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Discovery and Basic Research

(T1230-03-16) Formulation and Characterization of Spray-Dried Dermaseptin for Pulmonary Delivery in Lung Cancer Therapy

Tuesday, November 11, 2025
12:30 PM - 1:30 PM CT
Purpose: Lung cancer remains the leading cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Among NSCLC subtypes, lung adenocarcinoma is the most prevalent, often characterized by specific oncogenic mutations that drive disease progression and influence therapeutic response. Although targeted therapies have been developed showing significant outcomes, they often encounter resistance due to secondary mutations and tumor heterogeneity. Therefore, there is a need to develop an alternative which would overcome these resistance mechanisms. Antimicrobial peptides (AMP) like dermaseptin (DSS) prove to be a promising candidate due to its unique mechanism of action via membrane disruption and apoptosis. Dermaseptin is a cationic, amphipathic antimicrobial peptide which is derived from frog skin secretions. Here, we wanted to evaluate the anticancer potential of dermaseptin. Peptide-based therapeutics often suffer from poor stability, enzymatic degradation, and inefficient delivery when administered systemically, we explored pulmonary delivery via inhalable dry powder formulations. This presents a non-invasive, site-specific strategy to directly deliver therapeutics to the lungs, maximizing local concentration while minimizing systemic toxicity. This study aimed to develop a spray-dried dry powder formulation of dermaseptin using specific ratios of different carriers such as trehalose, mannitol, L-leucine and evaluate its physicochemical properties and cytotoxic potential against A549 lung cancer cells. 

Methods: Spray drying was performed using a Büchi B-290 mini-spray dryer with a peptide loading of 5% w/w in a 1% w/v aqueous solution, with fixed ratios of excipients (mannitol:L-leucine:trehalose). The spray drying parameters included a feed rate of 10%, aspirator set to 100%, inlet temperature of 90°C, and outlet temperature of around 42°C. The dry powder yield (% w/w) was calculated by comparing the weight of the collected powder to the total dry mass input. The peptide content in the powder was quantified using high-performance liquid chromatography (HPLC). The spray-dried (DSS-SD) powder was further tested for its physicochemical characterization which included differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA). Additionally, the powder was evaluated for its cytotoxicity properties using A549 lung adenocarcinoma cells by performing the MTT assay, and IC₅₀ values were calculated by nonlinear regression. Further, the aerodynamic properties [mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD)] of the spray-dried powder were tested using the Next Generation ImpactorTM (NGI). 

Results: The spray-dried formulation of dermaseptin (DSS-SD) was successfully prepared with a yield of 56.82 ± 0.25 %w/w, demonstrating a relatively efficient process. The drug loading was determined to be 43.8±5.31 µg of dermaseptin per mg of spray-dried powder. The disappearance of distinct peaks in the XRD diffractogram for the blank spray-dried powder (Blank-SD) and DSS-SD when compared to free peptide (DSS) indicated the uniform dispersion of the peptide within the dry powder (Fig. 1A).  DSC thermograms of the spray-dried formulations (Blank-SD and DSS-SD) demonstrated a single endothermic peak which is a characteristic melting endotherm of mannitol (Fig 1B). Furthermore, TGA was carried out to understand the amount of moisture present in the sample. The spray-dried formulation (DSS-SD) exhibited a low moisture content < 1 %w/w, indicating an efficient drying process (Fig. 1C). A low moisture content is a desirable quality for dry powders for maintaining stability and preventing microbial growth. The in-vitro studies on A549 cells exhibited an IC₅₀ of 11.76 ± 0.74 µM for DSS-SD, which is similar to the IC₅₀ (14.28 ± 1.26 µM) for the free peptide (Fig. 2). These results confirm that the spray drying process did not adversely affect the cytotoxic potential of dermaseptin, making this formulation a promising candidate for inhalable peptide-based therapy targeting lung cancer. Moreover, the aerosolization studies performed using NGI demonstrated most of the particles deposited within stages 3-7. The spray-dried powder exhibited a MMAD of 1.69 µM and a high fine particle fraction (FPF) of greater than 85% w/w, indicating the deposition of the formulation in the respiratory airways (Fig. 3).

Conclusion: In conclusion, dermaseptin was formulated as a spray-dried formulation with desirable physicochemical properties for pulmonary delivery and demonstrated effective anti-cancer activity in NSCLC cells.

Fig. 1. Formulation Characteristics. A. The PXRD diffractogram of DSS, physical mixture, excipients (Mannitol, Trehalose, L-leucine), Blank-SD, and DSS-SD. B. The DSC thermogram of excipients (Mannitol, Trehalose, L-leucine), physical mixture, and Blank-SD. C. The TGA thermogram of DSS-SD.

Fig. 2. Cytotoxicity Assay. Cytotoxicity studies after 48 h treatment with Free drug (DSS), and DSS-SD determined using MTT assay in A549 cell line. Data represents mean ± SD (n = 3)

Fig. 3. Aerosolization performance. In vitro aerosol deposition profile represented as the percentage of drug deposited on each stage of Next Generation ImpactorTM (NGI).