A liver-targeting preparation of hydroxycamptothecin using lipid-encapsulated mesoporous silica as a carrier and its preparation method
A technology of mesoporous silica and hydroxycamptothecin, which is applied in the field of new dosage forms of tumor drugs in pharmacy, and can solve the problems of low drug loading, no specific targeting, and instability
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Embodiment 1
[0024] Preparation and Characterization of Hydroxycamptothecin Liver Targeting Preparation Using Lipid-encapsulated Mesoporous Silica as Carrier
[0025] S1. Using the improved Preparation of mesoporous silica by method: Dissolve 0.0061mol / L cetyltrimethylammonium bromide, 0.0118mol / L NaOH solution and absolute ethanol (alcohol-water ratio=1:8, v / v) in 120mL Stir in deionized water for 20min at 80°C, then slowly add 0.0512mol / L tetraethyl orthosilicate dropwise, continue stirring for 2h, centrifuge the reaction solution at 16,000rpm, and wash the precipitate with water and alcohol for 3 times , vacuum-dried overnight; the resulting powder was added to a 5.3% hydrochloric acid / absolute ethanol mixture at a ratio of 1g:100mL, refluxed and extracted at 80°C for 6h, the reaction solution was centrifuged at 16,000rpm, and the obtained precipitate was washed with water and alcohol After 3 times each, vacuum-dry overnight to obtain monodisperse spherical mesoporous silica (MSN);
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Embodiment 2
[0034] In vitro drug release behavior of hydroxycamptothecin liver-targeted preparations supported by lipid-encapsulated mesoporous silica
[0035] Precisely measure 2mL of HCPT-GC-LMSN suspension in a dialysis bag, tie the two ends tightly with a thin cotton rope to ensure that the solution in the bag does not leak, put it in phosphate buffer solution containing 1% SDS, and keep at a certain temperature Shake at 100±1rpm for 36h. At 0, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h and 36h, draw 5mL of release medium, and supplement the same volume of release medium at the same time. After the sample was filtered through a 0.45 μm filter membrane, the release amount of hydroxycamptothecin in the release medium was measured by high performance liquid chromatography, and the cumulative release rate was calculated. In the same way, an equivalent amount of hydroxycamptothecin crude drug was taken as a control.
[0036] Release medium: phosphate buffer containing 1% SDS pH=5.8, phos...
Embodiment 3
[0039] Cell Viability Assay of a Liver-Targeted Preparation of Hydroxycamptothecin Using Lipid-Encapsulated Mesoporous Silica
[0040] HepG 2 The cells were cultured in DMEM high-glucose medium containing 10% fetal bovine serum, and were divided into HCPT group and HCPT-GC-LMSN group, each divided into 1×10 4 The cell density of each was seeded in a 96-well plate, and after 24 hours of adherent culture, the concentration of hydroxycamptothecin was administered at 2.5 μg / mL, 5 μg / mL, 10 μg / mL, 20 μg / mL and 40 μg / mL, respectively. Then continue to culture for 24h, 48h, 72h. After each culture stage, 10 μL of CCK-8 was added to each well, incubated at 37°C for 1 h, the OD value was detected with a microplate reader, and the cell viability was calculated. median lethal dose (IC 50 ) were calculated using SPSS software.
[0041] Depend on Figure 9 It can be seen that when different concentrations of HCPT act on HepG 2 After cells, both the HCPT group and the HCPT-GC-LMSN gro...
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