide for inhalable composite powders. Int J Pharm. 2026;(April). doi:10.1016/j.ijpharm.2026.126791. PMID: 41864446.