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Source: Biomacromolecules

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Total 92 results found since Jan 2013.

siRNA delivery with chitosan: influence of chitosan molecular weight, degree of deacetylation and amine to phosphate ratio on in vitro silencing efficiency, hemocompatibility, biodistribution and in vivo efficacy.
Abstract Chitosan (CS) shows in vitro and in vivo efficacy for siRNA delivery, but with contradictory findings for incompletely characterized systems. To understand which parameters produce effective delivery, a library of precisely characterized chitosans was produced at different DDAs and Mn. Encapsulation and transfection efficiencies were characterized in vitro. Formulations were selected to examine the influence of Mn and N:P ratio on nanoparticle uptake, metabolic activity, genotoxicity, and in vitro transfection. Hemocompatibility and in vivo biodistribution were then investigated for different Mn, N:P rati...
Source: Biomacromolecules - December 6, 2017 Category: Biochemistry Authors: Alameh MG, Lavertu M, Tran-Khanh N, Chang CY, Lesage F, Bail M, Darras V, Chevrier A, Buschmann MD Tags: Biomacromolecules Source Type: research

Well-defined cationic N-3-(dimethylamino)propylmethacrylamide hydrochloride based (co)polymers for siRNA delivery.
Abstract Cationic glycopolymers have shown to be excellent candidates for the fabrication of gene delivery devices due to their ability to electrostatically interact with negatively charged nucleic acids and the carbohydrate residues ensure enhanced stability and low toxicity of the polyplexes. The ability to engineer the polymers for optimized compositions, molecular weights and architectures is critical in the design of effective gene delivery vehicles. Therefore, in this study, the aqueous reversible addition-fragmentation chain transfer polymerization (RAFT) was used to synthesize well-defined cationic glycopo...
Source: Biomacromolecules - December 1, 2017 Category: Biochemistry Authors: Singhsa P, Diaz-Dussan D, Manuspiya H, Narain R Tags: Biomacromolecules Source Type: research

Synthesis and in vitro evaluation of monodisperse amino-functional polyester dendrimers with rapid degradability and antibacterial properties.
Abstract Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as anti-viral agents. In this work, hydroxyl functional dendrimers o...
Source: Biomacromolecules - November 13, 2017 Category: Biochemistry Authors: Stenström P, Hjort E, Zhang Y, Andrén OCJ, Guette-Marquet S, Schultzberg M, Malkoch M Tags: Biomacromolecules Source Type: research

Self-assembled Polypeptide Nanogels with Enzymatically Transformable Surface as an siRNA Delivery Platform.
Abstract Nanometer-size gel particles, or nanogels, have potential for delivering therapeutic macromolecules. A cationic surface promotes cellular internalization of nanogels but undesired electrostatic interactions, such as with blood components, cause instability and toxicities. Polyethylene glycol coating has been used to shield charges, but this decreases delivery efficiency. Technical difficulties in synthesis and controlling molecular weights make it unfeasible to, instead, coat with biodegradable polymers. Our proposed solution is cationized nanogels enzymatically functionalized with branched polysaccharide...
Source: Biomacromolecules - October 23, 2017 Category: Biochemistry Authors: Nishimura T, Yamada A, Umezaki K, Sawada SI, Mukai SA, Sasaki Y, Akiyoshi K Tags: Biomacromolecules Source Type: research

Glycosylated RAFT polymers with varying PEG linkers produce different siRNA uptake, gene silencing and toxicity profiles.
Abstract Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape and efficient cargo release. These challenges have resulted in a significant body of research, and led to many important findings about the chemical composition and structural layout of t...
Source: Biomacromolecules - October 23, 2017 Category: Biochemistry Authors: Williams EGL, Hutt OE, Hinton TM, Larnaudie SC, Le T, MacDonald JM, Gunatillake P, Thang SH, Duggan PJ Tags: Biomacromolecules Source Type: research

