The Experts below are selected from a list of 12093 Experts worldwide ranked by ideXlab platform

Udo Bakowsky - One of the best experts on this subject based on the ideXlab platform.

  • composite liposome pei nucleic acid lipopolyplexes for safe and efficient Gene delivery and Gene Knockdown
    Colloids and Surfaces B: Biointerfaces, 2017
    Co-Authors: Shashank Reddy Pinnapireddy, Lili Duse, Boris Strehlow, Jens Schafer, Udo Bakowsky
    Abstract:

    Abstract Cytotoxicity is a major drawback impeding the therapeutic use of Gene delivery and Gene down-regulation vehicles. Apart from cytotoxicity, rapid degradation and low cellular uptake are other major factors affecting therapeutic use. Considering the above factors, formulation and development of PEI (Polyethylenimine) based, liposome encapsulated delivery vehicles with improved transfection efficiency and low cytotoxicity which can be used for Gene delivery and Gene Knockdown. DOPE (1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine), DPPC (Dipalmitoylphosphatidylcholine) and cholesterol have been considered as lipids of choice bearing in mind various factors such as rigidness and surface charge which greatly influence the formation of liposomes, polyplex encapsulation and transfection efficiency. For the condensation of plasmid DNA (pDNA) and short interfering RNA (siRNA), branched PEI 25 kDa (bPEI) and deacylated linear PEI 22 kDa (lPEI) were employed. lPEI and siRNA polyplexes encapsulated within DOPE/DPPC/Cholesterol (DDC) liposomes exhibited higher luc (luciferase) Gene Knockdown in vitro compared to the controls. They also showed superior transfection efficiencies compared to polyplexes in experiments using pCMV-luc (luciferase reporter plasmid) and pEGFP-N1 (Green Fluorescence protein reporter plasmid). This can partly be attributed to the improved integrity imparted by the liposomal layer which was confirmed by complex stability and integrity assays. Cytotoxicity and coagulation time assays of DDC-lPEI based lipopolyplexes showed decreased cytotoxic potential and negligible influence on coagulation respectively for compared to polyplexes, thus rendering them suitable for Gene therapy.

  • Composite liposome-PEI/nucleic acid lipopolyplexes for safe and efficient Gene delivery and Gene Knockdown
    Colloids and Surfaces B: Biointerfaces, 2017
    Co-Authors: Shashank Reddy Pinnapireddy, Lili Duse, Boris Strehlow, Jens Schafer, Udo Bakowsky
    Abstract:

    Abstract Cytotoxicity is a major drawback impeding the therapeutic use of Gene delivery and Gene down-regulation vehicles. Apart from cytotoxicity, rapid degradation and low cellular uptake are other major factors affecting therapeutic use. Considering the above factors, formulation and development of PEI (Polyethylenimine) based, liposome encapsulated delivery vehicles with improved transfection efficiency and low cytotoxicity which can be used for Gene delivery and Gene Knockdown. DOPE (1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine), DPPC (Dipalmitoylphosphatidylcholine) and cholesterol have been considered as lipids of choice bearing in mind various factors such as rigidness and surface charge which greatly influence the formation of liposomes, polyplex encapsulation and transfection efficiency. For the condensation of plasmid DNA (pDNA) and short interfering RNA (siRNA), branched PEI 25 kDa (bPEI) and deacylated linear PEI 22 kDa (lPEI) were employed. lPEI and siRNA polyplexes encapsulated within DOPE/DPPC/Cholesterol (DDC) liposomes exhibited higher luc (luciferase) Gene Knockdown in vitro compared to the controls. They also showed superior transfection efficiencies compared to polyplexes in experiments using pCMV-luc (luciferase reporter plasmid) and pEGFP-N1 (Green Fluorescence protein reporter plasmid). This can partly be attributed to the improved integrity imparted by the liposomal layer which was confirmed by complex stability and integrity assays. Cytotoxicity and coagulation time assays of DDC-lPEI based lipopolyplexes showed decreased cytotoxic potential and negligible influence on coagulation respectively for compared to polyplexes, thus rendering them suitable for Gene therapy.

M Aslam - One of the best experts on this subject based on the ideXlab platform.

