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Fulltext Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis

Alhajj N, Yahya MFZR, O'Reilly NJ, Cathcart H

Eur J Pharm Sci, 2024 Jan 01;192:106654.
PMID: 38013123 DOI: 10.1016/j.ejps.2023.106654

Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED ∼ 71 %; FPF ∼ 49 %) compared to formulations containing MAN and NAC (ED ∼ 64 % and 44 %; FPF ∼ 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.
Fulltext Critical physicochemical attributes of chitosan nanoparticles admixed lactose-PEG 3000 microparticles in pulmonary inhalation

Alhajj N, Zakaria Z, Naharudin I, Ahsan F, Li W, Wong TW

Asian J Pharm Sci, 2020 May;15(3):374-384.
PMID: 32636955 DOI: 10.1016/j.ajps.2019.02.001

Chitosan nanoparticles are exhalation prone and agglomerative to pulmonary inhalation. Blending nanoparticles with lactose microparticles (∼5 µm) could mutually reduce their agglomeration through surface adsorption phenomenon. The chitosan nanoparticles of varying size, size distribution, zeta potential, crystallinity, shape and surface roughness were prepared by spray drying technique as a function of chitosan, surfactant and processing conditions. Lactose-polyethylene glycol 3000 (PEG3000) microparticles were similarly prepared. The chitosan nanoparticles, physically blended with fine lactose-PEG3000 microparticles, exhibited a comparable inhalation performance with the commercial dry powder inhaler products (fine particle fraction between 20% and 30%). Cascade impactor analysis indicated that the aerosolization and inhalation performance of chitosan nanoparticles was promoted by their higher zeta potential and circularity, and larger size attributes of which led to reduced inter-nanoparticulate aggregation and favored nanoparticles interacting with lactose-PEG3000 micropaticles that aided their delivery into deep and peripheral lungs.
Lung cancer: active therapeutic targeting and inhalational nanoproduct design

Alhajj N, Chee CF, Wong TW, Rahman NA, Abu Kasim NH, Colombo P

Expert Opin Drug Deliv, 2018 12;15(12):1223-1247.
PMID: 30422017 DOI: 10.1080/17425247.2018.1547280

INTRODUCTION: Pulmonary drug delivery is organ-specific and benefits local drug action for lung cancer. The use of nanotechnology and targeting ligand enables cellular-specific drug action. Combination approaches increase therapeutic efficacy and reduce adverse effects of cancer chemotherapeutics that have narrow therapeutic index window and high cytotoxicity levels. The current progress of inhaled cancer chemotherapeutics has not been examined with respect to targeting strategy and clinical application potential.
AREAS COVERED: This review examines the state of the art in passive (processing and formulation) and active (targeting ligand and receptor binding) technologies in association with the use of nanocarrier to combat lung cancer. It highlights routes to equip nanocarrier with targeting ligands as a function of the chemistry of participating biomolecules and challenges in inhalational nanoproduct development and clinical applications. Both research and review articles were examined using the Scopus, Elsevier, Web of Science, Chemical Abstracts, Medline, CASREACT, CHEMCATS, and CHEMLIST database with the majority of information retrieved between those of 2000-2018.
EXPERT COMMENTARY: The therapeutic efficacy of targeting ligand-decorated nanocarriers needs to be demonstrated in vivo in the form of finished inhalational products. Their inhalation efficiency and medical responses require further examination. Clinical application of inhaled nanocancer chemotherapeutics is premature.

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