Effect of cross-linking on the inclusion complex formation of derivatized β-cyclodextrins with small-molecule drug moxifloxacin

• Published in: Carbohydrate research Vol. 498; p. 108183
• Main Authors: Skuredina, Anna A., Le-Deygen, Irina M., Belogurova, Natalya G., Kudryashova, Elena V.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.12.2020
• Subjects: Antibacterial; Cross-linking; FTIR spectroscopy; Moxifloxacin; Nanoparticle; Substituted β-cyclodextrin; Substituted β-cyclodextrin; Moxifloxacin; Antibacterial; Cross-linking; Nanoparticle; FTIR spectroscopy
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2020.108183

Derivatized β-cyclodextrins (CDs), cyclic oligomers of glucose with inner cavity, are able to form the inclusion complex with many poorly soluble lipophilic organic molecules, including drugs, thus improving their solubility in aqueous solutions and drug bioavailability. Here, we have studied the effect of cross-linking of derivatized CDs with different substituent nature, on their binding with antibacterial drug moxifloxacin (MF) which served as a model small molecule drug. Cross-linking of derivatized CDs with 1,6-hexamethylene diisocyanate (HMD) yielded 100–200 nm nanoparticles with distinct binding properties, strongly depending on the nature of the CD substituent, degree of oligomerization, and the nanoparticle's charge. Interestingly, substituent that improved MF binding to monomeric CDs the most (methyl moiety), had reverse effect in the case of cross-linked CD. Whereas the substituent that had only limited effect on the monomeric CD (sulfobutyl ether moiety), improved binding of cross-linked CD by almost two orders of magnitude. Further, we show that the cross-linked CD complexes with MF perform better in vitro antibacterial assay on E.coli, compared to both free MF and monomeric CD-MF. Overall, this data indicates the potential utility of CD cross-linking and derivatization to develop small molecule drug formulations with improved pharmacological properties. [Display omitted] •Cross-linking of derivatized β-cyclodextrins has dramatic effects on the inclusion complex formation with moxifloxacin.•Mechanisms, stabilizing the complex, may be different for cross-linked vs monomeric CD derivatives.•Nanoparticles with negative ζ-potential possess higher affinity for moxifloxacin compared to monomeric β-CD derivatives.•Complex formation enables prolonged drug release and higher antibacterial activity in vitro assay.