title: In vitro control release, cytotoxicity assessment and cellular uptake of methotrexate loaded liquid-crystalline folate nanocarrier.
abstract: Folate molecules self-assemble in the form of stacks to form liquid-crystalline solutions. Nanocarriers from self-assembled folates are composed of highly ordered structures, which offer high encapsulation of drug (95-98%), controlled drug release rates, active cellular uptake and biocompatibility. Recently, we have shown that the release rates of methotrexate can be controlled by varying the size of nanoparticles, cross-linking cation and cross-linking concentration. The present study reports the in vitro cytotoxic behavior of methotrexate loaded liquid-crystalline folate nanoparticles on cultured HeLa cells. Changing drug release rates can influence cytotoxicity of cancer cells. Therefore, to study the correlation of release rate and cytotoxic behavior, the effect of release controlling parameters on HeLa cells was studied through MTT assay. It is reported that by controlling the methotrexate release, the survival rates of HeLa cells can be controlled. Released methotrexate kills HeLa cells as effectively as free methotrexate solution. The co-culture based in vitro cellular uptake study through fluorescence microscopy on folate receptor positive and negative cancer cells shows that the present nanocarrier has the potential to distinguish cancer cells from normal cells. Overall, the present study reports the in vitro performance of self-assembled liquid-crystalline folate nanoparticles, which will be a platform for further in vivo studies and clinical trials.
authors: Advance Materials & Nanoscience Laboratory, Department of Chemical Engineering, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi 110016, India. Electronic address: biotech.rahul.mishra@gmail.com.
authors: Rahul
authors: R
authors: Misra
authors: Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi 110016, India.
authors: Mohita
authors: M
authors: Upadhyay
authors: Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi 110016, India.
authors: Vivekanandan
authors: V
authors: Perumal
authors: Advance Materials & Nanoscience Laboratory, Department of Chemical Engineering, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi 110016, India.
authors: Sanat
authors: S
authors: Mohanty
mesh_terms: D000818:Animals; D002412:Cations; D016923:Cell Death / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D005453:Fluorescence; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry; D008027:Light; D050866:Liquid Crystals / Q000737:chemistry*; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D012542:Scattering, Radiation
chemical_list: D002412:Cations; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D065347:Hypromellose Derivatives; D005492:Folic Acid; D008727:Methotrexate
keywords: Cellular uptake; Chromonics; Cytotoxicity; Folate nanoparticles; Liquid-crystalline; Self-assembly