Journal of Microencapsulation2009ResearchDrug Delivery
Jaber Emami, Hamed Hamishehkar, Abdolhossien Rouholamini Najafabadi, Kambiz Gilani, Mohsen Minaiyan, Hamid Mahdavi, Hamid Mirzadeh, Amir Fakhari, Ali Nokhodchi
Pulmonary administration offers a route for systemic delivery of therapeutics, especially peptides and proteins, but controlled-release polymer particles are needed. Conventional w/o/w methods for hydrophilic drugs suffer from low encapsulation, protein inactivation, and difficult release control. An oil-in-oil (o/o)…
Read the article →Experimental and Molecular Pathology2009ReviewDrug Delivery
Singh R, Lillard Jw Jr.
Nanotechnology enables control and manufacture of structures in the nanometer range, and nanoparticles exhibit novel properties that differ from bulk materials. There is a need for targeted drug delivery systems that improve solubility, bioavailability, sustained release, protection from degradation, and…
Read the article →2009ReviewNon-viral Gene Delivery
Sunshine, J.; Bhise, N.; Green, J. J
Non-viral gene delivery needs safe and effective carriers. PEI is effective but cytotoxic, while viral vectors raise safety concerns. Degradable poly(β-amino ester)s may provide effective gene delivery with reduced cytotoxicity. This study investigates how small changes in polymer synthesis ratio and end-group…
Read the article →British Journal of Pharmacology2009ReviewNon-viral Gene Delivery
Midoux P, Pichon C, Yaouanc J-J, Jaffrès P-A
Non-viral nucleic acid delivery systems—lipoplexes, polyplexes, and lipopolyplexes—are limited mainly by poor endosomal escape. The review examines whether histidine- and imidazole-containing carriers can exploit the acidic endosomal environment to destabilize membranes and improve cytosolic delivery of DNA, mRNA…
Read the article →International Journal of Pharmaceutics2008ResearchNon-viral Gene Delivery
Yongxin Yang, Zhenghong Xu, Shangwei Chen, Yu Gao, Wangwen Gu, Lingli Chen, Yuanying Pei, Yaping Li
Cationic polymers are widely studied non-viral gene vectors but generally show lower transfection efficiency than viral vectors. Endosomal escape is a major bottleneck. Histidine/imidazole-containing polymers can enhance gene expression via a “proton sponge” effect without increasing toxicity. Polyphosphazenes are…
Read the article →Vaccine2008ResearchNon-viral Gene Delivery
S. Hamdy, O. Molavi, Z. Ma, A. Haddadi, A. Alshamsan, Z. Gobti, S. Elhasi, J. Samuel, A. Lavasanifar
Most PLGA-based cancer vaccine studies used foreign model antigens such as ovalbumin (OVA), which are not subject to central/peripheral tolerance and can overestimate therapeutic efficacy. There is a need to evaluate PLGA vaccines against a realistic, clinically relevant self/tumor antigen (TRP2) and to overcome…
Read the article →Journal of Pharmaceutical Sciences2008ReviewDrug Delivery
Prokop A, Davidson Jm.
Conventional drug delivery faces barriers including rapid clearance, poor intracellular uptake, low target specificity, and toxicity. Nanovehicles (NVs)—nanosized particles capable of entering cells and delivering cargo intracellularly—offer a means to overcome these barriers. The review aims to provide an overview…
Read the article →Accounts of Chemical Research2008ReviewNon-viral Gene Delivery
Green, J. J.; Langer, R.; Anderson, D. G
Gene therapy has enormous therapeutic potential, but delivery remains the central bottleneck. Viral vectors are efficient but carry serious safety, immunogenicity, manufacturing, and cargo-capacity limitations. Nonviral vectors are safer and more scalable but typically orders of magnitude less effective. This Account…
Read the article →Journal of drug targeting2008ReviewDrug Delivery
Parveen, S.; Sahoo, S. K
Conventional cancer chemotherapy suffers from poor tumour selectivity, high required doses, systemic toxicity, rapid drug elimination, and multidrug resistance. Polymeric nanoparticles (NPs) are reviewed as a strategy to improve targeted delivery, controlled release, and therapeutic efficacy while reducing adverse…
Read the article →Journal of Controlled Release2007ResearchNon-viral Gene Delivery
Ayumi Sato, Sung Won Choi, Miwa Hirai, Asako Yamayoshi, Rui Moriyama, Takeshi Yamano, Motoki Takagi, Arihiro Kano, Akira Shimamoto, Atsushi Maruyama
Systemic siRNA therapeutics are limited by poor cell membrane permeability, rapid nuclease degradation, and renal clearance. A carrier with long circulatory half-life is needed for effective RNAi and potential tumour targeting via the enhanced permeation and retention (EPR) effect. Existing hydrophilic…
Read the article →Molecular Pharmaceutics2007ResearchNon-viral Gene Delivery
C. M. Solbrig, J. K. Saucier-Sawyer, V. Cody, W. M. Saltzman, D. J. Hanlon
Current antitumor vaccines are limited by the small number of defined tumour-associated antigens (TAAs) for most solid tumours and by poor delivery of soluble antigen to dendritic cells (DCs). Autologous whole-tumour lysates contain the full antigenic repertoire, but soluble lysates are unstable and poorly…
Read the article →2007ReviewNon-viral Gene Delivery
Li W, Szoka Fc Jr
Systemic non-viral gene delivery is limited by rapid clearance, toxicity, and poor target-cell access. Cationic lipid–DNA lipoplexes are effective in vitro but perform poorly in vivo because they aggregate with serum proteins, are cleared by the reticuloendothelial system (RES), and accumulate mainly in lung and…
