TY - JOUR

T1 - Co-spray dried inhalable composite powders of ciprofloxacin and alginate oligosaccharide as anti-biofilm therapy

AU - Zhang, Li

AU - Bera, Hriday

AU - Guo, Yi

AU - Shi, Changzhi

AU - Ulrik Lind, Johan

AU - Radeke, Carmen

AU - Wang, Junwei

AU - Wang, Hengzhuang

AU - Zhao, Xia

AU - Cun, Dongmei

AU - Yang, Mingshi

N1 - Publisher Copyright: © 2024

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Aerosol performances

KW - Inhaled dry powders

KW - Nanocrystals

KW - Spray drying

KW - Storage stability

U2 - 10.1016/j.ijpharm.2024.123949

DO - 10.1016/j.ijpharm.2024.123949

M3 - Journal article

C2 - 38417723

AN - SCOPUS:85187575827

VL - 654

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 123949

ER -