Combinatorial Synthesis of New Cationic Lipids and High-Throughput Screening of Their Transfection Properties

Further Studies on Cationic Gemini Amphiphiles as Carriers for Gene Delivery─The Effect of Linkers in the Structure and Other Factors Affecting the Transfection Efficacy of These Amphiphiles

“…Cholesterol is reported to confer serum compatibility to the vectors used for delivery of genes. 55 Keeping this report in mind, it was planned to incorporate cholesterol in the lipoplex formulations of the synthesized GAs and evaluate their transfection efficacies in the absence and in the presence of serum (10% FBS). Cholesterol was incorporated into the formulations in two different ratios [GA/DOPE/cholesterol in the ratio of 1:1:1 Formulation (d), and 1:1:0.5 Formulation (e)].…”

“…Cholesterol is reported to confer serum compatibility to the vectors used for delivery of genes . Keeping this report in mind, it was planned to incorporate cholesterol in the lipoplex formulations of the synthesized GAs and evaluate their transfection efficacies in the absence and in the presence of serum (10% FBS).…”

Further Studies on Cationic Gemini Amphiphiles as Carriers for Gene Delivery─The Effect of Linkers in the Structure and Other Factors Affecting the Transfection Efficacy of These Amphiphiles

“…Cholesterol is reported to confer serum compatibility to the vectors used for delivery of genes. 55 Keeping this report in mind, it was planned to incorporate cholesterol in the lipoplex formulations of the synthesized GAs and evaluate their transfection efficacies in the absence and in the presence of serum (10% FBS). Cholesterol was incorporated into the formulations in two different ratios [GA/DOPE/cholesterol in the ratio of 1:1:1 Formulation (d), and 1:1:0.5 Formulation (e)].…”

“…Cholesterol is reported to confer serum compatibility to the vectors used for delivery of genes . Keeping this report in mind, it was planned to incorporate cholesterol in the lipoplex formulations of the synthesized GAs and evaluate their transfection efficacies in the absence and in the presence of serum (10% FBS).…”

Combinatorial Synthesis of a Lipidoid Library by Thiolactone Chemistry: In Vitro Screening and In Vivo Validation for siRNA Delivery

“…With respect to the tail, two (T18U-PY18-A4 and T18U-PY12-A17) of the three top-performing lipidoids possessed one unsaturated tail from the thiolactone contribution and one shorter chain (C12) from the pyridyl moiety (refer to Scheme for the structure). Previously, our group and others have reported that shorter chain or unsaturated chain tails enhance transfection efficiency. − The superior performance of unsaturated hydrophobic tails might be attributed to the restricted chain flexibility, permitting enhanced interaction with lipids from the cell membrane. Regarding amine head groups in the top-performing lipidoids, the N,N -dimethyl ethylene diamine group present in T18U-PY12-A17 and T16-PY12-A17 and the 1-(2-aminoethyl) pyrrolidine group in T18U-PY18-A4 were found to play an important role in efficient transfection, which is consistent with previous reports .…”

Gemini Amphiphile-Based Lipoplexes for Efficient Gene Delivery: Synthesis, Formulation Development, Characterization, Gene Transfection, and Biodistribution Studies

“…Serum is known to decrease the transfection efficacy of a gene delivery carrier, whereas cholesterol is known to impart serum compatibility to gene delivery carriers. 50 For improving the transfection efficacy of the synthesized GAs in serum, cholesterol was also incorporated in the GA formulations in two different molar ratios, i.e., GA/DOPE/cholesterol in the ratios of 1:1:1 and 1:1:0.5. Three standard formulations, DOTAP/DOPE (1.37 mU), DCC/DOPE (1.68 mU), and Lipofectamine 2000 (2.07 mU), alone were used as positive controls.…”

“…Cholesterol is known to impart serum compatibility to gene delivery carriers. 50 In our quest to improve transfection efficacies in the presence of serum, GAs exhibiting the best results ( 5b and 5d ) were reformulated to include cholesterol. New formulations were prepared to include two different concentrations of cholesterol in the ratios such as GA/DOPE/cholesterol of 1:1:1 and 1:1:0.5.…”

Further Studies on Cationic Gemini Amphiphiles as Carriers for Gene Delivery─The Effect of Linkers in the Structure and Other Factors Affecting the Transfection Efficacy of These Amphiphiles

“…Cholesterol is reported to confer serum compatibility to the vectors used for delivery of genes. 55 Keeping this report in mind, it was planned to incorporate cholesterol in the lipoplex formulations of the synthesized GAs and evaluate their transfection efficacies in the absence and in the presence of serum (10% FBS). Cholesterol was incorporated into the formulations in two different ratios [GA/DOPE/cholesterol in the ratio of 1:1:1 Formulation (d), and 1:1:0.5 Formulation (e)].…”

“…Cholesterol is reported to confer serum compatibility to the vectors used for delivery of genes . Keeping this report in mind, it was planned to incorporate cholesterol in the lipoplex formulations of the synthesized GAs and evaluate their transfection efficacies in the absence and in the presence of serum (10% FBS).…”

