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 →Nature Reviews Drug Discovery2010ReviewDrug Delivery
Robby A. Petros And Joseph M. Desimone
Engineered nanoparticles have shown promise for targeted drug delivery, but first-generation systems (liposomes and polymer–drug conjugates) have not overcome all biological barriers required for effective therapy. Key barriers include opsonisation and RES clearance, inefficient cargo encapsulation and triggered…
Read the article →Journal of Internal Medicine2010ReviewNon-viral Gene Delivery
Schroeder A, Levins Cg, Cortez C, Langer R, Anderson Dg
RNAi has strong therapeutic potential, but clinical translation of siRNA is limited by delivery. siRNA is large, negatively charged, susceptible to nuclease degradation, poorly taken up by cells, and must reach the cytoplasm to engage RISC. Safe and effective lipid-based delivery systems are needed to protect siRNA…
Read the article →Angewandte Chemie International Edition2010ReviewNon-viral Gene Delivery
Knop, K.; Hoogenboom, R.; Fischer, D.; Schubert, U. S
PEG is the gold-standard stealth polymer for drug delivery, but its widespread use has revealed possible side effects and complications, including hypersensitivity, altered pharmacokinetics, toxic side products, stress-induced degradation, and non-biodegradability. This review critically discusses PEG’s advantages…
Read the article →Soft Matter2010ReviewNon-viral Gene Delivery
Parhamifar, L.; Larsen, A. K.; Hunter, A. C.; Andresen, T. L.; Moghimi, S. M
Efficient transfection with low toxicity is essential for nucleic acid therapeutics, but synthetic polycations such as polyethylenimine (PEI) are limited by cytotoxicity. This review critically assesses the safety and efficacy challenges of PEI-based polyplexes, identifies deficiencies in the field, and proposes…
Read the article →European Journal of Pharmaceutical Sciences2010ReviewNon-viral Gene Delivery
Conchita Tros De Ilarduya, Yan Sun, Nejat Düzgüneş
Viral vectors achieve high gene transfer efficiency but can induce immune/inflammatory responses, have limited DNA carrying capacity, and raise recombination and cost concerns. Non-viral vectors such as cationic lipids and polymers are safer alternatives, but their transfection efficiency—especially in vivo—remains…
Read the article →Expert Opinion on Drug Delivery2010ReviewNon-viral Gene Delivery
Zhu L, Mahato Ri
Nucleic acid therapeutics—plasmid DNA, antisense oligonucleotides, and RNAi molecules—have broad therapeutic potential but face major biological barriers, including nuclease degradation, poor membrane penetration, endosomal entrapment, nonspecific biodistribution, and immune activation. The review addresses how…
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 →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 →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 →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 →Trends in Immunology2002ReviewNon-viral Gene Delivery
James Harris, Dirk Werling, Jayne C. Hope, Geraldine Taylor, Chris J. Howard
Caveolae and caveolin are cholesterol-rich membrane microdomains involved in endocytosis, cholesterol regulation, and signal transduction, but their presence and function in immune cells have been contentious. This review addresses the need to clarify the distribution and roles of caveolae/caveolin in mammalian…
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