Self-aggregates of 3,6-O,O’-dimyristoylchitosan derivative are effective in enhancing the solubility and intestinal permeability of camptothecin

Abstract

The aim of this work was to investigate the potential of a new 3,6-O,O'-dimyristoyl derivative amphiphilic chitosan (DMCh), in improving the solubility of camptothecin (CPT), a hydrophobic anticancer drug, and its potential oral delivery. FTIR, H NMR and solid-stateC NMR spectroscopy were used to characterize DMCh and to determine its average degree of substitution (DS¯=6.8%). DMCh/CPT micelles size ranged from (281-357nm), zeta potential (+32-50mV) of encapsulation efficiency of 42-100%. The in vitro cell viability showed that DMCh/CPT micelles were able to reduce the toxicity of CPT. The in vitro permeability of CPT through Caco-2 and Caco-2/HT29-MTX intestinal models was increased up to ten fold when formulated into DMCh micelles, underlining the mucoadhesive properties of the nanocarrier. DMCh/CPT micelles are able to enhance CPT solubility and bioavailability while reduce its cytotoxicity, showing the great potential for intestinal delivery of hydrophobic drugs.

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“…The triple co-culture model, Caco-2/HT29-MTX/Raji B, was used for the permeation experiments as it mimics the human intestine better than the Caco-2 model. Indeed, the HT29-MTX cells are mucus-secreting cells and the Raji B cells can induce differentiation of the phenotype Caco-2 into M cells [26].…”

N-(2-Hydroxy)-propyl-3-trimethylammonium, O-Mysristoyl Chitosan Enhances the Solubility and Intestinal Permeability of Anticancer Curcumin

“…It was assumed based on our previous published studies, where similar chitosan micelles were able to retain and protect the drug, providing a hydrophobic drug release less than 20% after 4 h in the gastric and intestinal fluids [49]. The absence of cytotoxicity from the polymers was also expected taking into account our previous work [37,49]. HT29-MTX cell line showed greater sensitivity to the tested samples.…”

“…This means that both micelles systems had the ability to maintain and protect the drug inside of the core, at least during 4 h, showing their potential to be used in the micelles for the release of the drug in the intestine, avoiding the apparent cytotoxicity of CUR. It was assumed based on our previous published studies, where similar chitosan micelles were able to retain and protect the drug, providing a hydrophobic drug release less than 20% after 4 h in the gastric and intestinal fluids [49]. The absence of cytotoxicity from the polymers was also expected taking into account our previous work [37,49].…”

“…In the same sense, taking into account that the CAC value of DMCat was much lower as compared to that of DMCh, the former system was able to form micelles at more dilute solutions, evidencing its higher stability as compared to DMCh [59,60]. DMCat derivative was more stable than the DMCh, a fact that can be explained by the permanent positive charges present in the DMCat, as these charges prevent agglomeration of the micelles by the effect of electrostatic repulsion [37,49].…”

“…Both CUR-loaded DMCh and DMCat micelles were prepared by following the steps described in earlier works [37,48,49]. In essence, DMCh is dissolved in acetic acid 0.1% while DMCat is dissolved in deionized water.…”