Read the article →Journal of Controlled Release2007ReviewNon-viral Gene Delivery
Gary, D. J.; Puri, N.; Won, Y.-Y
Polymer-based siRNA delivery is promising but faces limitations similar to polymer-based DNA delivery, yet the two nucleic acids differ fundamentally in size, stiffness, stability, site of action, and duration of effect. This review addresses the need to understand these distinctions so that knowledge from the…
Read the article →Bioconjugate Chemistry2006ResearchNon-viral Gene Delivery
Jordan J. Green, Julie Shi, Eugene Chiu, Elizaveta S. Leshchiner, Robert Langer, Daniel G. Anderson
Effective and safe gene delivery to primary endothelial cells in the presence of serum proteins is particularly challenging. Endothelial cells are important targets for cardiovascular disease and cancer, but existing nonviral vectors have low efficacy and/or cytotoxicity under serum-containing conditions. C32…
Read the article →Journal of Controlled Release2006ResearchNon-viral Gene Delivery
DNA vaccines are limited by inefficient delivery to antigen-presenting cells (APCs) and lack of adjuvant effect, especially for weakly immunogenic self/tumor antigens. The study addresses this by using cationic PEI-functionalised PLGA microparticles to enhance APC activation and protective anti-tumour immunity…
Read the article →Expert Opinion on Therapeutic Patents2006ReviewNon-viral Gene Delivery
Mcneil Se, Perrie Y
Cationic liposomes have been developed for gene delivery for almost 20 years, but despite extensive effort, there has been limited progress toward an effective pharmaceutical product. Their transfection efficiency remains insufficient, and most clinical trials still rely on more potent viral vectors despite viral…
Read the article →Nature Materials2006ReviewNon-viral Gene Delivery
Putnam D
Synthetic polymer-based gene delivery vectors have been studied for two decades but remain far less efficient than viral vectors. The review addresses the need for improved design criteria and new synthetic strategies across nano-, micro-, and macroscale delivery systems to overcome formulation, organism-level, and…
Read the article →Journal of Controlled Release2006ReviewNon-viral Gene Delivery
Lv H, Zhang S, Wang B, Cui S, Yan J
Cationic lipids and polymers are promising non-viral gene delivery vectors because they are non-immunogenic, easy to produce, and not oncogenic, but toxicity remains a major obstacle to their clinical application. The review evaluates structural features of cationic compounds and summarises toxicity–structure…
Read the article →Gene Therapy2005ReviewNon-viral Gene Delivery
Dean Da, Strong Dd, Zimmer We.
Nonviral gene delivery is limited by multiple extracellular and intracellular barriers, but the nuclear envelope remains a major unresolved barrier, especially in nondividing cells. Plasmids must enter the nucleus to be transcribed, yet the mechanisms of plasmid nuclear import are much less understood than protein…
Read the article →Expert Opinion on Drug Delivery2005ReviewNon-viral Gene Delivery
Sérgio Simões, Ana Da Silva Filipe, Henrique Faneca, Miguel Mano, Nuno Penacho, Nejat Düzgüneş, Maria C. Pedroso De Lima
Cationic liposome–DNA complexes (lipoplexes) are a potentially viable non-viral alternative to viral vectors for therapeutic gene delivery, but they suffer from limited delivery/gene expression efficiency, toxicity at higher concentrations, adverse interactions with serum and cell surfaces, and poor tissue access…
Read the article →Nature Reviews Drug Discovery2005ReviewNon-viral Gene Delivery
Pack, D. W.; Hoffman, A. S.; Pun, S.; Stayton, P. S
The lack of safe and efficient gene-delivery methods remains a limiting obstacle to human gene therapy. Synthetic vectors are safer than recombinant viruses but generally lack sufficient efficacy, so polymers must be rationally designed to overcome extracellular and intracellular delivery barriers. PEI: Only 15–20%…
Read the article →Advanced Drug Delivery Reviews2005ReviewNon-viral Gene Delivery
Ying Waeckerle-Men And Marcus Groettrup
Dendritic cell (DC)-based vaccines are limited by the short persistence of MHC class I/peptide complexes on the DC surface—often only a few hours—when soluble peptides are loaded exogenously. This short presentation limits CTL activation and vaccine efficacy. The authors investigated biodegradable PLGA microspheres…
Read the article →Synthesis of Poly(β-amino esters) Optimized for Highly Effective Gene Delivery.2003ResearchNon-viral Gene Delivery
Akinc, A., Anderson, D. G., Lynn, D. M., & Langer, R. (2003).
Nonviral polymeric gene delivery vectors need systematic optimisation of nonstructural factors—polymer molecular weight, chain end-group, and polymer/DNA ratio—that strongly influence transfection, cytotoxicity, and DNA complexation. These factors had not been comprehensively studied together for poly(β-amino…
Read the article →Molecular Therapy2001ResearchNon-viral Gene Delivery
Adi Mesika, Irina Grigoreva, Muriel Zohar, Ziv Reich
Transfection efficiency of nonviral gene delivery systems remains unacceptably low, largely due to the inability of plasmid DNA to effectively translocate through the nuclear pore complexes (NPCs). While substantial progress has been made in transcriptionally regulated vectors, control over nuclear targeting is…
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