title: An anti-oxidant, α-lipoic acid conjugated oleoyl-sn-phosphatidylcholineas a helper lipid in cationic liposomal formulations.
abstract: Development of safe non-viral carrier systems for efficient intra-cellular delivery of drugs and genes hold promise in the area of translational research. Liposome based delivery systems have emerged as one of the attractive strategies for efficient delivery of drugs and nucleic acids. To this end, number of investigations was carried on liposomal formulations using lipids for achieving higher efficiency in transfection with lower cytotoxicities. In our efforts to develop safer and efficient liposomal delivery systems, we synthesized a novel anti-oxidant lipid, α-lipoyl, oleyl-sn-phosphatidylcholine (LOPC) and used as a helper lipid in combination with a cationic amphiphile, Di-Stearyl Dihydroxy Ethyl Ammonium Chloride (DSDEAC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at varying concentrations of LOPC. DNA binding properties of the liposomal formulations (DS, DS LA1, DS LA2 and DS LA3) revealed that increasing the percentage of single aliphatic chain lipid LOPC, did not affect the DNA binding properties. But, transfection profiles of these liposomal formulations in 3 different cell lines (HeLa, HEK 293 and MCF7) showed difference in their efficacies. Results showed that optimal percentage of LOPC i.e. 25% in DSDEAC and DOPC at 1:1 molar ratio (DS LA1) enhanced transfection as compared to DSDEAC:DOPC alone. The endosomal escape studies with NBD labelled lysotracker and Rhodamine labelled liposomal formulations revealed that DS LA1 and DS LA2 facilitated the release of genetic cargo with a better efficiency than their counter parts. Reactive Oxygen Species (ROS), a key modulator of necroptosis were lowered with the treatment of DS LA1 than other liposomal formulations. Here in, we present a novel liposomal formulation using DSDEAC and DOPC at 1:1 molar ratio doped with 25-50% (mole ratio) LOPC as an efficient delivery system for enhanced transfection with quenching of ROS levels compared to formulations without LOPC.
authors.affiliation: Centre for Stem Cell Research (CSCR), (A Unit of inStem, Bengaluru), Christian Medical College Campus, Bagayam, Vellore 632002, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Dharmalingam
authors.affiliation: Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: Balakrishna
authors.initials: B
authors.lastname: Marrapu
authors.affiliation: BioSatva Technologies, Golnaka, Hyderabad 500013, India.
authors.forename: Chandrashekhar
authors.initials: C
authors.lastname: Voshavar
authors.affiliation: Centre for Stem Cell Research (CSCR), (A Unit of inStem, Bengaluru), Christian Medical College Campus, Bagayam, Vellore 632002, India.
authors.forename: Rasagna
authors.initials: R
authors.lastname: Nadella
authors.affiliation: Centre for Stem Cell Research (CSCR), (A Unit of inStem, Bengaluru), Christian Medical College Campus, Bagayam, Vellore 632002, India.
authors.forename: Vignesh Kumar
authors.initials: VK
authors.lastname: Rangasami
authors.affiliation: Centre for Stem Cell Research (CSCR), (A Unit of inStem, Bengaluru), Christian Medical College Campus, Bagayam, Vellore 632002, India; Department of Haematology, Christian Medical College Hospital, Vellore 6302002, Tamilnadu, India.
authors.forename: R V
authors.initials: RV
authors.lastname: Shaji
authors.affiliation: Centre for Stem Cell Research (CSCR), (A Unit of inStem, Bengaluru), Christian Medical College Campus, Bagayam, Vellore 632002, India.
authors.forename: Salar
authors.initials: S
authors.lastname: Abbas
authors.affiliation: Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors.forename: R B N
authors.initials: RBN
authors.lastname: Prasad
authors.affiliation: Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address: Shivashanker.kaki@iict.res.in.
authors.forename: Shiva Shanker
authors.initials: SS
authors.lastname: Kaki
authors.affiliation: Centre for Stem Cell Research (CSCR), (A Unit of inStem, Bengaluru), Christian Medical College Campus, Bagayam, Vellore 632002, India. Electronic address: Srujankm@cmcvellore.ac.in.
authors.forename: Srujan
authors.initials: S
authors.lastname: Marepally
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D010713:Phosphatidylcholines / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000737:chemistry*; D014162:Transfection
chemical_list: D000975:Antioxidants; D008081:Liposomes; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; D008063:Thioctic Acid
keywords: Anti-oxidant; Cationic amphiphile; Lipoic acid; Phosphatidylcholine; Transfection