The ligand (s) anchored lipobrid nanoconstruct mediated delivery of methotrexate: an effective approach in breast cancer therapeutics

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• 作者：Neeraj K. Garg ; MPharm^a ; Bhupinder Singh ; PhD^a ; ^b ; Varun Kushwah ; MPharm^c ; Rajeev K. Tyagi ; PhD^d ; ^{rajeev.gru@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; ^{rajeev.gru@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Rajeev Sharma ; MPharm^e ; Sanyog Jain ; PhD^c ; Om Prakash Katare ; PhD^a ; ^{drkatare@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MTX ; methotrexate ; F ; fucose ; G ; gaalactose ; M ; mannose ; NPs ; nanoparticles ; EPR ; enhanced permeation and retention ; PL S100 ; Phospholipon S100 ; PCL ; polycaprolactone ; C-6 ; coumarin-6 ; DMF ; dimethyl formamide ; DCM ; dichloromethane ; PDI ; Polydispersity Index ; HR-TEM ; high resolution transmission electron microscope ; CLSM ; confocal laser scanning microscopy ; EBr ; ethidium bromide ; AO ; acridine orange ; LMP ; lysosomal membrane permeability ; AUC ; area under the curve ; Cmax ; maximum plasma concentrati
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：12
• 期：7
• 页码：2043-2060
• 全文大小：3307 K

文摘

The present study was designed to engineer surface-anchored and methotrexate loaded lipobrid nano-constructs for targeting breast cancer. Ligands (fucose, galactose and mannose) anchored lipobrid nano-constructs were used to compare and assess delivery efficiency in breast cancer cell lines as well as in DMBA induced breast cancer animal model. The developed and characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, bio-distribution, changes in tumor volume and animal survival. Our results show greater cellular uptake, cytotoxicity at low IC50, apoptosis with altered lysosomal membrane permeability and greater rate of degradation of lysosomal membrane. We saw better bioavailability and tumor targeting efficiency with minimum secondary organ drug distribution. The significant reduction was seen in tumor burden with ligand anchored lipobrids in comparison to plain and MTX-lipobrid formulations. In conclusion, fucose anchored MTX-lipobrid formulation showed promising results, and warrants to explore the development of therapeutic interventions for breast cancer.