Diblock copolymer hydrophobicity facilitates efficient gene silencing and cytocompatible nanoparticle-mediated siRNA delivery to musculoskeletal cell types.
Abstract pH-responsive diblock copolymers provide tailorable nanoparticle (NP) architecture and chemistry critical for siRNA delivery. Here, diblock polymers varying in first (corona) and second (core) block molecular weight (Mn), Corona:Core ratio and core hydrophobicity (%BMA) were synthesized to determine their effect on siRNA delivery in murine tenocytes (mTenocyte) and murine and human mesenchymal stem cells (mMSC and hMSCs, respectively). NP-mediated siRNA uptake, gene silencing, and cytocompatibility were quantified. Uptake is positively correlated with first block Mn in mTenocytes and hMSCs (p≤0.0005). A...
Source: Biomacromolecules - September 29, 2017 Category: Biochemistry Authors: Malcolm DW, Freeberg MAT, Wang Y, Sims KR, Awad HA, Benoit DSW Tags: Biomacromolecules Source Type: research

A Combination of Guanidyl and Phenyl Groups on Dendrimer Enables Efficient siRNA and DNA Delivery.
This study provides a new strategy to develop multifunctional polymers for efficient siRNA and DNA delivery. PMID: 28686016 [PubMed - as supplied by publisher]
Source: Biomacromolecules - July 7, 2017 Category: Biochemistry Authors: Chang H, Zhang J, Wang H, Lv J, Cheng Y Tags: Biomacromolecules Source Type: research

Efficient dual siRNA and drug delivery using engineered lipoproteoplexes.
Abstract An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favor...
Source: Biomacromolecules - July 7, 2017 Category: Biochemistry Authors: Liu CF, Chen R, Frezzo JA, Katyal P, Hill LK, Yin L, Srivastava N, More HT, Renfrew PD, Bonneau R, Montclare JK Tags: Biomacromolecules Source Type: research

Efficient receptor mediated siRNA delivery in vitro by folic acid targeted pentablock copolymer-based micelleplexes.
Abstract Novel, biocompatible polyplexes, based on the combination of cationic pentablock copolymers with folic acid functionalized copolymers were designed and developed for target-specific siRNA delivery. The resulting micelleplexes spontaneously formed polymeric micelles with a hydrophobic core surrounded directly by a cationic poly-2-(4-azidobutyl)-oxazole (PABOXA) and subsequently shielded by hydrophilic poly-2-methyl-oxazole (PMOXA) layer. The described micelleplexes form highly stable particles even in complete serum after 24 h compared with the highly cationic polymer PEI, which show aggregate formation in...
Source: Biomacromolecules - July 4, 2017 Category: Biochemistry Authors: Lehner R, Liu K, Wang X, Hunziker P Tags: Biomacromolecules Source Type: research

Anti-inflammatory effect of anti-tnf- α cationic phosphorous dendrimers nanocomplexes administered intranasally in a murine acute lung injury model.
ANTI-INFLAMMATORY EFFECT OF ANTI-TNF-α CATIONIC PHOSPHOROUS DENDRIMERS NANOCOMPLEXES ADMINISTERED INTRANASALLY IN A MURINE ACUTE LUNG INJURY MODEL. Biomacromolecules. 2017 Jun 22;: Authors: Bohr A, Tsapis N, Andreana I, Chamarat A, Foged C, Delomenie C, Noiray M, El Brahmi N, Majoral JP, Mignani S, Fattal E Abstract Inflammation is an essential component of many lung diseases, including asthma, chronic obstructive pulmonary disease (COPD) or acute lung injury. Our purpose was to design efficient carriers for lung delivery of small interfering RNA (siRNA) targeting tumor necrosis factor (TNF-α) in an...
Source: Biomacromolecules - June 22, 2017 Category: Biochemistry Authors: Bohr A, Tsapis N, Andreana I, Chamarat A, Foged C, Delomenie C, Noiray M, El Brahmi N, Majoral JP, Mignani S, Fattal E Tags: Biomacromolecules Source Type: research

