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Treatment of acute lung inflammation by pulmonary delivery of anti-TNF- α siRNA with PAMAM dendrimers in a murine model.
In this study, commercially available generation 3 poly(amidoamine) (PAMAM) dendrimer was investigated for pulmonary delivery of siRNA directed against tumor necrosis factor (TNF) α for the treatment of acute lung inflammation. Delivery efficiency was assessed in vitro in the RAW264.7 macrophage cell line activated with lipopolysaccharide (LPS), and efficacy was evaluated in vivo in a murine model of LPS-induced lung inflammation upon pre-treatment with TNF-α siRNA. The PAMAM dendrimer-siRNA complexes (dendriplexes) displayed strong siRNA condensation and high cellular uptake in macrophages compared with non-complexed si...
Source: European Journal of Pharmaceutics and Biopharmaceutics - August 12, 2020 Category: Drugs & Pharmacology Authors: Bohr A, Tsapis N, Foged C, Andreana I, Yang M, Fattal E Tags: Eur J Pharm Biopharm Source Type: research

Study of Double-Targeting Nanoparticles Loaded With MCL-1 siRNA and Dexamethasone for Adjuvant-induced Arthritis Therapy.
In this study, HA-coated pH-responsive nanoparticles loaded with MCL-1 small interfering RNA (siRNA) and dexamethasone (HNPs/MD) were developed for RA treatment. The HNPs/MD had a mean particle size of 117.07 ± 2.21 nm and zeta potential of 15.53 ± 1.06 mV. The release rates of both MCL-1 siRNA and dexamethasone from the HNPs/MD at pH 4.5 and 6.0 were higher than those at pH 7.4, indicating that the nanoparticles were acid-sensitive. Cytotoxicity assays showed that compared with single drug loaded nanoparticles, the HNPs/MD showed higher cytotoxicity to activated macrophages. The superior therapeutic effect of HNPs/MD wa...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 14, 2020 Category: Drugs & Pharmacology Authors: Li X, Yu C, Meng X, Hou Y, Cui Y, Zhu T, Li Y, Teng L, Sun F, Li Y Tags: Eur J Pharm Biopharm Source Type: research

Charge reversible hyaluronic acid-modified dendrimer-based nanoparticles for siMDR-1 and doxorubicin co-delivery.
In this study, generation 4 polyamodoamine (PAMAM) was conjugated with PEG2k-DOPE. The PAMAM-PEG2k-DOPE co-polymer, together with mPEG2k-DOPE, was formulated into mixed dendrimer micelles (MDMs) that can complex siRNA through the cationic PAMAM moieties and encapsulate hydrophobic drug in the micellar lipid cores. DOPE-conjugated hyaluronic acid (HA) was coated on the surface of MDMs to shield the exposed positive charge on PAMAM and to increase the cellular association with CD44+ cancer cells. The HA-modified MDMs could form stable complexes with siRNA, prevent RNase-mediated siRNA degradation and maintain its integrity. ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 5, 2020 Category: Drugs & Pharmacology Authors: Zhang X, Pan J, Yao M, Palmerston Mendes L, Sarisozen C, Mao S, Torchilin VP Tags: Eur J Pharm Biopharm Source Type: research

Corrigendum to "Polyethylenimine nanoparticles as an efficient in vitro siRNA delivery system" Eur. J. Pharm. Biopharm. 73 (2009) 43-49.
PMID: 31470968 [PubMed - in process]
Source: European Journal of Pharmaceutics and Biopharmaceutics - August 31, 2019 Category: Drugs & Pharmacology Authors: Nimesh S, Chandra R Tags: Eur J Pharm Biopharm Source Type: research

Lipidoid-Polymer Hybrid Nanoparticles Loaded with TNF siRNA Suppress Inflammation after Intra-articular Administration in a Murine Experimental Arthritis Model.
Abstract Rheumatoid arthritis (RA) is a common autoimmune disease, which is characterized by painful chronic inflammation in the joints, and novel safe and efficacious treatments are urgently needed. RNA interference (RNAi) therapy based on small interfering RNA (siRNA) is a promising approach for silencing specific genes involved in inflammation. However, delivery of siRNA to the target site, i.e. the cytosol of immune cells, is a challenge. Here, we designed lipid-polymer hybrid nanoparticles (LPNs) composed of lipidoid and poly(DL-lactic-co-glycolic acid) loaded with a therapeutic cargo siRNA directed against t...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 10, 2019 Category: Drugs & Pharmacology Authors: Jansen MAA, Klausen LH, Thanki K, Lyngsø J, Skov Pedersen J, Franzyk H, Nielsen HM, van Eden W, Dong M, Broere F, Foged C, Zeng X Tags: Eur J Pharm Biopharm Source Type: research

