Solubility and bioavailability enhancement of ciprofloxacin by induced oval-shaped mono-6-deoxy-6-aminoethylamino-β-cyclodextrin

• Published in: Carbohydrate polymers 2017-05, Vol.163, p.118-128
• Main Authors: Choi, Jae Min, Park, Kyeonghui, Lee, Benel, Jeong, Daham, Dindulkar, Someshwar D, Choi, Youngjin, Cho, Eunae, Park, Seyeon, Yu, Jae-hyuk, Jung, Seunho
• Format: Article
• Language: English
• Subjects: Ciprofloxacin; Complexation; cyclodextrin; Molecular modeling; Mono-6-deoxy-6-aminoethylamino-β NOESY; Oval-shaped cavity
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2017.01.073

•Mono-6-deoxy-6-aminoethylamino-β-cyclodextrin (Et-β-CD) was synthesized.•Oval-shaped cavity within Et-β-CD was induced by mono aminoethylamine substitution.•Ciprofloxacin (CIP)/Et-β-CD complex was thoroughly characterized.•CIP/Et-β-CD complex effectively enhanced the bioavailability and solubility of CIP. Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic used to treat bacterial infections; however, its limited aqueous solubility inhibits its broader clinical uses. This study investigated the complexation effect of mono-6-deoxy-6-aminoethylamino-β-cyclodextrin on the aqueous solubility and bioavailability of ciprofloxacin. During complexation, the oval-shaped cavity induced by mono-aminoethylamine substitution on the primary rim of β-cyclodextrin, was considered to be a key factor according to NMR spectroscopy and molecular modeling studies. The ciprofloxacin with mono-6-deoxy-6-aminoethylamino-β-cyclodextrin complex was characterized using FE-SEM, DSC, FT-IR, T1 relaxation, 2D NOESY, and DOSY NMR spectroscopy and molecular modeling studies. The solubility property of ciprofloxacin complexed with mono-6-deoxy-6-aminoethylamino-β-cyclodextrin was enhanced by seven-fold compared to that of pure ciprofloxacin. Furthermore antibacterial activity of that complex against methicillin-resistant Staphylococcus aureus was enhanced and it clearly showed the growth inhibition. The mono-6-deoxy-6-aminoethylamino-β-cyclodextrin has the potential to be utilized for other oblong guest molecules besides ciprofloxacin based on the novel induced elliptical cavity.