Synthesis and characterization of low-toxicity N-caprinoyl-N-trimethyl chitosan as self-assembled micelles carriers for osthole

Abstract

Novel amphiphilic chitosan derivatives (N-caprinoyl-N-trimethyl chitosan [CA-TMC]) were synthesized by grafting the hydrophobic moiety caprinoyl (CA) and hydrophilic moiety trimethyl chitosan to prepare carriers with good compatibility for poorly soluble drugs. Based on self-assembly, CA-TMC can form micelles with sizes ranging from 136 nm to 212 nm. The critical aggregation concentration increased from 0.6 mg ⋅ L −1 to 88 mg ⋅ L −1 with decrease in the degree of CA substitution. Osthole (OST) could be easily encapsulated into the CA-TMC micelles. The highest entrapment efficiency and drug loading of OST-loaded CA-TMC micelles(OST/CA-TMC) were 79.1% and 19.1%, respectively. The antitumor efficacy results show that OST/CA-TMC micelles have significant antitumor activity on Hela and MCF-7 cells, with a 50% of cell growth inhibition (IC50) of 35.8 and 46.7 µg ⋅ mL −1 , respectively. Cell apoptosis was the main effect on cell death of Hela and MCF-7 cells after OST administration. The blank micelles did not affect apoptosis or cell death of Hela and MCF-7 cells. The fluorescence imaging results indicated that OST/CA-TMC micelles could be easily uptaken by Hela and MCF-7 cells and could localize in the cell nuclei. These findings suggest that CA-TMC micelles are promising carriers for OST delivery in cancer therapy.

Modification of Chitosan for the Generation of Functional Derivatives

“…As another example, TMC micelles can be prepared to overcome subasorption and solulibitly problems of specific active molecules, such as insoluble alkaloid, osthole, etc. [185,186]. The use of nanoparticles is not new and current papers deal with specific derivatives such as carboxymethyl CS (CMCS), which are soluble Very recently, Mittal et al [174] published a deep and comprehensive review that scientist readers should adress to fully understand the progress of CS chemistry for use in biomedical fields, as well as the paper of Laroche et al [4], which highlighted the need for an integral approach to comprehend all the potential of CS and its derivatives.…”

“…As another example, TMC micelles can be prepared to overcome subasorption and solulibitly problems of specific active molecules, such as insoluble alkaloid, osthole, etc. [185,186]. The use of nanoparticles is not new and current papers deal with specific derivatives such as carboxymethyl CS (CMCS), which are soluble in both acidic and alkaline solutions, for designing nanotechnology-bases systems based on stimulus-based, diffusion, swelling, or erosion-controlled release [187].…”

Immunoisolation of stem cells by simultaneous encapsulation and PEGylation

“…FTIR spectra of C–O–C bond at 1030 cm −1 for alginate, alginate–TMC, and alginate–TMC–PEG microcapsules are related to alginate (Coates 2000 ; Hu et al 2013 ). The observed peak at 1441 cm −1 in alginate–TMC spectrum is related to N–CH 3 bond of amino group that indicates the presence of TMC layer.…”

Antibacterial Polyelectrolytic chitosan derivatives conjugated natural rubber latex films with minimized bacterial adhesion

“…Two new peaks corresponding to C-H bending vibrations at 1506 cm −1 and 1,466 cm −1 depict successful quaternization. [38,39]…”