Anisamide-targeted PEGylated gold nanoparticles designed to target prostate cancer mediate: Enhanced systemic exposure of siRNA, tumour growth suppression and a synergistic therapeutic response in combination with paclitaxel in mice.
In this study, AuNPs capped with polyethylenimine (PEI) and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of positively charged anisamide-targeted PEGylated AuNPs (namely Au-PEI-PEG-AA). The anisamide-targeted AuNPs effectively complexed siRNA via electrostatic interaction, and the resultant complex (Au110-PEI-PEG5000-AA.siRNA) illustrated favourable physicochemical characteristics, including particle size, surface charge, and stability. In vitro, anisamide-targeted AuNPs selectively bound to human prostate cancer PC-3 cells, inducing efficient endosomal escape of ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - February 16, 2019 Category: Drugs & Pharmacology Authors: Luan X, Rahme K, Cong Z, Wang L, Zou Y, He Y, Yang H, Holmes JD, O'Driscoll CM, Guo J Tags: Eur J Pharm Biopharm Source Type: research

Polyamidoamine dendrimers-based nanomedicine for combination therapy with siRNA and chemotherapeutics to overcome multidrug resistance.
Abstract Multidrug resistance (MDR) significantly decreases the therapeutic efficiency of anti-cancer drugs. Its reversal could serve as a potential method to restore the chemotherapeutic efficiency. Downregulation of MDR-related proteins with a small interfering RNA (siRNA) is a promising way to reverse the MDR effect. Additionally, delivery of small molecule therapeutics simultaneously with siRNA can enhance the efficiency of chemotherapy by dual action in MDR cell lines. Here, we conjugated the dendrimer, generation 4 polyamidoamine (G4 PAMAM), with a polyethylene glycol (PEG)-phospholipid copolymer. The amphip...
Source: European Journal of Pharmaceutics and Biopharmaceutics - January 8, 2019 Category: Drugs & Pharmacology Authors: Pan J, Palmerston Mendes L, Yao M, Filipczak N, Garai S, Thakur GA, Sarisozen C, Torchilin VP Tags: Eur J Pharm Biopharm Source Type: research

Lipodendriplexes: A promising nanocarrier for enhanced gene delivery with minimal cytotoxicity.
In this study, we developed an advanced variant of the dendriplexes by encapsulating them within liposomes to enhance their gene delivery efficiency. This liposome encapsulated dendriplex system can further reduce unwanted cytotoxicity and enhance cellular uptake of nucleic acids. A broad range of lipid combinations were used to optimize the lipodendriplexes in terms of their physicochemical characteristics including size, shape and zeta potential. The optimized lipodendriplexes were tested for pDNA transfection, in vitro cell viability, cellular uptake, siRNA mediated knockdown, hemocompatibility, metastatic progression a...
Source: European Journal of Pharmaceutics and Biopharmaceutics - December 24, 2018 Category: Drugs & Pharmacology Authors: Tariq I, Reddy Pinnapireddy S, Duse L, Yasir Ali M, Ali S, Umair Amin M, Goergen N, Jedelská J, Schäfer J, Bakowsky U Tags: Eur J Pharm Biopharm Source Type: research

siRNA-mediated protein knockdown in precision-cut lung slices.
Abstract Small interfering RNA (siRNA) can induce RNA interference, which leads to the knockdown of messenger RNA (mRNA) and protein. As a result, siRNA is often used in vitro and in vivo to unravel the function of genes and as a therapeutic agent to disrupt excessive expression of disease-related genes. However, there is a large gap between in vitro and in vivo models in terms of simplicity, flexibility, throughput, and translatability. This gap could be bridged by using precision-cut tissue slices, which represent viable explants prepared from animal or human tissue that can be cultured ex vivo. Previously, we d...
Source: European Journal of Pharmaceutics and Biopharmaceutics - November 7, 2018 Category: Drugs & Pharmacology Authors: Ruigrok MJR, Xian JL, Frijlink HW, Melgert BN, Hinrichs WLJ, Olinga P Tags: Eur J Pharm Biopharm Source Type: research

