Methyl-β-cyclodextrin quaternary ammonium chitosan conjugate: nanoparticles vs macromolecular soluble complex

Purpose: The present study aimed to compare a novel cyclodextrin–polymer–drug complex in solution with a dispersed supramolecular nanosize system, made of the same complex, for ability to carry dexamethasone (DEX) across excised rat intestine. Results: Methyl-β-cyclodextrin-quaternary ammonium chitosan conjugate (QA-Ch-MCD) was obtained by covalent grafting through a 10-atom spacer. The conjugate was characterized by 1H-NMR, resulting in 24.4% w/w of MCD content. Phase solubility profile analysis of the QA-Ch-MCD/DEX complex yielded an association constant of 14037 M-1, vs 4428 M-1 for the plain MCD/DEX complex. Nanoparticle (NP) dispersions resulted from ionotropic gelation of the QA-Ch-MCD/DEX complex by sodium tripolyphosphate, leading to 9.9%±1.4% drug loading efficiency. The mean diameter and zeta potential for NP were 299±32 nm (polydispersity index [PI] 0.049) and 11.5±1.1 mV, respectively. Those for QA-Ch-MCD/DEX were 2.7±0.4 nm (PI 0.048) and 6.7±0.6 mV. QA-Ch-MCD/DEX solutions and corresponding NP dispersions were compared in vitro for water-assisted transport through mucus, DEX permeation through excised rat intestine, and ex vivo mucoadhesivity. The complex showed higher mucoadhesion and lower transport rate through mucus; also, it provided faster drug permeation across excised rat intestine. Conclusion: Carrier adhesion to mucus surface has played a most important role in favoring transepithelial permeation. Then, within the concerns of the present study, the use of NP seems not to provide any determinant advantage over using the simpler macromolecular complex. © 2018 Piras et al.