Abstract:
:While polymeric nano-formulations for RNAi therapeutics hold great promise for molecularly-targeted, personalized medicine, they possess significant systemic delivery challenges including rapid clearance from circulation and the potential for carrier-associated toxicity due to cationic polymer or lipid components. Herein, we evaluated the in vivo pharmacokinetic and safety impact of often-overlooked formulation parameters, including the ratio of carrier polymer to cargo siRNA and hydrophobic siRNA modification in combination with hydrophobic polymer components (dual hydrophobization). For these studies, we used nano-polyplexes (NPs) with well-shielded, zwitterionic coronas, resulting in various NP formulations of equivalent hydrodynamic size and neutral surface charge regardless of charge ratio. Doubling nano-polyplex charge ratio from 10 to 20 increased circulation half-life five-fold and pharmacokinetic area under the curve four-fold, but was also associated with increased liver enzymes, a marker of hepatic damage. Dual hydrophobization achieved by formulating NPs with palmitic acid-modified siRNA (siPA-NPs) both reduced the amount of carrier polymer required to achieve optimal pharmacokinetic profiles and abrogated liver toxicities. We also show that optimized zwitterionic siPA-NPs are well-tolerated upon long-term, repeated administration in mice and exhibit greater than two-fold increased uptake in orthotopic MDA-MB-231 xenografts compared to commercial transfection reagent, in vivo-jetPEI®. These data suggest that charge ratio optimization has important in vivo implications and that dual hydrophobization strategies can be used to maximize both NP circulation time and safety.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Jackson MA,Bedingfield SK,Yu F,Stokan ME,Miles RE,Curvino EJ,Hoogenboezem EN,Bonami RH,Patel SS,Kendall PL,Giorgio TD,Duvall CLdoi
10.1016/j.biomaterials.2018.11.010subject
Has Abstractpub_date
2019-02-01 00:00:00pages
245-259eissn
0142-9612issn
1878-5905pii
S0142-9612(18)30787-7journal_volume
192pub_type
杂志文章相关文献
BIOMATERIALS文献大全abstract::Plaque-induced lesions can produce peri-implant bone loss with ultimate implant loss. Although the peri-implant tissues seem to be more resistant than the periodontal ones to plaque and calculus, they can produce a more extensive spread of the infection to the deeper tissues around implants. The case of a 45-year-old ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(95)93116-u
更新日期:1995-08-01 00:00:00
abstract::It is estimated that 4 to 5 million people are currently co-infected with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV). HIV/HCV co-infection is associated with unique health risks including increased hepatotoxicity of antiretrovirals, accelerated progression of HCV and liver diseases. The standard in...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2013.01.026
更新日期:2013-05-01 00:00:00
abstract::The application of poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) for sustained and controlled delivery of hydrophilic insulin was made possible by preparing insulin phospholipid complex loaded biodegradable PHBHHx nanoparticles (INS-PLC-NPs). The INS-PLC-NPs produced by a solvent evaporation method showed a spher...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2011.10.072
更新日期:2012-02-01 00:00:00
abstract::To achieve an optimum drug delivery such as targeting or controlled release utilizing bioconjugation with polymeric modifier, the conjugate between drugs and polymeric modifiers must be designed to show desirable pharmacokinetic characteristics in vivo. In this study, we assessed the biopharmaceutical properties of va...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2003.10.003
更新日期:2004-07-01 00:00:00
abstract::Chemotherapeutic agents often cause severe side effects because they produce a similar cytotoxicity in both cancerous and healthy cells. In this study, a rational strategy was implemented to take advantage of a combination of both tumor microenvironment-sensitive polypeptides (TMSP) and folate to create a more selecti...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2013.02.014
更新日期:2013-05-01 00:00:00
abstract::Riboflavin (Rf) and its metabolic analogs flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential for normal cellular growth and function. Their intracellular transport is regulated by the riboflavin carrier protein (RCP), which has been shown to be over-expressed by metabolically active cancer...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2012.08.036
更新日期:2012-12-01 00:00:00