Formulation and in vitro evaluation of a siRNA delivery nanosystem decorated with gH625 peptide for triple negative breast cancer theranosis.
Abstract The development of an efficient small interfering RNA (siRNA) delivery system has held scientists interest since the discovery of the RNA interference mechanism (RNAi). This strategy gives hope for the treatment of many severe diseases. Herein, we developed hybrid nanovectors able to deliver siRNA to triple negative breast cancer cells. The nanovectors are based on PEGylated superparamagnetic iron oxide nanoparticles (SPION) functionalized with gH625 peptide, chitosan and poly-L-arginine. Every component has a key role and specific function: SPION is the core scaffolding the nanovector; PEG participates i...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 28, 2018 Category: Drugs & Pharmacology Authors: Ben Djemaa S, David S, Hervé-Aubert K, Falanga A, Galdiero S, Allard-Vannier E, Chourpa I, Munnier E Tags: Eur J Pharm Biopharm Source Type: research

siRNA/Lipopolymer Nanoparticles to Arrest Growth of Chronic Myeloid Leukemia Cells In Vitro and In Vivo.
Abstract Therapies for the treatment of Chronic Myeloid Leukemia and other leukemias are still limited for patients at advanced stages, which allow development of point mutations in the BCR-ABL fusion gene that render CML cells insensitive to therapies. An effective non-viral delivery system based on lipopolymers is described in this study to deliver specific siRNAs to CML cells for therapeutic gene silencing. The lipopolymer, based on the lipid α-linolenic acid (αLA) substitution on low molecular weight polyethyleneimine (PEI), was used to deliver siRNA against the BCR-ABL gene and, the resultant therapeutic ef...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 15, 2018 Category: Drugs & Pharmacology Authors: Valencia-Serna J, Aliabadi HM, Manfrin A, Mohseni M, Jiang X, Uludag H Tags: Eur J Pharm Biopharm Source Type: research

Targeted delivery of nucleic acids into xenograft tumors mediated by novel folate-equipped liposomes.
Abstract Folate receptors (FR) are cellular markers highly expressed in various cancer cells. Here, we report on the synthesis of a novel folate-containing lipoconjugate (FC) built of 1,2-di-O-ditetradecyl-rac-glycerol and folic acid connected via a PEG spacer, and the evaluation of the FC as a targeting component of liposomal formulations for nucleic acid (NA) delivery into FR expressing tumor cells. FR-targeting liposomes, based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosan tetrahydrochloride (2X3), lipid helper dioleoylphosphatidylethanolamine (DOPE) and novel ...
Source: European Journal of Pharmaceutics and Biopharmaceutics - November 18, 2017 Category: Drugs & Pharmacology Authors: Kabilova TO, Shmendel EV, Gladkikh DV, Chernolovskaya EL, Markov OV, Morozova NG, Maslov MA, Zenkova MA Tags: Eur J Pharm Biopharm Source Type: research

Folate appended cyclodextrins for drug, DNA, and siRNA delivery.
Abstract Drug, DNA, and siRNA delivery systems based on cyclodextrin (CD) core and connected with folate (FA) via various linkers are presented. They include simple mono-derivatized cyclodextrins as well as cyclodextrins with higher degree of substitution, both in their primary and secondary sides. Examples of simple polymers and dendrimers are also discussed. Such carriers possess properties inherent to both of their components. Cyclodextrin provides the ability to encapsulate organic molecules in its inner cavity, thus improving their solubility in water, bioavailability, and stability, while FA assures targetin...
Source: European Journal of Pharmaceutics and Biopharmaceutics - September 9, 2017 Category: Drugs & Pharmacology Authors: Ceborska M Tags: Eur J Pharm Biopharm Source Type: research

Inhalable siRNA-loaded nano-embedded microparticles engineered using microfluidics and spray drying.
This study demonstrates that inexpensive and scalable micromixers can be used to optimize the production of siRNA-dendrimer nanocomplexes, and they can be applied in combination with spray drying for the engineering of dry powder formulations suitable for delivery of siRNA to the therapeutic target site. PMID: 28780275 [PubMed - as supplied by publisher]
Source: European Journal of Pharmaceutics and Biopharmaceutics - August 2, 2017 Category: Drugs & Pharmacology Authors: Agnoletti M, Bohr A, Thanki K, Wan F, Zeng X, Peter Boetker J, Yang M, Foged C Tags: Eur J Pharm Biopharm Source Type: research

Engineering of small interfering RNA-loaded lipidoid-poly(DL-Lactic-Co-Glycolic Acid) hybrid nanoparticles for highly efficient and safe gene silencing: A quality by design-based approach.
Abstract Safety and efficacy of therapeutics based on RNA interference, e.g., small interfering RNA (siRNA), are dependent on the optimal engineering of the delivery technology, which is used for intracellular delivery of siRNA to the cytosol of target cells. We investigated the hypothesis that commonly used and poorly tolerated cationic lipids might be replaced with more efficacious and safe lipidoids as the lipid component of siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) for achieving more efficient gene silencing at lower and safer doses. However, formulation design of such a complex formulation is hig...
Source: European Journal of Pharmaceutics and Biopharmaceutics - July 26, 2017 Category: Drugs & Pharmacology Authors: Thanki K, Zeng X, Justesen S, Tejlmann S, Falkenberg E, Van Driessche E, Mørck Nielsen H, Franzyk H, Foged C Tags: Eur J Pharm Biopharm Source Type: research

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