Anionic polymer and quantum dot excipients to facilitate siRNA release and self-reporting of disassembly in stimuli-responsive nanocarrier formulations.
Abstract The incorporation of anionic excipients into polyplexes is a promising strategy for modulating siRNA binding vs. release and integrating diagnostic capabilities; however, specific design criteria and structure-function relationships are needed to facilitate the development of nanocarrier-based theranostics. Herein, we incorporated poly(acrylic acid) (PAA) and quantum dot (QD) excipients into photolabile siRNA polyplexes to increase gene silencing efficiencies by up to 100% and enable self-reporting of nanocarrier disassembly. Our systematic approach identified the functional relationships between gene sil...
Source: Biomacromolecules - April 25, 2017 Category: Biochemistry Authors: Greco CT, Andrechak JC, Epps Iii TH, Sullivan MO Tags: Biomacromolecules Source Type: research

Injectable, Guest-Host Assembled Polyethylenimine Hydrogel for siRNA Delivery.
Abstract While siRNA has tremendous potential for therapeutic applications, advancement is limited by poor delivery systems. Systemically, siRNAs are rapidly degraded, may have off-target silencing, and necessitate high working concentrations. To overcome this, we developed an injectable, guest-host assembled hydrogel between polyethylenimine (PEI) and polyethylene glycol (PEG) for local siRNA delivery. Guest-host modified polymers assembled with siRNAs to form polyplexes that had improved transfection and viability compared to PEI. At higher concentrations, these polymers assembled into shear-thinning hydrogels t...
Source: Biomacromolecules - December 19, 2016 Category: Biochemistry Authors: Wang LL, Sloand JN, Gaffey AC, Venkataraman CM, Wang Z, Trubelja A, Hammer DA, Atluri P, Burdick JA Tags: Biomacromolecules Source Type: research

Comparing gene silencing and physiochemical properties in siRNA bound cationic star-polymer complexes.
Abstract The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle t...
Source: Biomacromolecules - October 5, 2016 Category: Biochemistry Authors: Dearnley M, Reynolds NP, Cass P, Wei X, Shi S, Mohammed AA, Le T, Gunatillake P, Tizard ML, Thang SH, Hinton TM Tags: Biomacromolecules Source Type: research

Michael Addition Polymerization of Trifunctional Amine and Acrylic Monomer: A Versatile Platform for Development of Biomaterials.
Abstract Michael addition polymerizations of amines and acrylic monomers are versatile approaches to biomaterials for various applications. A combinatorial library of poly(β-amino ester)s and diverse poly(amido amine)s from diamines and diacrylates or bisacrylamides have been reported, respectively. Furthermore novel linear and hyperbranched polymers from Michael addition polymerizations of trifunctional amines and acrylic monomers significantly enrich this category of biomaterials. In this Review, we focus on the biomaterials from Michael addition polymerizations of trifunctional amines and acrylic monomers. Fir...
Source: Biomacromolecules - September 5, 2016 Category: Biochemistry Authors: Cheng W, Wu DC, Liu Y Tags: Biomacromolecules Source Type: research

Mapping Optimal Charge Density and Length of ROMP-based PTDMs for siRNA Internalization.
Abstract A fundamental understanding of how polymer structure impacts internalization and delivery abilities of biologically relevant cargoes, particularly siRNA, is of critical importance to the successful design of improved delivery reagents. Herein we report the use of ring-opening metathesis polymerization (ROMP) methods to synthesize two series of guanidinium-rich protein transduction domain mimics (PTDMs): one based on an imide scaffold that contains one guanidinium moiety per repeat unit and another based on a diester scaffold that contains two guanidinium moieties per repeat unit. By varying both the degre...
Source: Biomacromolecules - September 5, 2016 Category: Biochemistry Authors: Caffrey LM, deRonde BM, Minter LM, Tew GN Tags: Biomacromolecules Source Type: research