Development and evaluation of oxaliplatin and irinotecan co-loaded liposomes for enhanced 张娜.pptVIP

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2017-07-03 发布于浙江
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Development and evaluation of oxaliplatin and irinotecan co-loaded liposomes for enhanced 张娜.ppt

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* * Co-loaded liposomes: Oxaliplatin Irinotecan Formulation Design OXA-Lip OXIR-Lip IRI-Lip Single loaded liposomes: Synchronous release Co-delivery * 1. Synergistic effect 2. Preparation and characterization 3. In vitro release 4. In vitro cellular uptake 5. In vitro cytotoxicity 6. In vivo anti-tumor activity 7. Histological analysis Experimental * MTT assay: CT-26 colon cancer cells; Mixture of OXA/IRI; Incubation for 48h; 1. Synergistic effect of oxaliplatin/irinotecan Combination exhibited much lower cell viabilities, indicating strong synergistic potential. * The synergistic effect was calculated via Chou-Talalay Combination Index (CI) method: OXA (μM) IRI (μM) 1:3 (μM) 1:1.5 (μM) 1:1 (μM) 1.5:1 (μM) 3:1 (μM) IC50 (OXA) 65.74±7.25 / 3.88± 1.67 4.27± 0.48 5.33± 1.80 9.34± 1.03 9.68± 3.37 IC50 (IRI) / 63.38± 11.99 11.64± 5.01 6.40± 0.72 5.33± 1.80 6.23± 0.69 3.23± 1.12 CI / / 0.26± 0.15 0.17± 0.05 0.17± 0.08 0.24± 0.06 0.20± 0.10 (CI 1.1, antagonistic; 1.1 CI 0.9, additive; CI 0.9, synergistic) Molar ratio at 1:1.5 or 1:1 had strong synergistic effect, in accordance with the?recommended therapeutic regimen * Preparation method (co-loaded liposomes): Ethanol injection + Ammonium sulfate gradient method Oxaliplatin; (NH4)2SO4 Lipid, Chol Irinotecan Ethanol Injection Oxaliplatin- liposomes Dialysis Co-loaded liposomes 2. Preparation and characterization of the liposomes * Particle size (nm) PDI Zeta potential (mV) EE (%) DL (%) Notes OXA-Lip 184.83 ±2.82 0.090 ±0.015 -3.40 ±0.51 13.81±0.92 2.16±0.14 Ethanol injection IRI-Lip 151.30 ±2.15 0.163 ±0.015 -6.27 ±0.28 91.68±2.35 6.84±0.18 Ammonium sulphate gradient OXIR-Lip 194.63 ±3.97 0.106 ±0.027 -3.03 ±0.13 OXA: 13.44±2.62, IRI: 87.80±6.80 OXA: 2.10±0.40, IRI: 5.09±0.95 Molar ratio of OXA/IRI at 1:1.5 Characterization of different liposomes * Particle size and zeta potential, TEM images of different liposomes OXA-Lip IRI-Lip OXA/IRI-Lip * 3. In vitro drug release In vitro cum