Combinatorial Synthesis of a Lipidoid Library by Thiolactone Chemistry: In Vitro Screening and In Vivo Validation for siRNA Delivery

“…With respect to the tail, two (T18U-PY18-A4 and T18U-PY12-A17) of the three top-performing lipidoids possessed one unsaturated tail from the thiolactone contribution and one shorter chain (C12) from the pyridyl moiety (refer to Scheme for the structure). Previously, our group and others have reported that shorter chain or unsaturated chain tails enhance transfection efficiency. − The superior performance of unsaturated hydrophobic tails might be attributed to the restricted chain flexibility, permitting enhanced interaction with lipids from the cell membrane. Regarding amine head groups in the top-performing lipidoids, the N,N -dimethyl ethylene diamine group present in T18U-PY12-A17 and T16-PY12-A17 and the 1-(2-aminoethyl) pyrrolidine group in T18U-PY18-A4 were found to play an important role in efficient transfection, which is consistent with previous reports .…”

Gemini Amphiphile-Based Lipoplexes for Efficient Gene Delivery: Synthesis, Formulation Development, Characterization, Gene Transfection, and Biodistribution Studies

“…Serum is known to decrease the transfection efficacy of a gene delivery carrier, whereas cholesterol is known to impart serum compatibility to gene delivery carriers. 50 For improving the transfection efficacy of the synthesized GAs in serum, cholesterol was also incorporated in the GA formulations in two different molar ratios, i.e., GA/DOPE/cholesterol in the ratios of 1:1:1 and 1:1:0.5. Three standard formulations, DOTAP/DOPE (1.37 mU), DCC/DOPE (1.68 mU), and Lipofectamine 2000 (2.07 mU), alone were used as positive controls.…”

“…Cholesterol is known to impart serum compatibility to gene delivery carriers. 50 In our quest to improve transfection efficacies in the presence of serum, GAs exhibiting the best results ( 5b and 5d ) were reformulated to include cholesterol. New formulations were prepared to include two different concentrations of cholesterol in the ratios such as GA/DOPE/cholesterol of 1:1:1 and 1:1:0.5.…”

Further Studies on Cationic Gemini Amphiphiles as Carriers for Gene Delivery─The Effect of Linkers in the Structure and Other Factors Affecting the Transfection Efficacy of These Amphiphiles

“…Cholesterol is reported to confer serum compatibility to the vectors used for delivery of genes. 55 Keeping this report in mind, it was planned to incorporate cholesterol in the lipoplex formulations of the synthesized GAs and evaluate their transfection efficacies in the absence and in the presence of serum (10% FBS). Cholesterol was incorporated into the formulations in two different ratios [GA/DOPE/cholesterol in the ratio of 1:1:1 Formulation (d), and 1:1:0.5 Formulation (e)].…”

“…Cholesterol is reported to confer serum compatibility to the vectors used for delivery of genes . Keeping this report in mind, it was planned to incorporate cholesterol in the lipoplex formulations of the synthesized GAs and evaluate their transfection efficacies in the absence and in the presence of serum (10% FBS).…”

Combinatorial Synthesis of a Lipidoid Library by Thiolactone Chemistry: In Vitro Screening and In Vivo Validation for siRNA Delivery

“…With respect to the tail, two (T18U-PY18-A4 and T18U-PY12-A17) of the three top-performing lipidoids possessed one unsaturated tail from the thiolactone contribution and one shorter chain (C12) from the pyridyl moiety (refer to Scheme for the structure). Previously, our group and others have reported that shorter chain or unsaturated chain tails enhance transfection efficiency. − The superior performance of unsaturated hydrophobic tails might be attributed to the restricted chain flexibility, permitting enhanced interaction with lipids from the cell membrane. Regarding amine head groups in the top-performing lipidoids, the N,N -dimethyl ethylene diamine group present in T18U-PY12-A17 and T16-PY12-A17 and the 1-(2-aminoethyl) pyrrolidine group in T18U-PY18-A4 were found to play an important role in efficient transfection, which is consistent with previous reports .…”

Gemini Amphiphile-Based Lipoplexes for Efficient Gene Delivery: Synthesis, Formulation Development, Characterization, Gene Transfection, and Biodistribution Studies

“…Serum is known to decrease the transfection efficacy of a gene delivery carrier, whereas cholesterol is known to impart serum compatibility to gene delivery carriers. 50 For improving the transfection efficacy of the synthesized GAs in serum, cholesterol was also incorporated in the GA formulations in two different molar ratios, i.e., GA/DOPE/cholesterol in the ratios of 1:1:1 and 1:1:0.5. Three standard formulations, DOTAP/DOPE (1.37 mU), DCC/DOPE (1.68 mU), and Lipofectamine 2000 (2.07 mU), alone were used as positive controls.…”

“…Cholesterol is known to impart serum compatibility to gene delivery carriers. 50 In our quest to improve transfection efficacies in the presence of serum, GAs exhibiting the best results ( 5b and 5d ) were reformulated to include cholesterol. New formulations were prepared to include two different concentrations of cholesterol in the ratios such as GA/DOPE/cholesterol of 1:1:1 and 1:1:0.5.…”