The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform
Shlomo Margel - One of the best experts on this subject based on the ideXlab platform.
-
Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications.
Polymers, 2020Co-Authors: Elad Hadad, Igor Grinberg, Safra Rudnick-glick, Ella Itzhaki, Matan Y Avivi, Yuval Elias, Shlomo MargelAbstract:Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) Proteinoids and Proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy.
-
Designed Proteinoid polymers and nanoparticles encapsulating risperidone for enhanced antipsychotic activity
Journal of nanobiotechnology, 2020Co-Authors: L. Lugasi, Igor Grinberg, Safra Rudnick-glick, Haim Einat, E. Okun, Shlomo MargelAbstract:Nanoparticles (NPs) incorporating drug formulations can be used to facilitate passage through biological barriers including the blood–brain barrier (BBB) and increase drug delivery and bioavailability. Hence, NP-based administration may enhance the efficiency of current antipsychotics. Encapsulation within NPs can resolve aqueous solubility problems that not only reduce permeability through the BBB but also affect targeting. The present study describes a new drug delivery system based on Proteinoid NPs to explore the possibility of improving drug efficacy. Risperidone (RSP) is a commonly used atypical antipsychotic medication, and was therefore selected for encapsulation by Proteinoid NPs. Proteinoid polymers with high molecular weight and low polydispersity were synthesized from l-amino acids and poly-l-lactic acid (PLLA) by thermal step-growth polymerization mechanism. RSP-loaded Proteinoid NPs were then prepared using a self-assembly process in the presence of RSP, followed by PEGylation. The optimal PEGylated RSP-loaded NPs were characterized in terms of diameter and size distribution, drug loading, ζ-potential, cytotoxicity, biodistribution, and psychopharmacological effects. The findings indicate significantly higher antipsychotic activity of drug-loaded Proteinoid NPs compared to free RSP. Proteinoid NPs enhance RSP delivery and may potentially increase drug efficiency by reducing dosage and side effects.
-
Targeted Delivery of CBD-Loaded Poly (RGD) Proteinoid Nanoparticles for Antitumor Therapy
Journal of Nanomedicine & Nanotechnology, 2020Co-Authors: L. Lugasi, Igor Grinberg, Shlomo MargelAbstract:Background:Targeted nanoparticle (NP)-based drug delivery systems enable administration of non-soluble drugs and enhance their efficacy. The arginine-glycine-aspartic acid (RGD) motif is a known recognition site of integrins, and RGD receptors are overexpressed in tumors and their neovasculature and can be used as targets for tumor treatment. Cannabidiol (CBD), the main non-psychotropic phytocannabinoid of cannabis sativa, exhibits various therapeutic effects and has antitumor properties. Encapsulation of CBD within poly(RGD) (P(RGD)) Proteinoid NPs can overcome the poor solubility and bioavailability of CBD and target it to tumors in vivo. Methods: P(RGD) Proteinoid polymer was synthesized from D- and L-amino acids by thermal step-growth polymerization. CBD was encapsulated within the Proteinoid NPs by self-assembly process. CBD-loaded Proteinoid NPs were characterized in terms of particle diameter and size distribution, drug loading, ζ-potential, cytotoxicity, drug release, and biodistribution as well as antitumor effect. Results: P(RGD) Proteinoid polymer was obtained with high molecular weight and low polydispersity. CBD was successfully encapsulated in the Proteinoid NPs. The results demonstrated significant tumor growth inhibition by CBD-loaded P(RGD) Proteinoid NPs compared to free CBD solution. The targeted delivery of P(RGD) NPs to tumors in a xenograft mouse model significantly increases (p
-
Synthesis and Characterization of Poly(RGD) Proteinoid Polymers and NIR Fluorescent Nanoparticles of Optimal d,l-Configuration for Drug-Delivery Applications—In Vitro Study