abstract::Growth factors represent highly potent and highly efficacious means of communication to cells. At the same time, these proteins are fragile and relatively small sized--rendering their immobilization and controlled release from biomaterials challenging. In this work, we establish a method to incorporate growth factors ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2015.01.036
更新日期:2015-05-01 00:00:00
abstract::Five Garren-Edwards Gastric Bubbles were characterized, following up to 4 months use in vivo, using size exclusion chromatography, differential scanning calorimetry and attenuated total reflectance infrared spectroscopy. These techniques show that the material used to construct the bubble is probably an aromatic polye...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(92)90191-p
更新日期:1992-01-01 00:00:00
abstract::The sintering behavior of calcium pyrophosphate (CPP, Ca2P2O7)-doped beta-tricalcium phosphate [TCP, Ca3(PO4)2], prepared by solid state reaction, was investigated in-situ, using dilatometry. Pure beta-TCP undergoes phase transition to alpha-TCP at about 1200 degrees C; hence pure beta-TCP ceramics should be sintered ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(01)00201-0
更新日期:2002-02-01 00:00:00
abstract::This paper describes a method of foaming a polymer system comprising poly(ethyl methacrylate)/tetrahydrofurfuryl methacrylate (PEMA/THFMA), characterisation of the resulting porosity and use of the foam for chondrocyte culture. The potential for this polymer system to support cartilage repair has been investigated pre...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2003.10.023
更新日期:2004-08-01 00:00:00
abstract::The peripheral nerve contains three barriers which include the blood-nerve barrier consisting of endoneurial vessels and the perineurium as well as autotypic junctions in Schwann cells. The perineurium prevents diffusion of perineurally injected drugs that can be used for selective regional pain control. It is compose...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2015.11.053
更新日期:2016-03-01 00:00:00
abstract::The interactions of two insoluble anticoagulant polystyrene derivatives with human platelets were studied in an in vitro system similar to a chromatography column. Blood was pumped through the column and platelets were counted before and after passage through the column. Interaction of platelets with the beads led to ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(84)90053-x
更新日期:1984-05-01 00:00:00
abstract::Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3' cholesterol (chol-siRNA) increases the activity of fre...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2010.10.019
更新日期:2011-02-01 00:00:00
abstract::Silicone elastomers have been used as implants in orthopaedics for replacements of small joints such as the metacarpophalangeal joint. A series of experiments was conducted an axially tensioned silicone elastomer tendon spacer samples to determine whether there is a relationship between stress in the material and imag...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(97)00155-5
更新日期:1998-01-01 00:00:00
abstract::The integrin α5β1 plays a major role in corneal wound healing by promoting epithelial cell adhesion and migration over the fibronectin matrix secreted as a cellular response to corneal damage. Expression of α5 is induced when rabbit corneal epithelial cells (RCECs) are grown in the presence of fibronectin. Here, we ex...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2013.05.007
更新日期:2013-09-01 00:00:00
abstract::The polymerization of N,N' carbonylbis (caprolactam) (CBC) and polyol in the presence of alcoholate as catalyst produced cross-linked poly(ester-urea)s via ring opening addition reaction. In contrast to conventional synthetic routes, the use of non-toxic CBC eliminates the need for toxic isocyanate-based monomers. The...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2003.09.110
更新日期:2004-06-01 00:00:00
abstract::We have prepared unique macroporous and ordered dextran-based hydrogels using a single-step biocatalytic transesterification reaction between dextran and divinyladipate in neat dimethylsulfoxide. These hydrogels show a unimodal distribution of interconnected pores with average diameters from 0.4 to 2.0 microm dependin...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2004.11.051
更新日期:2005-08-01 00:00:00
abstract::We have created a porous bioresorbable nanocomposite bone scaffold that chemically, structurally and mechanically matched natural bone so that it could be recognized and remodeled by natural bone. Containing collagen fibers and synthetic apatite nanocrystals, our scaffold has high strength for supporting the surroundi...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2008.07.030
更新日期:2008-11-01 00:00:00
