title: Development and evaluation of oxaliplatin and irinotecan co-loaded liposomes for enhanced colorectal cancer therapy.
abstract: Drug combinations are widely employed in chemotherapy for colorectal cancer treatment. However, traditional cocktail combination in clinic causes the uncertainty of the treatment, owing to varying pharmacokinetics of different drugs. The aim of this study was to design co-loaded liposomes to achieve the synchronised delivery and release. Oxaliplatin and irinotecan hydrochloride, as one of recommended combination schemes for the treatment of colorectal cancer in clinic, were co-loaded into the liposomes. The particle sizes of the liposomes were <200nm with uniform size distribution. In vitro release study showed that both drugs could be synchronously released from the liposomes, which means the optimized synergistic ratio of two drugs could be achieved. In vitro cellular uptake revealed that co-loaded liposomes could efficiently deliver different drugs into the same cells, indicating their potential as carriers for enhancing the cancer therapy. CLSM images of cryo-sections for in vivo co-delivery study also revealed that co-loaded liposomes had superior ability to co-deliver both the cargoes into the same tumor cells. Besides, in vivo NIRF imaging indicated that the liposomes could increase the drug accumulation in tumor compared with free drug. In vitro cytotoxicity evaluation demonstrated that co-loaded liposomes exhibited higher cytotoxicity than the mixture of single loaded liposomes in both CT-26 and HCT-116 cells. Furthermore, co-loaded liposomes also presented superior anti-tumor activity in CT-26 bearing BALB/c mice. In vivo safety assessment demonstrated that liposomes had lower toxicities than their solution formulations. These results indicated that oxaliplatin and irinotecan hydrochloride co-loaded liposomes would be an efficient formulation for improving colorectal cancer therapy with potential clinical applications.
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
authors.forename: Shaomei
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Song
authors.affiliation: School of Pharmaceutical Science, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China. Electronic address: zhangnancy9@sdu.edu.cn.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Garg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D000077146:Irinotecan; D008081:Liposomes; D008807:Mice, Inbred BALB C; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D000077150:Oxaliplatin; D012007:Rectum / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002166:Camptothecin
keywords: Co-delivery; Co-loaded liposomes; Combination therapy; Irinotecan; Oxaliplatin; Synchronous release