Chemical Reviews2015ReviewNon-viral Gene Delivery
Ulrich Lächelt And Ernst Wagner
Therapeutic nucleic acids—including plasmid DNA, mRNA, siRNA, miRNA, antisense oligonucleotides, and aptamers—have broad therapeutic potential, but their delivery to the correct intracellular site of action remains the dominant bottleneck. Polyplexes, formed by electrostatic complexation of nucleic acids with…
Read the article →Nanoscale2014ReviewNon-viral Gene Delivery
Da Ma
siRNA-based gene therapy is a promising biotechnology for treating cancer and other diseases, but safe and efficient delivery is essential. Nanoparticle-mediated delivery must overcome multiple biological barriers, and endosomal escape is a critical rate-limiting barrier: nanoparticles are typically internalised via…
Read the article →2014ReviewNon-viral Gene Delivery
Singh Ms, Bhaskar S.
Cancer immunotherapy can induce specific antitumor immunity, control metastases, and provide immunological memory, but faces barriers including immunosuppressive tumour microenvironments and poor delivery of immunomodulators. Nanocarriers offer a versatile way to deliver antigens, adjuvants, cytokines, antibodies…
Read the article →Nature Reviews Genetics2014ReviewNon-viral Gene Delivery
Yin H, Kanasty Rl, Eltoukhy Aa, Vegas Aj, Dorkin Jr, Anderson Dg.
Gene-based therapy has potential to treat a wide range of diseases, but clinical success is limited by delivery barriers. Viral vectors, while efficient, carry risks of carcinogenesis, immunogenicity, broad tropism, limited packaging capacity, and manufacturing difficulties. Non-viral vectors offer improved safety…
Read the article →European Journal of Pharmaceutics and Biopharmaceutics.2014ReviewNon-viral Gene Delivery
Slavomíra Doktorovová, Eliana B. Souto, Amélia Maria Silva
Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were developed as alternative colloidal carriers with better stability and tolerability than polymeric nanoparticles. However, in vitro toxicity data were scattered across many cell lines, assays, exposure times, concentrations, and formulations…
Read the article →Journal of Controlled Release2014ReviewNon-viral Gene Delivery
Lee, Y. S.; Kim, S. W
Cationic polymeric gene carriers are promising non-viral vectors, but their slow degradability and intracellular/tissue accumulation cause cytotoxicity. Bioreducible polymers containing disulfide linkages are attractive because they are stable extracellularly but degrade selectively in the reducing intracellular…
Read the article →Molecular Therapy.2013ReviewNon-viral Gene Delivery
El-Sayed A, Harashima H
Nonviral gene delivery vectors remain less efficient than viral vectors, and their intracellular fate is strongly influenced by the endocytic route they enter. The cell membrane is now understood to contain lipid raft and non-raft domains, and the initial binding domain can determine the primary endocytic vesicle…
Read the article →Drug Discovery Today.2013ReviewDrug Delivery
Gan L, Wang J, Jiang M, Bartlett H, Ouyang D, Eperjesi F, Liu J, Gan Y
Topical ocular drug delivery is limited by tear turnover, corneal and conjunctival barriers, efflux transporters, and poor water solubility of many drug candidates. Lipid-based nanocarriers may improve ocular bioavailability, prolong preocular residence, enhance corneal penetration, and provide controlled release…
Read the article →Journal of Controlled Release2013ReviewNon-viral Gene Delivery
Ragelle, H.; Vandermeulen, G.; Préat, V
Chitosan is attractive for siRNA delivery because it is cationic, biocompatible, biodegradable, mucoadhesive, and permeation-enhancing. However, native chitosan suffers from low solubility at physiological pH, poor buffering capacity, instability in biological fluids, and insufficient endosomal escape, limiting…
Read the article →2012ReviewNon-viral Gene Delivery
Zhang X-X, Mcintosh Tj, Grinstaff Mw
Cationic lipids are the most common non-viral gene-delivery vectors, but they generally suffer from low transfection efficiency. Functional or stimulus-responsive lipids—especially pH-, redox-, and charge-reversal-sensitive lipids—may improve nucleic acid delivery by enabling triggered cargo release, endosomal…
Read the article →Chemical Society Reviews2012ReviewDrug Delivery
Samal, S. K.; Dash, M.; Van Vlierberghe, S.; Kaplan, D. L.; Chiellini, E.; Van Blitterswijk, C.; Moroni, L.; Dubruel, P
Cationic polymers are widely studied as non-viral gene delivery vectors, but their therapeutic potential extends well beyond gene delivery. This review addresses the need for a broader overview of cationic polymers — their synthesis, modification, bioactive properties, architectures, and applications in drug…
Read the article →Journal of Controlled Release2012ReviewDrug Delivery
Fabienne Danhier, Eduardo Ansorena, Joana M. Silva, Regis Coco, Aude Le Breton, Véronique Préat
PLGA is one of the most successfully developed biodegradable polymers, with FDA and EMA approval for parenteral drug delivery, but a comprehensive overview linking its formulation methods, physicochemical pitfalls, targeting strategies, and applications across multiple diseases was needed. This review presents why…
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 →Journal of Drug Delivery2011ReviewNon-viral Gene Delivery
Daniel A. Balazs, W.T. Godbey
Liposomes are versatile, biocompatible vesicular carriers that can encapsulate and deliver DNA or RNA, but the relationship between lipid charge, lipid packing, and gene-delivery efficiency remains complex. This review discusses physical packing parameters and specific lipids used for gene delivery, classified by…
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 →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 →