ACS omega, 2020Co-Authors: Elad Hadad, Michal Kolitz-domb, Igor Grinberg, Safra Rudnick-glick, Jordan H. Chill, Shlomo MargelAbstract:RGD sequence is a tripeptide composed of three amino acids: arginine (R), glycine (G), and aspartic acid (D). The RGD peptide has a high affinity to the integrin alpha v beta 3, which is overexpressed on the membrane of many cancer cells and is attracted to areas of angiogenesis. Proteinoids are biodegradable polymers based on amino acids which are formed by bulk thermal step-growth polymerization mechanism. Hollow Proteinoid nanoparticles (NPs) may be formed via self-assembly process of the Proteinoid polymers. We propose using novel RGD-based Proteinoid polymers to manufacture NPs in which the RGD motif is self-incorporated in the Proteinoid backbone. Such P(RGD) NPs can act both as a drug carrier (by encapsulation of a desired drug) and as a targeting delivery system. This article presents the synthesis of four RGD Proteinoids with different RGD optical configurations, (d) or (l) arginine, glycine, and (d) or (l) aspartic acid, in order to determine which configuration is optimal as a drug-targeting carrier. These new RGD Proteinoid polymers possess high molecular weights and molecular weight monodispersity. Homonuclear nuclear magnetic resonance methods were employed to predict the expected concentration of RGD tripeptide sequence in the polymer. Near infrared fluorescent NPs have been prepared by the encapsulation of indocyanine green (ICG) dye within the different P(RGD) NPs. The dry diameters of the hollow P(RdGDd), P(RdGD), P(RGD), and P(RGDd) NPs are 55 ± 13, 48 ± 9, 45 ± 11, and 42 ± 9 nm, respectively, whereas those of the ICG-encapsulated NPs were significantly higher, 141 ± 24, 95 ± 13, 86 ± 11, and 87 ± 12 nm, respectively. The ICG-encapsulated P(RdGD) NPs exhibited higher selectivity toward epithelial injury, as demonstrated using an in vitro scratch assay, because the P(RdGD) NPs accumulated in the injured area at higher concentrations when compared to other P(RGD) NPs with different chiralities. Therefore, the P(RdGD) polymer configuration is the polymer of choice for use as a targeted drug carrier to areas of angiogenesis, such as in tumors, wounds, or cuts.
-
Proteinoid Nanocapsules as Drug Delivery System for Improving Antipsychotic Activity of Risperidone.
Molecules (Basel Switzerland), 2020Co-Authors: Liroy Lugasi, Igor Grinberg, Rivka Sabag, Ravit Madar, Haim Einat, Shlomo MargelAbstract:Risperidone (RSP) is an atypical antipsychotic drug widely used to treat schizophrenia and bipolar disorder. Nanoparticles (NPs) are being developed as in vivo targeted drug delivery systems, which cross the blood-brain barrier and improve pharmacokinetics and drug effectiveness. Here, biodegradable Proteinoids were synthesized by thermal step-growth polymerization from the amino acids l-glutamic acid, l-phenylalanine and l-histidine and poly (l-lactic acid). Proteinoid NPs containing RSP were then formed by self-assembly, overcoming the insolubility of the drug in water, followed by PEGylation (poly ethylene glycol (PEG) conjugation to increase the stability of the NPs in the aqueous continuous phase. These NPs are biodegradable owing to their peptide and ester moieties. They were characterized in terms of diameter, size distribution, drug loading, and long-term storage. Behavioral studies on mice found enhanced antipsychotic activity compared to free RSP.
Jinchul Kim - One of the best experts on this subject based on the ideXlab platform.
-
Monoolein cubic phase containing disulfide Proteinoid and its reduction-responsive release property
Journal of Dispersion Science and Technology, 2017Co-Authors: Kyeongnan Kwon, Jinchul KimAbstract:Monoolein (MO) cubic phase, which can release its payload in answering to reducing condition, was prepared by including a disulfide Proteinoid composed of Asp, DL-leucine (Leu), and dithiodipropion...
-
Emulsion stabilized with disulfide Proteinoid and its stability in reducing condition
Journal of Dispersion Science and Technology, 2017Co-Authors: Kyeongnan Kwon, Jinchul KimAbstract:Reduction-responsive oil-in-water emulsion was prepared by stabilizing droplets using a disulfide Proteinoid composed of Asp, Leu, and cystamine (Prot(ALC)). A disulfide-free Proteinoid (Prot(AL)) ...