  • α mannosyl functionalized cationic nanohydrogel particles for targeted Gene Knockdown in immunosuppressive macrophages
    Macromolecular Bioscience, 2019
    Co-Authors: Nadine Leber, L Kaps, M Aslam, Aiting Yang, Mariacristina Giardino, A Klefenz, N Choteschovsky, Sebastian Rosigkeit, Asmaa Mostafa
    Abstract:

    : Immunosuppressive M2 macrophages govern the immunophathogenic micromilieu in many severe diseases including cancer or fibrosis, thus, their re-polarization through RNA interference is a promising concept to support combinatorial therapies. For targeted siRNA delivery, however, safe and stable carriers are required that manage cell specific transport to M2 macrophages. Here, siRNA-loaded cationic nanogels are reported with α-mannosyl decorated surfaces that target and modify M2 macrophages selectively. Via amphiphilic precursor block copolymers bearing one single α-mannosyl moiety at their chain end mannosylated cationic nanohydrogel particles (ManNP) were obtained of 20 nm diameter determined by dynamic light scattering and cryogenic electron transmission microscopy. α-Mannosyl surface modification is confirmed by agglutination with concanavalin A. SiRNA-loaded ManNP preferentially targets the overexpressed mannose receptor CD206 on M2 macrophages, as shown by in vitro cell uptake studies in M2 polarized primary macrophages. This specificity is confirmed, since ManNP uptake could be reduced by blocking of CD206 with mannan. Effective ManNP-guided siRNA delivery is confirmed by sequence-specific Gene Knockdown of CSF-1R in M2-type macrophages exclusively, while the expression levels in M1-polarized macrophages is not affected. In conclusion, α-mannosyl-functionalized ManNPs are promising universal siRNA carriers for targeted immunomodulatory treatment of immunosuppressive macrophages.

  • α‐Mannosyl‐Functionalized Cationic Nanohydrogel Particles for Targeted Gene Knockdown in Immunosuppressive Macrophages
    Macromolecular Bioscience, 2019
    Co-Authors: Nadine Leber, L Kaps, M Aslam, Aiting Yang, Mariacristina Giardino, A Klefenz, N Choteschovsky, Sebastian Rosigkeit, Asmaa Mostafa, Lutz Nuhn
    Abstract:

    Immunosuppressive M2 macrophages govern the immunophathogenic micromilieu in many severe diseases including cancer or fibrosis, thus, their re-polarization through RNA interference is a promising concept to support combinatorial therapies. For targeted siRNA delivery, however, safe and stable carriers are required that manage cell specific transport to M2 macrophages. Here, siRNA-loaded cationic nanogels are reported with α-mannosyl decorated surfaces that target and modify M2 macrophages selectively. Via amphiphilic precursor block copolymers bearing one single α-mannosyl moiety at their chain end mannosylated cationic nanohydrogel particles (ManNP) were obtained of 20 nm diameter determined by dynamic light scattering and cryogenic electron transmission microscopy. α-Mannosyl surface modification is confirmed by agglutination with concanavalin A. SiRNA-loaded ManNP preferentially targets the overexpressed mannose receptor CD206 on M2 macrophages, as shown by in vitro cell uptake studies in M2 polarized primary macrophages. This specificity is confirmed, since ManNP uptake could be reduced by blocking of CD206 with mannan. Effective ManNP-guided siRNA delivery is confirmed by sequence-specific Gene Knockdown of CSF-1R in M2-type macrophages exclusively, while the expression levels in M1-polarized macrophages is not affected. In conclusion, α-mannosyl-functionalized ManNPs are promising universal siRNA carriers for targeted immunomodulatory treatment of immunosuppressive macrophages.

