Co-spray dried inhalable composite powders of ciprofloxacin and alginate oligosaccharide as anti-biofilm therapy

Li Zhang, Hriday Bera, Yi Guo, Changzhi Shi, Johan Ulrik Lind, Carmen Radeke, Junwei Wang, Hengzhuang Wang, Xia Zhao, Dongmei Cun*, Mingshi Yang*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

The treatment of chronic respiratory infections caused by biofilm formation are extremely challenging owing to poor drug penetration into the complex biofilm structure and high drug resistance. Local delivery of an antibiotic together with a non-antibiotic adjuvant to the lungs could often enhance the therapeutic responses by targeting different bacterial growth pathways and minimizing drug resistance. In this study, we designed new inhalable dry powders containing ciprofloxacin (CIP) and OligoG (Oli, a low-molecular-weight alginate oligosaccharide impairing the mucoid biofilms by interacting with their cationic ions) to combat respiratory bacterial biofilm infections. The resulting powders were characterized with respect to their morphology, solid-state property, surface chemistry, moisture sorption behavior, and dissolution rate. The aerosol performance and storage stability of the dry powders were also evaluated. The results showed that inhalable dry powders composed of CIP and Oli could be readily accomplished via the wet milling and spray drying process. Upon the storage under 20 ± 2 °C/20 ± 2 % relative humidity (RH) for one month, there was no significant change in the in vitro aerosol performances of the dry powders. In contrast, the dry powders became non-inhalable following the storage at 20 ± 2 °C/53 ± 2 % RH for one month due to the hygroscopic nature of Oli, which could be largely prevented by incorporation of leucine. Collectively, this study suggests that the newly developed co-spray-dried powders composed of CIP and Oli might represent a promising and alternative treatment strategy against respiratory bacterial biofilm infections.

OriginalsprogEngelsk
Artikelnummer123949
TidsskriftInternational Journal of Pharmaceutics
Vol/bind654
Antal sider12
ISSN0378-5173
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
This research work was financially supported by Liaoning Pan Deng Xue Zhe Scholar (grant no. XLYC2002061), the National Natural Science Foundation of China (grant no. 82173768), and the Overseas Expertise Introduction Project for Discipline Innovation (“111Project”) (grant no. D20029). M.Y. thanks Independent Research Fund Denmark for the financial support (Grant ID: 10.46540/3105-00249B). H.B. thanks the National Natural Science Foundation of China (No. 82050410448) for its financial support.

Publisher Copyright:
© 2024

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