-
Preparation of liposome bearing disulfide Proteinoid and its reduction-responsive release property.
Journal of biomaterials science. Polymer edition, 2017Co-Authors: Kyeongnan Kwon, Jinchul KimAbstract:Egg phosphatidylcholine (Egg PC) liposome bearing a disulfide Proteinoid exhibited a reduction-responsive release property. Proteinoid composed of Asp, Leu, and cystamine (Prot(ALC)) and Asp and Leu (Prot(AL)) were synthesized by thermal condensation, confirmed by Raman, FT-IR, 1H NMR and 13C NMR spectroscopy. Egg PC liposome bearing the Proteinoid was prepared by a film hydration and sonication method. The fluorescence quenching of dye (i.e. calcein) loaded in liposome bearing the Proteinoid was 68.1-78.1%. The mean hydrodynamic diameter of liposome bearing the Proteinoid was less than 200 nm and it decreased with increasing amount of the Proteinoid. On the TEM photo, multi-lamellar vesicles were observed and the vesicle diameter was 100-300 nm. At all the phospholipid to proteinod ratios tested (i.e. 1:0.01, 1:0.02, and 1:0.05 (w/w)), the release degree in 12 h of dye loaded in liposome bearing Prot(AL) was less than 2%, and it was almost the same regardless of dithiothreitol (DTT, a reducing agent) concentration (i.e. 0, 10, and 20 mM). Whereas the release degree of dye loaded in liposome bearing Prot(ALC) was 1.5-8.4% and it was significantly dependent on DTT concentration.
-
UV-triggerable alginate beads decorated with basic Proteinoid-coumarin conjugates.
Journal of biomaterials science. Polymer edition, 2014Co-Authors: Mi Kyoung Kang, Jinchul KimAbstract:UV-triggerable bead was prepared by coating the surface of alginate bead with a photo-responsive Proteinoid. Epoxypropoxy coumarin (EPC) was covalently attached to a basic Proteinoid composed of lysine and serine (PLS), and the PLS–EPC conjugate was used as a photo-responsive coat of the bead. EPC residues of PLS–EPC conjugate on the bead surface were photo-cross-linked upon the irradiation of λ = 365 nm, and then FITC-dextran was loaded as a fluorescence dye in the bead coated with photo-cross-linked PLS–EPC conjugate. Upon the irradiation of λ = 254 nm, the degree of release from the bead was enhanced possibly because the cross-linked network of PLS–EPC conjugate coating layer is photo-cleaved. The UV-triggerable bead developed in the present study could be applied to a UV-responsive drug carrier.
-
Light-sensitive liposomes containing coumarin-Proteinoid conjugate.
Journal of nanoscience and nanotechnology, 2012Co-Authors: Hee Jin Seo, Jinchul KimAbstract:Photo-sensitive liposomes were prepared by modifying the surface with coumarin derivative-Proteinoid conjugate. Epoxypropoxy coumarin (EPC) was conjugated to Proteinoid composed of Asp, Ser and Leu (PASL) using the reaction mixture of which EPC/PASL ratio was 8/1 (w/w). The molar ratio of Asp residue/Ser residue/Leu residue/EPC residue of the resulting conjugate was calculated to be 71.1:18.6/6.3/4.0 on 1H NMR spectrum. Egg phosphatidylcholine (egg PC) liposomes bearing PASL-EPC conjugate was prepared by hydrating egg PC dry film with a buffer solution containing the conjugate. Egg PC/PASL-EPC conjugate ratios (w/w) in the preparation were 100:1 to 100:20, and the specific loadings of EPC residue in the liposomes were 0.0002 mg/mg to 0.0018 mg/mg. The release from the liposomes prepared using the egg PC/PASL-EPC conjugate ratios of 100:5 began to markedly increase 30 min after the irradiation of lambda = 254 nm and the release degree in 180 min was about 30%. Without the UV irradiation, no appreciable release was observed.
Igor Grinberg - One of the best experts on this subject based on the ideXlab platform.
