Improved Oral Bioavailability, Therapeutic Efficacy, and Reduced Toxicity of Tamoxifen-Loaded Liquid Crystalline Nanoparticles

被引：24
作者：
Jain, Sanyog [1 ]
Heeralal, B. [1 ]
Swami, Rajan [1 ]
Swarnakar, Nitin K. [1 ]
Kushwah, Varun [1 ]
机构：
[1] NIPER, Sect 67, Dept Pharmaceut, Ctr Pharmaceut Nanotechnol, Sas Nagar Mohali 160062, Punjab, India
来源：
AAPS PHARMSCITECH | 2018年 / 19卷 / 01期
关键词：
tamoxifen; phytantriol; liquid crystalline nanoparticles; oral delivery; breast cancer; P-GLYCOPROTEIN INHIBITION; RATS POSSIBLE ROLE; MAIN METABOLITE; PHARMACOKINETICS; DELIVERY; DRUG; 4-HYDROXYTAMOXIFEN;
D O I：
10.1208/s12249-017-0851-9
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Present investigation deals with formulation and evaluation of tamoxifen (TMX)-loaded liquid crystalline nanoparticles (TMX-LCNPs) for improving oral bioavailability and safety of the existing treatment. Hexagonal Glyceryl monooleate-based TMX-LCNPs (GLCNPs) and Phytantriol-based TMX-LCNPs (PLCNPs) were prepared by dilution-through-hydrotrope method for oral administration. Oleic acid was incorporated in the lipid matrix to enhance the drug loading in the LCNPs. Optimized LCNPs displayed small particle size with a narrow distribution, sustained drug release and high gastrointestinal stability. TMX-LCNPs were found to be considerably higher cytotoxic to MCF-7 cells as compared to free TMX. Substantial fold enhancement in oral bioavailability (similar to 7- and similar to 5-folds with TMX-GLCNPs and TMX-PLCNPs, respectively) was evident followed by significant reduction in tumor burden with lesser hepatotoxicity. Out of the two LCNP formulations, PLCNPs were found to be better in convalescing the disease.
引用
收藏
页码：460 / 469
页数：10
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