Résumé
To improve the solubility of quercetin ( QT) , one of flavonoids that can inhibit the proliferation of vari-ous types of cancer cells, the novel amphiphilic polymer N-( 4-methylimidazole)-hydroxyethyl-chitosan ( MHC) , synthetized by chemical derivatization from chitosan, was used as the self-assembly micelles of QT. The formed polymer was characterized by 1 H NMR, elemental analysis and pyrene fluorescence spectrometry. The formulation of MHC micelles loading quercetin was optimized through single factor experiment. Then the optimized formulation was obtained as follows:the concentration of MHC was 0. 67% and the ratio of drug and carrier was 1 ∶10. The micelles particle size was ( 99. 21 ± 1. 71) nm, Zeta potential was +( 20. 01 ± 0. 72) mV and drug loading was ( 5. 42 ± 0. 32 )%. The in vitro release curve was investigated and was found to conform to Higuchi equation of Q=0. 1101 t1/2 -0. 064. The results of in vivo experiment showed that the mean rentention time and bioavail-ability of the MHC-QT micelles were 21. 42 h and 57. 49 μg h/mL, respectively, compared to 0. 30 h and 2. 50 μg h/mL of the free QT solution. These indicated that the MHC micelles could significantly improve the solubility of QT, the drug sustained-release effect and bioavailability, which would used as carrier for the anti-tumor drugs.
Résumé
OBJECTIVE:To study the percutaneous properties of Man-PEI25k nanocomplex under the treatment of microneedles. METHODS:Using fluorescent dye water-soluble carboxyl CdSe/ZnS quantum dot (QD) as model drug, Man-PEI25k/QD and Man-PEI25k/QD nanocomplex with different grafting rates(1∶3,1∶6)were formed through electrostatic adherence with PEI25k and Man-PEI25k. The distribution of QD in the active epidermal layer and dermis of skin were observed by confocal microscopy after the treatment of microneedles,using free QD as control. The accumulative retention amounts of QD in the active epidermal layer and dermis of skin were determined by fluorescence spectrophotometer after PEI25k/QD and Man-PEI25k/QD nanocomplex treated with mi-croneedles. RESULTS:The amounts of Man-PEI25k/QD nanocomplex in active epidermal layer and dermis were significantly higher than that of PEI25k/QD nanocomplex under the treatment of microneedles in vivo;the amounts of Man-PEI25k/QD (1∶6) nanocom-plex in active epidermal layer and dermis of skin were significantly higher than that of Man-PEI25k/QD(1∶3)nanocomplex. In in vi-tro transdermal diffusion experiments,microneedles could increase the retention amounts of nanocomplex in active epidermal layer and dermis of skin significantly. The retention amounts of Man-PEI25k/QD nanocomplex in active epidermal layer were increased by 2 times of that of PEI25k/QD under the treatment of microneedles after 48 h;at the same time,in the dermis that was increased by 1.5 times,with statistical significance (P<0.01). CONCLUSIONS:Microneedles can improve the percutaneous properties of Man-PEI25k nanocomplex in active epidermal layer.