-
Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications.
Polymers, 2020Co-Authors: Elad Hadad, Igor Grinberg, Safra Rudnick-glick, Ella Itzhaki, Matan Y Avivi, Yuval Elias, Shlomo MargelAbstract:Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) Proteinoids and Proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy.
-
Designed Proteinoid polymers and nanoparticles encapsulating risperidone for enhanced antipsychotic activity
Journal of nanobiotechnology, 2020Co-Authors: L. Lugasi, Igor Grinberg, Safra Rudnick-glick, Haim Einat, E. Okun, Shlomo MargelAbstract:Nanoparticles (NPs) incorporating drug formulations can be used to facilitate passage through biological barriers including the blood–brain barrier (BBB) and increase drug delivery and bioavailability. Hence, NP-based administration may enhance the efficiency of current antipsychotics. Encapsulation within NPs can resolve aqueous solubility problems that not only reduce permeability through the BBB but also affect targeting. The present study describes a new drug delivery system based on Proteinoid NPs to explore the possibility of improving drug efficacy. Risperidone (RSP) is a commonly used atypical antipsychotic medication, and was therefore selected for encapsulation by Proteinoid NPs. Proteinoid polymers with high molecular weight and low polydispersity were synthesized from l-amino acids and poly-l-lactic acid (PLLA) by thermal step-growth polymerization mechanism. RSP-loaded Proteinoid NPs were then prepared using a self-assembly process in the presence of RSP, followed by PEGylation. The optimal PEGylated RSP-loaded NPs were characterized in terms of diameter and size distribution, drug loading, ζ-potential, cytotoxicity, biodistribution, and psychopharmacological effects. The findings indicate significantly higher antipsychotic activity of drug-loaded Proteinoid NPs compared to free RSP. Proteinoid NPs enhance RSP delivery and may potentially increase drug efficiency by reducing dosage and side effects.
-
Targeted Delivery of CBD-Loaded Poly (RGD) Proteinoid Nanoparticles for Antitumor Therapy
Journal of Nanomedicine & Nanotechnology, 2020Co-Authors: L. Lugasi, Igor Grinberg, Shlomo MargelAbstract:Background:Targeted nanoparticle (NP)-based drug delivery systems enable administration of non-soluble drugs and enhance their efficacy. The arginine-glycine-aspartic acid (RGD) motif is a known recognition site of integrins, and RGD receptors are overexpressed in tumors and their neovasculature and can be used as targets for tumor treatment. Cannabidiol (CBD), the main non-psychotropic phytocannabinoid of cannabis sativa, exhibits various therapeutic effects and has antitumor properties. Encapsulation of CBD within poly(RGD) (P(RGD)) Proteinoid NPs can overcome the poor solubility and bioavailability of CBD and target it to tumors in vivo. Methods: P(RGD) Proteinoid polymer was synthesized from D- and L-amino acids by thermal step-growth polymerization. CBD was encapsulated within the Proteinoid NPs by self-assembly process. CBD-loaded Proteinoid NPs were characterized in terms of particle diameter and size distribution, drug loading, ζ-potential, cytotoxicity, drug release, and biodistribution as well as antitumor effect. Results: P(RGD) Proteinoid polymer was obtained with high molecular weight and low polydispersity. CBD was successfully encapsulated in the Proteinoid NPs. The results demonstrated significant tumor growth inhibition by CBD-loaded P(RGD) Proteinoid NPs compared to free CBD solution. The targeted delivery of P(RGD) NPs to tumors in a xenograft mouse model significantly increases (p
-
Synthesis and Characterization of Poly(RGD) Proteinoid Polymers and NIR Fluorescent Nanoparticles of Optimal d,l-Configuration for Drug-Delivery Applications—In Vitro Study