abstract::Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype c...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2015.06.036
更新日期:2015-10-01 00:00:00
abstract::To evaluate the biocompatibility of chemically and structurally modified polyurethane elastomers for use as blood vessel replacements, small squares of vascular prostheses were cultured in direct contact with endothelium from chick embryo aorta using an organotypic culture assay. The polyurethane materials tested were...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(92)90051-o
更新日期:1992-01-01 00:00:00
abstract::We previously reported that modification of GALA peptide on the surface of liposomes enhanced fusion with endosomal membrane, and cytoplasmic release of encapsulated macromolecules. We report herein that an additional coating of GALA-modified liposomes with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer result...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2010.04.031
更新日期:2010-08-01 00:00:00
abstract::Platelet-derived growth factor BB (PDGF-BB) was an important inductive factor during wound healing, but the lack of efficient delivery system limited its clinical application. Here, a peptide of seven amino acids was firstly utilized to engineer PDGF-BB to construct a collagen-targeting system. This peptide functioned...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2006.07.023
更新日期:2006-11-01 00:00:00
abstract::Glioblastoma (GBM) is the deadliest and most common type of primary brain tumor in adults with a grim prognosis despite multimodal treatments. Dendritic cell (DC)-based immunotherapy has emerged as a promising therapeutic modality for GBM, whose efficacy is nonetheless fundamentally undermined by GBM-induced immunosup...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2018.07.035
更新日期:2018-10-01 00:00:00
abstract::Meniscus injuries are prevalent in orthopedic diagnosis. The reconstruction of the structural inhomogeneity and anisotropy of the meniscus is a major challenge in clinical practice. Meniscal tissue engineering has emerged as a potential alternative for the treatment of various meniscal diseases and injuries. In this s...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2020.120466
更新日期:2021-01-01 00:00:00
abstract::The development of an efficient colorectal cancer therapy is currently a public health priority. In the present work, we proposed a multifunctional theranostic micellar drug delivery system utilizing cationic PDMA-block-poly(ε-caprolactone) (PDMA-b-PCL) micelles as nanocarriers of SN-38 (7-ethyl-10-hydroxycamptothecin...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2016.01.068
更新日期:2016-04-01 00:00:00
abstract::In recent years, graphene and graphene-based nanocomposites owning to their highly enriched physical and chemical properties have been widely explored for applications in many different fields including biomedicine. In the present work, we decorate graphene oxide (GO) by both iron oxide nanoparticles (IONPs) and gold,...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2013.03.023
更新日期:2013-07-01 00:00:00
abstract::A synthetic process for obtaining high-molecular-weight block copolymers containing poly(lactic-glycolic acid) and poly(ethylene glycol) segments has been established. This process involves the reaction of poly(ethylene glycols) with phosgene, followed by polycondensation of the resulting alpha, omega-bis(chloroformat...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(95)96879-5
更新日期:1995-12-01 00:00:00
abstract::H2O2-specific peroxalate chemiluminescence is recognized as a potential signal for sensitive in vivo imaging of inflammation but the effect of underlying peroxalate-emitter energetics on its efficiency has rarely been understood. Here we report a simple nanophotonic way of boosting near-infrared chemiluminescence with...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2016.01.038
更新日期:2016-04-01 00:00:00
abstract::Cell detachment by laminar shear stresses was used to characterize cellular interactions with hydrophilic glass and hydrophobic silane. In this study, we examined whether smaller, rounder cells were preferentially detached by laminar flow, and whether cell detachment occurred by dissociation of adhesion proteins and t...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(93)90114-h
更新日期:1993-01-01 00:00:00
abstract::Sol-gel derived porous silica carriers for the controlled release of proteins were synthesized using a room temperature process. The materials are intended to serve as both substrates for bone growth as well as to allow incorporated proteins such as growth factors to diffuse out and stimulate cell function and tissue ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(99)00066-6
更新日期:1999-09-01 00:00:00