Journal of Drug Targeting (J Drug Target)2013ReviewNon-viral Gene Delivery
Jing Yao, Ying Fan, Yuanke Li, And Leaf Huang
Non-viral gene delivery systems are safer than viral vectors but are highly inefficient at nuclear delivery. Only ~10–20% of applied plasmid DNA enters targeted cells, and only ~1–5% of the applied dose reaches the nucleus. The nuclear envelope is a major barrier to transgene delivery, and there is a need for “smart”…
Read the article →Pharmaceutical Research2011ResearchNon-viral Gene Delivery
Samar Hamdy, Azita Haddadi, Anooshirvan Shayeqanpour, John Samuel, Afsaneh Lavasanifar
Mannosylation of vaccine formulations is a promising strategy to target antigens to the mannose receptor (MR) on dendritic cells (DCs), potentially improving antigen uptake, processing, and presentation. While PLGA nanoparticles (NPs) are established vaccine delivery vehicles, the effect of chemical conjugation of…
Read the article →2011ReviewNon-viral Gene Delivery
Chou Lyt, Ming K, Chan Wcw.
Nanoparticles (NPs) are increasingly used as contrast agents, therapeutics, and delivery vehicles, but their effective delivery into cells and to specific subcellular organelles remains a major challenge. The review addresses fundamental barriers to intracellular NP delivery—plasma membrane, endosomal entrapment…
Read the article →2011ReviewDrug Delivery
Torchilin Vp
Lipid-based nanocarriers such as liposomes and micelles can protect drugs, reduce nonspecific toxicity, and improve pharmacokinetics, but conventional formulations are limited by rapid clearance, poor targeting, and inefficient intracellular delivery. Engineering “multifunctional pharmaceutical nanocarriers” that…
Read the article →2011ReviewNon-viral Gene Delivery
Kim, T.-I.; Kim, S. W
Bioreducible polymers containing disulfide linkages are attractive gene-delivery carriers because they are stable in the oxidizing extracellular environment but degrade rapidly in the reducing intracellular cytosol via thiol–disulfide exchange, triggered by high glutathione (GSH) levels. This review addresses the…
Read the article →Polymers2011ReviewDrug Delivery
Hirenkumar K. Makadia And Steven J. Siegel
PLGA has become one of the most attractive biodegradable polymers for drug delivery and tissue engineering, but its degradation and drug-release behaviour depend on many interconnected variables—polymer composition, molecular weight, crystallinity, device geometry, fabrication method, and drug type. A consolidated…
Read the article →Gene Therapy2010ReviewNon-viral Gene Delivery
Lam Ap, Dean Da.
The nuclear envelope remains a major barrier to successful nonviral transfection and gene therapy. After exogenous DNA is delivered to the cytoplasm, it rapidly complexes with cellular proteins that control its intracellular trafficking and nuclear import. Understanding these mechanisms is necessary to improve…
Read the article →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 →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 →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 →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 →Biochimica et Biophysica Acta (BBA) - Biomembranes2005ResearchNon-viral Gene Delivery
Mattias Hallbrink, Johannes Oehlke, Gisela Papsdorf, Michael Bienert
Cell-penetrating peptides (CPPs) efficiently translocate across plasma membranes and are promising delivery vectors for therapeutic macromolecules. However, the influence of cell state, density, and peptide-to-cell ratio on CPP uptake and degradation has received little attention. Understanding whether CPP uptake is…
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 →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 →Gene Therapy1999ResearchNon-viral Gene Delivery
J Vacik, Bs Dean, We Zimmer, Da Dean
Non-viral gene therapy vectors lack efficient cell-specific targeting, with most approaches focusing only on cell surface internalisation rather than nuclear delivery. The nuclear import of plasmid DNA is a critical barrier to gene expression, yet it has been largely overlooked in vector design. A method to achieve…
Read the article →Gene Therapy1999ResearchNon-viral Gene Delivery
Sérgio Simões, Vladimir Slepushkin, Pedro Pires, Rogério Gaspar, Maria C. Pedroso De Lima & Nejat Düzgüneş
Cationic liposome–DNA complexes (lipoplexes) are safer than viral vectors but have limited transfection efficiency, toxicity at high doses, and sensitivity to serum/extracellular negatively charged macromolecules. The study asks whether targeting ligands or pH-sensitive fusogenic peptides can improve…
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