ACS omega, 2020Co-Authors: Elad Hadad, Michal Kolitz-domb, Igor Grinberg, Safra Rudnick-glick, Jordan H. Chill, Shlomo MargelAbstract:RGD sequence is a tripeptide composed of three amino acids: arginine (R), glycine (G), and aspartic acid (D). The RGD peptide has a high affinity to the integrin alpha v beta 3, which is overexpressed on the membrane of many cancer cells and is attracted to areas of angiogenesis. Proteinoids are biodegradable polymers based on amino acids which are formed by bulk thermal step-growth polymerization mechanism. Hollow Proteinoid nanoparticles (NPs) may be formed via self-assembly process of the Proteinoid polymers. We propose using novel RGD-based Proteinoid polymers to manufacture NPs in which the RGD motif is self-incorporated in the Proteinoid backbone. Such P(RGD) NPs can act both as a drug carrier (by encapsulation of a desired drug) and as a targeting delivery system. This article presents the synthesis of four RGD Proteinoids with different RGD optical configurations, (d) or (l) arginine, glycine, and (d) or (l) aspartic acid, in order to determine which configuration is optimal as a drug-targeting carrier. These new RGD Proteinoid polymers possess high molecular weights and molecular weight monodispersity. Homonuclear nuclear magnetic resonance methods were employed to predict the expected concentration of RGD tripeptide sequence in the polymer. Near infrared fluorescent NPs have been prepared by the encapsulation of indocyanine green (ICG) dye within the different P(RGD) NPs. The dry diameters of the hollow P(RdGDd), P(RdGD), P(RGD), and P(RGDd) NPs are 55 ± 13, 48 ± 9, 45 ± 11, and 42 ± 9 nm, respectively, whereas those of the ICG-encapsulated NPs were significantly higher, 141 ± 24, 95 ± 13, 86 ± 11, and 87 ± 12 nm, respectively. The ICG-encapsulated P(RdGD) NPs exhibited higher selectivity toward epithelial injury, as demonstrated using an in vitro scratch assay, because the P(RdGD) NPs accumulated in the injured area at higher concentrations when compared to other P(RGD) NPs with different chiralities. Therefore, the P(RdGD) polymer configuration is the polymer of choice for use as a targeted drug carrier to areas of angiogenesis, such as in tumors, wounds, or cuts.
-
Proteinoid Nanocapsules as Drug Delivery System for Improving Antipsychotic Activity of Risperidone.
Molecules (Basel Switzerland), 2020Co-Authors: Liroy Lugasi, Igor Grinberg, Rivka Sabag, Ravit Madar, Haim Einat, Shlomo MargelAbstract:Risperidone (RSP) is an atypical antipsychotic drug widely used to treat schizophrenia and bipolar disorder. Nanoparticles (NPs) are being developed as in vivo targeted drug delivery systems, which cross the blood-brain barrier and improve pharmacokinetics and drug effectiveness. Here, biodegradable Proteinoids were synthesized by thermal step-growth polymerization from the amino acids l-glutamic acid, l-phenylalanine and l-histidine and poly (l-lactic acid). Proteinoid NPs containing RSP were then formed by self-assembly, overcoming the insolubility of the drug in water, followed by PEGylation (poly ethylene glycol (PEG) conjugation to increase the stability of the NPs in the aqueous continuous phase. These NPs are biodegradable owing to their peptide and ester moieties. They were characterized in terms of diameter, size distribution, drug loading, and long-term storage. Behavioral studies on mice found enhanced antipsychotic activity compared to free RSP.
Safra Rudnick-glick - One of the best experts on this subject based on the ideXlab platform.
-
Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications.
Polymers, 2020Co-Authors: Elad Hadad, Igor Grinberg, Safra Rudnick-glick, Ella Itzhaki, Matan Y Avivi, Yuval Elias, Shlomo MargelAbstract:Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) Proteinoids and Proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy.