  • sirna mediated in vivo Gene Knockdown by acid degradable cationic nanohydrogel particles
    Journal of Controlled Release, 2017
    Co-Authors: Nadine Leber, L Kaps, M Aslam, Jonathan Schupp, A Brose, David Schaffel, Karl Fischer, Mustafa Diken, Dennis Strand
    Abstract:

    Abstract Cationic nanohydrogel particles have become an attractive tool for systemic siRNA delivery, but improvement of their in vivo tolerance is desirable, especially to prevent potential long term side effects by tissue and cellular accumulation. Here, we designed novel ketal cross-linked cationic nanohydrogel particles that were assessed for reduced tissue accumulation and robust siRNA delivery in vitro and in vivo . An oligo-amine cross-linker equipped with a ketal moiety in its core was synthesized and applied to nanohydrogel cross-linking of self-assembled reactive ester block copolymers in DMSO. The resulting acid-sensitive cationic nanoparticles spontaneously disassembled over time in acidic milieu, as investigated by dynamic light scattering. Fluorescent correlation spectroscopy showed effective complexation with siRNA as well as its release upon particle degradation at endosomal pH. These properties resulted in an enhanced in vitro Gene Knockdown for the acid-degradable cationic nanoparticles compared to their non-degradable spermine analogues. In a murine liver fibrosis model enhanced carrier and payload accumulation in the fibrotic tissue facilitated sequence-specific Gene Knockdown and prevented fibrosis progression. Long-term monitoring of the carrier in the body showed an enhanced clearance for the acid-degradable carrier, even after multiple dosing. Therefore, these acid-degradable cationic nanohydrogel particles can be considered as promising siRNA carriers for in vivo purposes towards therapeutic applications.

Nadine Leber - One of the best experts on this subject based on the ideXlab platform.

  • α mannosyl functionalized cationic nanohydrogel particles for targeted Gene Knockdown in immunosuppressive macrophages
    Macromolecular Bioscience, 2019
    Co-Authors: Nadine Leber, L Kaps, M Aslam, Aiting Yang, Mariacristina Giardino, A Klefenz, N Choteschovsky, Sebastian Rosigkeit, Asmaa Mostafa
    Abstract:

    : Immunosuppressive M2 macrophages govern the immunophathogenic micromilieu in many severe diseases including cancer or fibrosis, thus, their re-polarization through RNA interference is a promising concept to support combinatorial therapies. For targeted siRNA delivery, however, safe and stable carriers are required that manage cell specific transport to M2 macrophages. Here, siRNA-loaded cationic nanogels are reported with α-mannosyl decorated surfaces that target and modify M2 macrophages selectively. Via amphiphilic precursor block copolymers bearing one single α-mannosyl moiety at their chain end mannosylated cationic nanohydrogel particles (ManNP) were obtained of 20 nm diameter determined by dynamic light scattering and cryogenic electron transmission microscopy. α-Mannosyl surface modification is confirmed by agglutination with concanavalin A. SiRNA-loaded ManNP preferentially targets the overexpressed mannose receptor CD206 on M2 macrophages, as shown by in vitro cell uptake studies in M2 polarized primary macrophages. This specificity is confirmed, since ManNP uptake could be reduced by blocking of CD206 with mannan. Effective ManNP-guided siRNA delivery is confirmed by sequence-specific Gene Knockdown of CSF-1R in M2-type macrophages exclusively, while the expression levels in M1-polarized macrophages is not affected. In conclusion, α-mannosyl-functionalized ManNPs are promising universal siRNA carriers for targeted immunomodulatory treatment of immunosuppressive macrophages.

  • α‐Mannosyl‐Functionalized Cationic Nanohydrogel Particles for Targeted Gene Knockdown in Immunosuppressive Macrophages
    Macromolecular Bioscience, 2019
    Co-Authors: Nadine Leber, L Kaps, M Aslam, Aiting Yang, Mariacristina Giardino, A Klefenz, N Choteschovsky, Sebastian Rosigkeit, Asmaa Mostafa, Lutz Nuhn
    Abstract:

