# Advantages of the Combined Use of Cyclodextrins and Chitosan in Drug Delivery: A Review

## TL;DR

This review discusses how combining cyclodextrins and chitosan can improve drug delivery by overcoming their individual limitations.

## Contribution

The paper provides a comprehensive review of the combined use of cyclodextrins and chitosan in drug delivery over the past 25 years.

## Key findings

- Cyclodextrins improve drug solubility and stability but face issues with rapid removal and competition in vivo.
- Chitosan offers mucoadhesive and controlled release properties but struggles with solubility and affinity for hydrophobic drugs.
- Combining cyclodextrins and chitosan can enhance drug delivery by leveraging their complementary properties.

## Abstract

Cyclodextrins and chitosan are biomaterials largely used as pharmaceutical excipients due to their biocompatibility, biodegradability, and low/absent toxicity, associated with a number of favorable properties. In particular, cyclodextrins complexation is mainly utilized to improve the physicochemical and biological properties of drugs, including solubility, stability, and bioavailability, and to reduce their irritating effect. Nevertheless, some disadvantages related to the fast removal of the complex from blood circulation after in vivo administration, and possible competition effects for interaction with cyclodextrin between the complexed drug and other molecules present in the biological environment, can reduce their efficacy as drug carriers. On the other hand, chitosan is widely employed to take advantage of its mucoadhesive, controlled/targeted release, and permeation-enhancing properties. However, its almost complete insolubility in water and poor affinity towards hydrophobic molecules (as most drugs are) are considered its main drawbacks, which could strongly limit its applicability. Due to the several beneficial properties of both cyclodextrins and chitosan, their joint use could provide additional favorable effects in drug delivery and help overcome their disadvantages, in particular by combining the complexing/solubilizing ability of the former towards hydrophobic molecules with the mucoadhesive and controlled/targeted release properties of the latter. The present review is intended to provide a critical and comprehensive summary of the main relevant investigations performed in the last twenty-five years regarding the applications and possible advantages that can be obtained by the combined use of cyclodextrins and chitosan in the development of more effective drug delivery systems.