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Functionalized lipid polymer hybrid nanoparticles mediated codelivery of methotrexate & aceclofenac: A synergistic effect in breast cancer with improved pharmacokinetics attributes Neeraj K. Garg, Rajeev K. Tyagi, Gajanand Sharma, Ashay Jain, Bhupinder Singh, Sanyog Jain, and O. P. Katare Mol. Pharmaceutics, Just Accepted Manuscript • DOI: 10.1021/acs.molpharmaceut.6b01148 • Publication Date (Web): 12 Apr 2017 Downloaded from http://pubs.acs.org on April 12, 2017
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Molecular Pharmaceutics
Functionalized lipid polymer hybrid nanoparticles mediated co-delivery of methotrexate & aceclofenac: A synergistic effect in breast cancer with improved pharmacokinetics attributes Neeraj K. Garg1, Rajeev K. Tyagi2, Gajanand Sharma1, Ashay Jain1, Bhupinder Singh1, 3, Sanyog Jain4, O.P. Katare*1 1University
2Institute
Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh 160014, India
of Science, Nirma University, SG Highway, Ahmedabad, Gujarat, 382481 India
3UGC-Centre
of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh 160 014, India 4Centre
for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar (Mohali), Punjab 160062, India
*To whom correspondence should be addressed Prof. Om Prakash Katare University Institute of Pharmaceutical Sciences UGC-Centre of Advanced Study, Panjab University, Chandigarh 160 014, India E-mail:
[email protected] +91 172 2534103, Fax: +91 172 2543101
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Molecular Pharmaceutics
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Abstract Present study was aimed to co-encapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose anchored lipid-polymer hybrid nanoparticles (Fu-LPHNPs) to achieving target specific and controlled delivery for developing therapeutic interventions against breast cancer. The effective combination therapy requires co-administration of drugs to achieving synergistic effect on tumor with minimum adverse effects. Present study investigates the potential of co-delivery of MTX & ACL through LPHNPs in MCF-7 and triple negative breast cancer cells (MDA-MB-231) to reduce the adverse effects. We obtained LPHNPs in the nano-size range (0.05) effect on cell viability when estimated with both cells at all concentrations (0.01-20µg/mL) tested. However, co-encapsulation of ACL with MTX (MTX+ACL, LPHNPS-(MTX+ACL)) and fucose anchoring showed a decrease in cell viability in both cells. MCF-7 & MDA-MB-231 cells were shown more sensitive when treated with ACL in combination with MTX than that seen with free MTX. The increased synergistic cytotoxic effect of MTX37-40 and ACL was seen with MTX and ACL co-encapsulated in fucose functionalized LPHNPs. The greater cytotoxicity rendered by co-administration of MTX and ACL delivered through fucose functionalized LPHNPs is led by the ligand receptor mediated internalization.
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Molecular Pharmaceutics
Cytotoxic response of MTX & ACL co-encapsulated NPs saw an proportional increase with
an
increase
in
drug
concentration
in
the
following
order:
MTX
