Polysaccharide Submicrocarrier for Improved Pulmonary Delivery of Poorly Soluble Anti-infective Ciprofloxacin: Preparation, Characterization, and Influence of Size on Cellular UptakeClick to copy article linkArticle link copied!
- Duy-Khiet HoDuy-Khiet HoHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbrücken, GermanyDepartment of Pharmacy, Saarland University, D-66123 Saarbrücken, GermanyMore by Duy-Khiet Ho
- Ana CostaAna CostaI3S, Instituto de Investigação e Inovação em Saúde Universidade do Porto, 4200-135 Porto, PortugalInstituto Nacional de Engenharia Biomédica (INEB), Universidade do Porto, 4200-135 Porto, PortugalInstituto Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, PortugalMore by Ana Costa
- Chiara De RossiChiara De RossiHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbrücken, GermanyMore by Chiara De Rossi
- Cristiane de Souza Carvalho-WodarzCristiane de Souza Carvalho-WodarzHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbrücken, Germany
- Brigitta Loretz*Brigitta Loretz*E-mail: [email protected]Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbrücken, GermanyMore by Brigitta Loretz
- Claus-Michael LehrClaus-Michael LehrHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, D-66123 Saarbrücken, GermanyDepartment of Pharmacy, Saarland University, D-66123 Saarbrücken, GermanyMore by Claus-Michael Lehr
Abstract
The majority of the currently used and developed anti-infectives are poorly water-soluble molecules. The poor solubility might lead to limited bioavailability and pharmacological action of the drug. Novel pharmaceutical materials have thus been designed to solve those problems and improve drug delivery. In this study, we propose a facile method to produce submicrocarriers (sMCs) by electrostatic gelation of anionic ß-cyclodextrin (aß-CD) and chitosan. The average hydrodynamic size ranged from 400 to 900 nm by carefully adjusting polymer concentrations and N/C ratio. The distinct host–guest reaction of cyclodextrin derivative is considered as a good approach to enhance solubility, and prevent drug recrystallization, and thus was used to develop sMC to improve the controlled release profile of a poorly soluble and clinically relevant anti-infective ciprofloxacin. The optimal molar ratio of ciprofloxacin to aß-CD was found to be 1:1, which helped maximize encapsulation efficiency (∼90%) and loading capacity (∼9%) of ciprofloxacin loaded sMCs. Furthermore, to recommend the future application of the developed sMCs, the dependence of cell uptake on sMCs size (500, 700, and 900 nm) was investigated in vitro on dTHP-1 by both flow cytometry and confocal microscopy. The results demonstrate that, regardless of their size, an only comparatively small fraction of the sMCs were taken up by the macrophage-like cells, while most of the carriers were merely adsorbed to the cell surface after 2 h incubation. After continuing the incubation to reach 24 h, the majority of the sMCs were found intracellularly. However, the sMCs had been designed to release sufficient amount of drug within 24 h, and the subsequent phagocytosis of the carrier may be considered as an efficient pathway for its safe degradation and elimination. In summary, the developed sMC is a suitable system with promising perspectives recommended for pulmonary extracellular infection therapeutics.
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