Synthesis of 3,6-O,O'-dimyristoylchitosan for encapsulation and release of hydrophobic anticancer drug

Full text: Polymer-based micelles have been frequently proposed for drug encapsulation and release, especially in the case of poorly water soluble drugs. Generally, such micelles present a hydrophilic shell, which prevents its recognition by the immune system, and a hydrophobic core that promotes the drug solubilization and prevents its degradation. However, the development of these systems is still very limited due to the difficulties of preparation and to high costs. To address such limitations, chitosan has been considered as a promising biopolymer due to its biological activities, such as biocompatibility, biodegradability, mucoadhesiveness and antimicrobial activity. In this study, an amphiphilic chitosan derivative, namely 3,6-O,O'-dimyristoylchitosan (DMCh) was produced and applied to encapsulate camptothecin (CPT), a hydrophobic anticancer drug. DMCh was characterized by FTIR, ¹H NMR and solid-state ¹³C NMR spectroscopy, which allowed the determination of its average degree of substitution, DS = 6.8 %. The dynamic light scattering analysis showed that the average size of the micelles DMCh/CPT ranged as 281–357 nm while the zeta potential varied from +32 mV to +50 mV. The encapsulation efficiency was evaluated via UV-Vis spectrophotometry (λ = 370 nm) and it ranged as 42 - 100 %. The in vitro experiments showed that DMCh/CPT micelles were able to reduce significantly the toxicity of CPT and to improve the permeability of CPT through Caco-2 and Caco-2/HT29-MTX intestinal models, highlighting the mucoadhesive properties of such chitosan-based micelles. The DMCh/CPT micelles are able to enhance CPT solubility, showing the great potential for intestinal delivery of hydrophobic drugs. (author)