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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Biomaterials

Background:

• Cyclodextrin-polymer conjugates offer potential for drug complexation and delivery.
• Supramolecular nanosystems can enhance drug transport, but their advantages need evaluation.
• Dexamethasone (DEX) delivery across intestinal barriers remains a challenge.

Purpose of the Study:

• To compare a novel cyclodextrin-polymer-drug complex with a nanosize system for dexamethasone (DEX) intestinal transport.
• To evaluate the role of mucoadhesion in enhancing drug permeation across excised rat intestine.

Main Methods:

• Synthesis and characterization of a methyl-β-cyclodextrin-quaternary ammonium chitosan conjugate (QA-Ch-MCD).
• Formation of QA-Ch-MCD/DEX complex and its subsequent nanoparticle (NP) dispersion via ionotropic gelation.
• In vitro assessment of mucoadhesivity, mucus transport, and DEX permeation through excised rat intestine.

Main Results:

• The QA-Ch-MCD/DEX complex exhibited a significantly higher association constant (14037 M⁻¹) than plain MCD/DEX (4428 M⁻¹).
• Nanoparticles (NP) of QA-Ch-MCD/DEX measured 299±32 nm, while the complex itself formed smaller structures (2.7±0.4 nm).
• The QA-Ch-MCD/DEX complex showed enhanced mucoadhesion, reduced mucus transport, and faster DEX permeation across rat intestine compared to NP.

Conclusions:

• Carrier mucoadhesion to the intestinal mucus surface is crucial for improving transepithelial drug permeation.
• The simpler macromolecular QA-Ch-MCD/DEX complex provided comparable or superior intestinal drug delivery compared to its nanoparticle form.
• Nanosystems did not offer a significant advantage over the macromolecular complex for DEX intestinal transport in this study.