title: Preparation, formula optimization and antitumor actions of mannitol coupling camptothecin nanoparticles.
abstract: The purpose of this work is to prepare a formulation using mannitol coupling Camptothecin (CPT) nanoparticles (CPT-NPs) to circumvent the difficult solubilization practice based on central composite experimental statistical design. CPT-NPs were prepared with a high-pressure homogenization technique method. The independent variables considered for the optimization of CPT-NPs were percentage of CPT in raw material (CPT and mannitol), concentration of CPT in working liquid, cycles numbers and homogenizer pressure for drug loading efficiency, particle size and polydispersity index. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized CPT-NPs showed an appropriate drug loading efficiency (18.09 ± 2.13%), a homogeneous particle size (165.33 ± 37.23 nm) and a low polydispersity index (0.29 ± 0.01). The CPT-NPs group show higher inhibition ratio (79.95%) of H22 tumor growth in vivo compared with TPT and CPT at the same dose. Changes in mice body weight demonstrate CPT-NPs have the lower toxicity. The results of biodistribution studies indicated the obviously superiority of CPT-NPs in increasing the accumulation of CPT within tumor. Overall, CPT-NPs under optimum conditions are considered to be potentially feasible to overcome formulation challenges for drug delivery.
authors: State Engineering Laboratory of Bio-Resources Eco-Utilization, Northeast Forestry University, Ministry of Education, Harbin 150040, China.
authors: Zhichao
authors: Z
authors: Wang
authors: State Engineering Laboratory of Bio-Resources Eco-Utilization, Northeast Forestry University, Ministry of Education, Harbin 150040, China; College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address: li_qingyong@126.com.
authors: Qingyong
authors: Q
authors: Li
authors: State Engineering Laboratory of Bio-Resources Eco-Utilization, Northeast Forestry University, Ministry of Education, Harbin 150040, China.
authors: Xiuhua
authors: X
authors: Zhao
authors: State Engineering Laboratory of Bio-Resources Eco-Utilization, Northeast Forestry University, Ministry of Education, Harbin 150040, China.
authors: Baihe
authors: B
authors: Sun
authors: State Engineering Laboratory of Bio-Resources Eco-Utilization, Northeast Forestry University, Ministry of Education, Harbin 150040, China.
authors: Qiaochu
authors: Q
authors: Zhu
authors: State Engineering Laboratory of Bio-Resources Eco-Utilization, Northeast Forestry University, Ministry of Education, Harbin 150040, China.
authors: Wenqing
authors: W
authors: Gao
authors: State Engineering Laboratory of Bio-Resources Eco-Utilization, Northeast Forestry University, Ministry of Education, Harbin 150040, China.
authors: Changlong
authors: C
authors: Hua
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008353:Mannitol / Q000737:chemistry*; D051379:Mice; D015233:Models, Statistical; D053758:Nanoparticles; D010316:Particle Size; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008353:Mannitol; D002166:Camptothecin
keywords: Antitumor; Camptothecin; Central composite design; High pressure homogenization; Mannitol; Nanoparticles