-
Designed Proteinoid polymers and nanoparticles encapsulating risperidone for enhanced antipsychotic activity
Journal of nanobiotechnology, 2020Co-Authors: L. Lugasi, Igor Grinberg, Safra Rudnick-glick, Haim Einat, E. Okun, Shlomo MargelAbstract:Nanoparticles (NPs) incorporating drug formulations can be used to facilitate passage through biological barriers including the blood–brain barrier (BBB) and increase drug delivery and bioavailability. Hence, NP-based administration may enhance the efficiency of current antipsychotics. Encapsulation within NPs can resolve aqueous solubility problems that not only reduce permeability through the BBB but also affect targeting. The present study describes a new drug delivery system based on Proteinoid NPs to explore the possibility of improving drug efficacy. Risperidone (RSP) is a commonly used atypical antipsychotic medication, and was therefore selected for encapsulation by Proteinoid NPs. Proteinoid polymers with high molecular weight and low polydispersity were synthesized from l-amino acids and poly-l-lactic acid (PLLA) by thermal step-growth polymerization mechanism. RSP-loaded Proteinoid NPs were then prepared using a self-assembly process in the presence of RSP, followed by PEGylation. The optimal PEGylated RSP-loaded NPs were characterized in terms of diameter and size distribution, drug loading, ζ-potential, cytotoxicity, biodistribution, and psychopharmacological effects. The findings indicate significantly higher antipsychotic activity of drug-loaded Proteinoid NPs compared to free RSP. Proteinoid NPs enhance RSP delivery and may potentially increase drug efficiency by reducing dosage and side effects.
-
Synthesis and Characterization of Poly(RGD) Proteinoid Polymers and NIR Fluorescent Nanoparticles of Optimal d,l-Configuration for Drug-Delivery Applications—In Vitro Study
ACS omega, 2020Co-Authors: Elad Hadad, Michal Kolitz-domb, Igor Grinberg, Safra Rudnick-glick, Jordan H. Chill, Shlomo MargelAbstract:RGD sequence is a tripeptide composed of three amino acids: arginine (R), glycine (G), and aspartic acid (D). The RGD peptide has a high affinity to the integrin alpha v beta 3, which is overexpressed on the membrane of many cancer cells and is attracted to areas of angiogenesis. Proteinoids are biodegradable polymers based on amino acids which are formed by bulk thermal step-growth polymerization mechanism. Hollow Proteinoid nanoparticles (NPs) may be formed via self-assembly process of the Proteinoid polymers. We propose using novel RGD-based Proteinoid polymers to manufacture NPs in which the RGD motif is self-incorporated in the Proteinoid backbone. Such P(RGD) NPs can act both as a drug carrier (by encapsulation of a desired drug) and as a targeting delivery system. This article presents the synthesis of four RGD Proteinoids with different RGD optical configurations, (d) or (l) arginine, glycine, and (d) or (l) aspartic acid, in order to determine which configuration is optimal as a drug-targeting carrier. These new RGD Proteinoid polymers possess high molecular weights and molecular weight monodispersity. Homonuclear nuclear magnetic resonance methods were employed to predict the expected concentration of RGD tripeptide sequence in the polymer. Near infrared fluorescent NPs have been prepared by the encapsulation of indocyanine green (ICG) dye within the different P(RGD) NPs. The dry diameters of the hollow P(RdGDd), P(RdGD), P(RGD), and P(RGDd) NPs are 55 ± 13, 48 ± 9, 45 ± 11, and 42 ± 9 nm, respectively, whereas those of the ICG-encapsulated NPs were significantly higher, 141 ± 24, 95 ± 13, 86 ± 11, and 87 ± 12 nm, respectively. The ICG-encapsulated P(RdGD) NPs exhibited higher selectivity toward epithelial injury, as demonstrated using an in vitro scratch assay, because the P(RdGD) NPs accumulated in the injured area at higher concentrations when compared to other P(RGD) NPs with different chiralities. Therefore, the P(RdGD) polymer configuration is the polymer of choice for use as a targeted drug carrier to areas of angiogenesis, such as in tumors, wounds, or cuts.
