Ciprofloxacin-Loaded Inhalable Formulations Against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2024 May 25

PMID 38794310

Authors

Vijay Kumar Panthi

Kathryn E Fairfull-Smith

Nazrul Islam

Affiliations

Soon will be listed here.

Abstract

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives.

Citing Articles

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Wei X, Zhou D, Xu C, Chen P, Chen S, Cheng Z Antibiotics (Basel). 2024; 13(9).

PMID: 39334985 PMC: 11429200. DOI: 10.3390/antibiotics13090810.

Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives.

Panthi V, Fairfull-Smith K, Islam N Pharmaceutics. 2024; 16(5).

PMID: 38794310 PMC: 11125790. DOI: 10.3390/pharmaceutics16050648.

References

Akkerman-Nijland A, Akkerman O, Grasmeijer F, Hagedoorn P, Frijlink H, Rottier B . The pharmacokinetics of antibiotics in cystic fibrosis. Expert Opin Drug Metab Toxicol. 2020; 17(1):53-68. DOI: 10.1080/17425255.2021.1836157. View

Chono S, Tanino T, Seki T, Morimoto K . Efficient drug delivery to alveolar macrophages and lung epithelial lining fluid following pulmonary administration of liposomal ciprofloxacin in rats with pneumonia and estimation of its antibacterial effects. Drug Dev Ind Pharm. 2008; 34(10):1090-6. DOI: 10.1080/03639040801958421. View

Knudsen K, Northeved H, Kumar P, Permin A, Gjetting T, Andresen T . In vivo toxicity of cationic micelles and liposomes. Nanomedicine. 2014; 11(2):467-77. DOI: 10.1016/j.nano.2014.08.004. View

Wilson R, Welte T, Polverino E, Soyza A, Greville H, ODonnell A . Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study. Eur Respir J. 2012; 41(5):1107-15. PMC: 3640146. DOI: 10.1183/09031936.00071312. View

Lin Y, Chang R, Britton W, Morales S, Kutter E, Li J . Inhalable combination powder formulations of phage and ciprofloxacin for P. aeruginosa respiratory infections. Eur J Pharm Biopharm. 2019; 142:543-552. PMC: 6750719. DOI: 10.1016/j.ejpb.2019.08.004. View

Ngan C, Asmawi A . Lipid-based pulmonary delivery system: a review and future considerations of formulation strategies and limitations. Drug Deliv Transl Res. 2018; 8(5):1527-1544. DOI: 10.1007/s13346-018-0550-4. View

Egorov A, Kurliuk A, Rubanik V, Kirichuk A, Khubiev O, Golubev R . Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies. Molecules. 2022; 27(24). PMC: 9784460. DOI: 10.3390/molecules27248865. View

Plaunt A, Nguyen T, Corboz M, Malinin V, Cipolla D . Strategies to Overcome Biological Barriers Associated with Pulmonary Drug Delivery. Pharmaceutics. 2022; 14(2). PMC: 8880668. DOI: 10.3390/pharmaceutics14020302. View

Rubin B . Aerosolized antibiotics for non-cystic fibrosis bronchiectasis. J Aerosol Med Pulm Drug Deliv. 2008; 21(1):71-6. DOI: 10.1089/jamp.2007.0652. View

10.

Shariati A, Arshadi M, Khosrojerdi M, Abedinzadeh M, Ganjalishahi M, Maleki A . The resistance mechanisms of bacteria against ciprofloxacin and new approaches for enhancing the efficacy of this antibiotic. Front Public Health. 2023; 10:1025633. PMC: 9815622. DOI: 10.3389/fpubh.2022.1025633. View

11.

Choi J, Park K, Lee B, Jeong D, Dindulkar S, Choi Y . Solubility and bioavailability enhancement of ciprofloxacin by induced oval-shaped mono-6-deoxy-6-aminoethylamino-β-cyclodextrin. Carbohydr Polym. 2017; 163:118-128. DOI: 10.1016/j.carbpol.2017.01.073. View

12.

Kucukoglu V, Uzuner H, Kenar H, Karadenizli A . In vitro antibacterial activity of ciprofloxacin loaded chitosan microparticles and their effects on human lung epithelial cells. Int J Pharm. 2019; 569:118578. DOI: 10.1016/j.ijpharm.2019.118578. View

13.

Panthi V, Fairfull-Smith K, Islam N . Liposomal drug delivery strategies to eradicate bacterial biofilms: Challenges, recent advances, and future perspectives. Int J Pharm. 2024; 655:124046. DOI: 10.1016/j.ijpharm.2024.124046. View

14.

Gunday Tureli N, Torge A, Juntke J, Schwarz B, Schneider-Daum N, Tureli A . Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections. Eur J Pharm Biopharm. 2017; 117:363-371. DOI: 10.1016/j.ejpb.2017.04.032. View

15.

Chalmers J, Smith M, McHugh B, Doherty C, Govan J, Hill A . Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012; 186(7):657-65. DOI: 10.1164/rccm.201203-0487OC. View

16.

Shi C, Guo K, Zhang L, Guo Y, Feng Y, Cvijic S . In Vitro and In Vivo Evaluation of Inhalable Ciprofloxacin Sustained Release Formulations. Pharmaceutics. 2023; 15(9). PMC: 10537253. DOI: 10.3390/pharmaceutics15092287. View

17.

Wang S, Zhang A, Yao X . Meta-analysis of efficacy and safety of inhaled ciprofloxacin in non-cystic fibrosis bronchiectasis patients. Intern Med J. 2021; 51(9):1505-1512. DOI: 10.1111/imj.15210. View

18.

Shah K, Chan L, Wong T . Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment. Drug Deliv. 2017; 24(1):1631-1647. PMC: 8241194. DOI: 10.1080/10717544.2017.1384298. View

19.

Lin Y, Quan D, Chang R, Chow M, Wang Y, Li M . Synergistic activity of phage PEV20-ciprofloxacin combination powder formulation-A proof-of-principle study in a P. aeruginosa lung infection model. Eur J Pharm Biopharm. 2020; 158:166-171. PMC: 7855557. DOI: 10.1016/j.ejpb.2020.11.019. View

20.

Ong H, Benaouda F, Traini D, Cipolla D, Gonda I, Bebawy M . In vitro and ex vivo methods predict the enhanced lung residence time of liposomal ciprofloxacin formulations for nebulisation. Eur J Pharm Biopharm. 2013; 86(1):83-9. DOI: 10.1016/j.ejpb.2013.06.024. View