    Immunosuppressive M2 macrophages govern the immunophathogenic micromilieu in many severe diseases including cancer or fibrosis, thus, their re-polarization through RNA interference is a promising concept to support combinatorial therapies. For targeted siRNA delivery, however, safe and stable carriers are required that manage cell specific transport to M2 macrophages. Here, siRNA-loaded cationic nanogels are reported with α-mannosyl decorated surfaces that target and modify M2 macrophages selectively. Via amphiphilic precursor block copolymers bearing one single α-mannosyl moiety at their chain end mannosylated cationic nanohydrogel particles (ManNP) were obtained of 20 nm diameter determined by dynamic light scattering and cryogenic electron transmission microscopy. α-Mannosyl surface modification is confirmed by agglutination with concanavalin A. SiRNA-loaded ManNP preferentially targets the overexpressed mannose receptor CD206 on M2 macrophages, as shown by in vitro cell uptake studies in M2 polarized primary macrophages. This specificity is confirmed, since ManNP uptake could be reduced by blocking of CD206 with mannan. Effective ManNP-guided siRNA delivery is confirmed by sequence-specific Gene Knockdown of CSF-1R in M2-type macrophages exclusively, while the expression levels in M1-polarized macrophages is not affected. In conclusion, α-mannosyl-functionalized ManNPs are promising universal siRNA carriers for targeted immunomodulatory treatment of immunosuppressive macrophages.

  • sirna mediated in vivo Gene Knockdown by acid degradable cationic nanohydrogel particles
    Journal of Controlled Release, 2017
    Co-Authors: Nadine Leber, L Kaps, M Aslam, Jonathan Schupp, A Brose, David Schaffel, Karl Fischer, Mustafa Diken, Dennis Strand
    Abstract:

    Abstract Cationic nanohydrogel particles have become an attractive tool for systemic siRNA delivery, but improvement of their in vivo tolerance is desirable, especially to prevent potential long term side effects by tissue and cellular accumulation. Here, we designed novel ketal cross-linked cationic nanohydrogel particles that were assessed for reduced tissue accumulation and robust siRNA delivery in vitro and in vivo . An oligo-amine cross-linker equipped with a ketal moiety in its core was synthesized and applied to nanohydrogel cross-linking of self-assembled reactive ester block copolymers in DMSO. The resulting acid-sensitive cationic nanoparticles spontaneously disassembled over time in acidic milieu, as investigated by dynamic light scattering. Fluorescent correlation spectroscopy showed effective complexation with siRNA as well as its release upon particle degradation at endosomal pH. These properties resulted in an enhanced in vitro Gene Knockdown for the acid-degradable cationic nanoparticles compared to their non-degradable spermine analogues. In a murine liver fibrosis model enhanced carrier and payload accumulation in the fibrotic tissue facilitated sequence-specific Gene Knockdown and prevented fibrosis progression. Long-term monitoring of the carrier in the body showed an enhanced clearance for the acid-degradable carrier, even after multiple dosing. Therefore, these acid-degradable cationic nanohydrogel particles can be considered as promising siRNA carriers for in vivo purposes towards therapeutic applications.

Shashank Reddy Pinnapireddy - One of the best experts on this subject based on the ideXlab platform.

  • composite liposome pei nucleic acid lipopolyplexes for safe and efficient Gene delivery and Gene Knockdown
    Colloids and Surfaces B: Biointerfaces, 2017
    Co-Authors: Shashank Reddy Pinnapireddy, Lili Duse, Boris Strehlow, Jens Schafer, Udo Bakowsky
    Abstract:

    Abstract Cytotoxicity is a major drawback impeding the therapeutic use of Gene delivery and Gene down-regulation vehicles. Apart from cytotoxicity, rapid degradation and low cellular uptake are other major factors affecting therapeutic use. Considering the above factors, formulation and development of PEI (Polyethylenimine) based, liposome encapsulated delivery vehicles with improved transfection efficiency and low cytotoxicity which can be used for Gene delivery and Gene Knockdown. DOPE (1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine), DPPC (Dipalmitoylphosphatidylcholine) and cholesterol have been considered as lipids of choice bearing in mind various factors such as rigidness and surface charge which greatly influence the formation of liposomes, polyplex encapsulation and transfection efficiency. For the condensation of plasmid DNA (pDNA) and short interfering RNA (siRNA), branched PEI 25 kDa (bPEI) and deacylated linear PEI 22 kDa (lPEI) were employed. lPEI and siRNA polyplexes encapsulated within DOPE/DPPC/Cholesterol (DDC) liposomes exhibited higher luc (luciferase) Gene Knockdown in vitro compared to the controls. They also showed superior transfection efficiencies compared to polyplexes in experiments using pCMV-luc (luciferase reporter plasmid) and pEGFP-N1 (Green Fluorescence protein reporter plasmid). This can partly be attributed to the improved integrity imparted by the liposomal layer which was confirmed by complex stability and integrity assays. Cytotoxicity and coagulation time assays of DDC-lPEI based lipopolyplexes showed decreased cytotoxic potential and negligible influence on coagulation respectively for compared to polyplexes, thus rendering them suitable for Gene therapy.

