Pulmonary delivery of spray-dried Nisin ZP antimicrobial peptide for non-small cell lung cancer (NSCLC) treatment

[Display omitted] Nisin ZP is an antimicrobial peptide (AMP) produced by the bacterium Lactococcus lactis, and we have previously demonstrated anticancer activity in NSCLC (A549) cells. In this study, we formulated a nisin ZP dry powder (NZSD) using a spray dryer to facilitate inhaled delivery for t...

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Published in:International journal of pharmaceutics 2023-03, Vol.634, p.122641-122641, Article 122641
Main Authors: Patil, Suyash M., Barji, Druva Sarika, Aziz, Sophia, McChesney, David A., Bagde, Shapali, Muttil, Pavan, Kunda, Nitesh K.
Format: Article
Language:English
Subjects:
Administration, Inhalation
Antimicrobial Peptides
Antimicrobial Peptides (AMPs)
Carcinoma, Non-Small-Cell Lung
Dry powder
Dry Powder Inhalers
Humans
Lung
Lung Neoplasms
Nisin
Nisin ZP
Non-small Cell Lung Cancer (NSCLC)
Particle Size
Powders - chemistry
Pulmonary delivery
Respiratory Aerosols and Droplets
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Summary:[Display omitted] Nisin ZP is an antimicrobial peptide (AMP) produced by the bacterium Lactococcus lactis, and we have previously demonstrated anticancer activity in NSCLC (A549) cells. In this study, we formulated a nisin ZP dry powder (NZSD) using a spray dryer to facilitate inhaled delivery for the treatment of NSCLC. Nisin ZP was spray-dried with mannitol, l-leucine, and trehalose in a ratio of 75:15:10 using Büchi mini spray-dryer B-290 in different drug loadings (10, 20, and 30% w/w). NZSD powder revealed a good powder yield of >55% w/w with ≤3 % w/w moisture content and high nisin ZP drug loading for all the peptide ratios. The NZSD powder particles were irregularly shaped with corrugated morphology. The presence of an endothermic peak in DSC thermograms and attenuated crystalline peaks in PXRD diffractograms confirmed the semi-crystalline powder nature of NZSD. The anticancer activity of nisin ZP was maintained after fabricating it into NZSD powder and showed a similar inhibitory concentration to free nisin ZP. Stability studies indicated that NZSD powders were stable for three months at 4 and 25 ℃ with more than 90% drug content and semi-crystalline nature, as confirmed by DSC and PXRD. Aerosolization studies performed using NGI indicated an aerodynamic diameter (MMAD) within the desired range (1–5 µm) and a high fine particle fraction (FPF > 75%) for all peptide ratios, suggesting powder deposition in the lung's respiratory airways. In conclusion, a dry powder of nisin ZP was formulated using a spray dryer with enhanced storage stability and suitable for inhaled delivery.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2023.122641