Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics.
The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano-carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer.
Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
Neeraj K
NK
Garg
Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India; UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160 014, India.
Bhupinder
B
Singh
Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
Ashay
A
Jain
Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India.
Pradip
P
Nirbhavane
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar 470003, M.P., India.
Rajeev
R
Sharma
Department of Periodontics, College of Dental Medicine, Georgia Regents University, Augusta, GA 30912, USA; Institute of Science, Nirma University, Sarkhej-Gandhinagar highway, Ahmedabad 382481, India. Electronic address: rajeev.gru@gmail.com.
Rajeev K
RK
Tyagi
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research(NIPER), Punjab 160062, India.
Varun
V
Kushwah
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research(NIPER), Punjab 160062, India.
Sanyog
S
Jain
Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India. Electronic address: drkatare@yahoo.com.
Om Prakash
OP
Katare
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005643:Fucose / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D008055:Lipids; D005643:Fucose; D008727:Methotrexate
Breast cancer; Fucose; Gelucire(®) 50/13; Methotrexate; Phospholipid 90NG; Solid lipid nanoparticles; Stearic acid; Targeted delivery