  • Composite liposome-PEI/nucleic acid lipopolyplexes for safe and efficient Gene delivery and Gene Knockdown
    Colloids and Surfaces B: Biointerfaces, 2017
    Co-Authors: Shashank Reddy Pinnapireddy, Lili Duse, Boris Strehlow, Jens Schafer, Udo Bakowsky
    Abstract:

    Abstract Cytotoxicity is a major drawback impeding the therapeutic use of Gene delivery and Gene down-regulation vehicles. Apart from cytotoxicity, rapid degradation and low cellular uptake are other major factors affecting therapeutic use. Considering the above factors, formulation and development of PEI (Polyethylenimine) based, liposome encapsulated delivery vehicles with improved transfection efficiency and low cytotoxicity which can be used for Gene delivery and Gene Knockdown. DOPE (1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine), DPPC (Dipalmitoylphosphatidylcholine) and cholesterol have been considered as lipids of choice bearing in mind various factors such as rigidness and surface charge which greatly influence the formation of liposomes, polyplex encapsulation and transfection efficiency. For the condensation of plasmid DNA (pDNA) and short interfering RNA (siRNA), branched PEI 25 kDa (bPEI) and deacylated linear PEI 22 kDa (lPEI) were employed. lPEI and siRNA polyplexes encapsulated within DOPE/DPPC/Cholesterol (DDC) liposomes exhibited higher luc (luciferase) Gene Knockdown in vitro compared to the controls. They also showed superior transfection efficiencies compared to polyplexes in experiments using pCMV-luc (luciferase reporter plasmid) and pEGFP-N1 (Green Fluorescence protein reporter plasmid). This can partly be attributed to the improved integrity imparted by the liposomal layer which was confirmed by complex stability and integrity assays. Cytotoxicity and coagulation time assays of DDC-lPEI based lipopolyplexes showed decreased cytotoxic potential and negligible influence on coagulation respectively for compared to polyplexes, thus rendering them suitable for Gene therapy.

Dennis Strand - One of the best experts on this subject based on the ideXlab platform.

  • sirna mediated in vivo Gene Knockdown by acid degradable cationic nanohydrogel particles
    Journal of Controlled Release, 2017
    Co-Authors: Nadine Leber, L Kaps, M Aslam, Jonathan Schupp, A Brose, David Schaffel, Karl Fischer, Mustafa Diken, Dennis Strand
    Abstract:

    Abstract Cationic nanohydrogel particles have become an attractive tool for systemic siRNA delivery, but improvement of their in vivo tolerance is desirable, especially to prevent potential long term side effects by tissue and cellular accumulation. Here, we designed novel ketal cross-linked cationic nanohydrogel particles that were assessed for reduced tissue accumulation and robust siRNA delivery in vitro and in vivo . An oligo-amine cross-linker equipped with a ketal moiety in its core was synthesized and applied to nanohydrogel cross-linking of self-assembled reactive ester block copolymers in DMSO. The resulting acid-sensitive cationic nanoparticles spontaneously disassembled over time in acidic milieu, as investigated by dynamic light scattering. Fluorescent correlation spectroscopy showed effective complexation with siRNA as well as its release upon particle degradation at endosomal pH. These properties resulted in an enhanced in vitro Gene Knockdown for the acid-degradable cationic nanoparticles compared to their non-degradable spermine analogues. In a murine liver fibrosis model enhanced carrier and payload accumulation in the fibrotic tissue facilitated sequence-specific Gene Knockdown and prevented fibrosis progression. Long-term monitoring of the carrier in the body showed an enhanced clearance for the acid-degradable carrier, even after multiple dosing. Therefore, these acid-degradable cationic nanohydrogel particles can be considered as promising siRNA carriers for in vivo purposes towards therapeutic applications.