-
Engineering of NIR fluorescent PEGylated poly(RGD) Proteinoid polymers and nanoparticles for drug delivery applications in chicken embryo and mouse models
RSC Advances, 2020Co-Authors: Elad Hadad, Igor Grinberg, Safra Rudnick-glick, Ronen Yehuda, Shlomo MargelAbstract:Proteinoids are non-toxic biodegradable polymers based on thermal step-growth polymerization of natural or synthetic amino acids. Hollow Proteinoid nanoparticles (NPs) may then be formed via a self-assembly process of the Proteinoid polymers in an aqueous solution. In the present article polymers and NPs based on D-arginine, glycine and L-aspartic acid, poly(RDGD), were synthesized for tumor targeting, particularly due to the high affinity of the RGD motif to areas of angiogenesis. Near IR fluorescent P(RDGD) NPs were prepared by encapsulating the fluorescent NIR dye indocyanine green (ICG) within the formed P(RDGD) NPs. Here, we investigate the effect of the covalent conjugation of polyethylene glycol (PEG), with different molecular weights, to the surface of the near IR encapsulated P(RDGD) NPs on the release of the dye to human serum due to bio-degradation of the Proteinoid NPs and on the uptake by tumors. This work illustrates that the release of the encapsulated ICG from the non-PEGylated NPs is significantly faster than for that observed for the PEGylated NPs, and that the higher molecular weight is the bound PEG spacer the slower is the dye release profile. In addition, in a chicken embryo model, the non-PEGylated ICG-encapsulated P(RDGD) NPs exhibited a higher uptake in the tumor region in comparison to the PEGylated ICG-encapsulated P(RDGD) NPs. However, in a tumor xenograft mouse model, which enables a prolonged experiment, the importance of the PEG is clearly noticeable, when a high concentration of PEGylated P(RDGD) NPs was accumulated in the area of the tumor compared to the non-PEGylated P(RDGD). Moreover, the length of the PEG chain plays a major role in the ability to target the tumor. Hence, we can conclude that selectivity towards the tumor area of non-PEGylated and the PEGylated ICG-encapsulated P(RDGD) NPs can be utilized for targeting to areas of angiogenesis, such as in the cases of tumors, wounds or cuts, etc.
K. Panduranga Rao - One of the best experts on this subject based on the ideXlab platform.
-
Preparation and characterization of pH-sensitive Proteinoid microspheres for the oral delivery of methotrexate
Biomaterials, 1998Co-Authors: A.b. Madhan Kumar, K. Panduranga RaoAbstract:Prot A7, a polypeptidic Proteinoid composed of seven different amino acids, was synthesized and microspheres of 1-5 microm size were prepared by the self-assembly process. The morphological characterization of the microspheres was carried out using optical microscopy and SEM (scanning electron microscopy). Emphasis also has been made on studying the mechanism behind the microsphere formation and to relate it with the conformation of the polypeptide. These self-assembled microspheres were found to be pH-sensitive in aqueous medium. The suitability of the Prot A7 microspheres as a carrier for gastric irritant drugs was verified by choosing methotrexate (MTX) as a model drug. MTX was entrapped in Proteinoid microspheres and its utility for the oral delivery system was verified by carrying out the drug dissolution studies in simulated gastric medium (pH 1.2) and neutral medium of the blood (pH 7) under physiological conditions. The pH responsive dissolution behaviour of the microspheres was clarified.
-
Synthesis and aggregational behavior of acidic Proteinoid
Journal of Polymer Science Part A: Polymer Chemistry, 1996Co-Authors: A.b. Madhan Kumar, Rangasamy Jayakumar, K. Panduranga RaoAbstract:Polypeptide-based acidic Proteinoid containing L-glutamic acid and L-aspartic acid in excess and five other neutral and basic amino acids in minor proportions have been synthesized and found that it forms organized aggregates in an aqueous solution. The Proteinoid aggregate has been characterized using 13 C-NMR, IR, and fluorescence spectroscopic techniques. The c.m.c. of the Proteinoid has been determined by conductometric and pH metric methods. The aggregation studies were carried out at different temperatures and varying ionic strengths of the medium. The phase transition of the Proteinoid aggregate has been determined using the fluorescence absorbance method. The aggregation behavior is shown to be dependent on the pH of the solution. This was also supported by conductivity measurements. Using methylene blue as a model drug, the drug delivery property of the Proteinoid micelles were studied in acidic (pH 4.5) and neutral (pH 7.4) mediums. Using biphasic model thermochemical parameters, ΔG, ΔH, ΔS, and ΔC p have been evaluated.
