Oleanolic–bioenhancer coloaded chitosan modified nanocarriers attenuate breast cancer cells by multimode mechanism and preserve female fertility
| Autor: | Komal Sharma, Anil Kumar Dwivedi, Santosh Kumar Yadav, Monika Sharma, Sarvesh Paliwal, Shweta Sharma, Ajay Kumar Singh Rawat, Pankaj Dwivedi, Prabhat Ranjan Mishra, Gopal Gupta, Satish Agrawal, Vikas Sharma, Jagdamba P. Maikhuri |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_treatment
Antineoplastic Agents Apoptosis 02 engineering and technology Pharmacology Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Breast cancer chemotherapy Polylactic Acid-Polyglycolic Acid Copolymer Structural Biology medicine Animals Humans Lactic Acid Oleanolic Acid Particle Size Molecular Biology Oleanolic acid Bioenhancer Chitosan Drug Carriers Mammary tumor General Medicine 021001 nanoscience & nanotechnology medicine.disease Rats Enzyme Activation Drug Liberation Fertility chemistry Caspases 030220 oncology & carcinogenesis Toxicity Nanoparticles Female Nanocarriers 0210 nano-technology Polyglycolic Acid |
| Zdroj: | International Journal of Biological Macromolecules. 104:1345-1358 |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2017.06.005 |
| Popis: | Addressing multidrug resistant stage of breast cancer is an impediment for chemotherapy. Moreover, breast cancer chemotherapy has potential enduring confrontations i.e. related toxicity including effect on fertility of young female patients. The co-delivery of polyphenolic bio-enhancers with oleanolic acid in chitosan coated PLGA nanoparticles was designed for oral delivery with enhanced antitumor effect consecutively preserving the female fertility. The optimized oleanolic- bio-enhancer nano formulation CH-OA-B-PLGA with particle size was 342.2±3.7nm and zeta potential of 34.2±3.1mV was capable of lowering viability in MDAMB 231 cell line 16 times than OA. Further, mechanistic studies in MDAMB-231 cells revealed that CH-OA-PLGA induces apoptosis by mitochondrial membrane disruption; follows ROS mediated and caspase dependent apoptosis. The antitumor effect studied in 4-T1 induced Balb/c mice mammary tumor model displayed augmented antitumor potency by CH-OA-B-PLGA in comparison to OA. In the in vivo toxicity on Sprague-Dawley rat model, CH-OA-B-PLGA significantly displayed the safe profile and also preserves fertility in female rats. The experiment result suggests co-delivery of oleanolic acid with bio-enhancers as a breakthrough for developing safe chemotherapy for hormone independent breast cancer therapy countering the toxicity issues. |
| Databáze: | OpenAIRE |
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