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The viral gene delivery systems include lytic and nonlytic vectors for drug delivery .  Tropism-modification strategies for targeted gene delivery using adenoviral . Fusogenic liposomes for intracellular delivery are also an advanced form.
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- American Journal of Advanced Drug Delivery
- Novel gene delivery systems
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Those that produce virions but leave host cell intact.
For example, adenoviruses and lentiviruses. Those that produce virions and destroy host cell. For example, human adenovirus and herpes simplex virus HSV. Antiviral and antitumor immune responses in immune competent mice upon P. Hypertension and reduction in renal failure and injury in rats with reduced renal mass on eNOS gene delivery.
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Adenoviral neutral endopeptidase gene delivery for the treatment of prostate cancer in combination with paclitaxel. Attenuation of pulmonary hypertension by targeted gene delivery of BMPR2.
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- Next Generation Delivery System for Proteins and Genes of Therapeutic Purpose: Why and How?.
Distinct roles of nucleus accumbens dopamine D2 and D3 receptors in novelty- and light-induced locomotor activity revealed using lentiviral-mediated gene delivery. Lentiviral gene delivery using fibrin hydrogels in vitro and in vivo. Maturation of human peripheral blood lymphocytes by lentiviral vectors for ex vivo gene delivery. Gene delivery to pancreatic exocrine cells in vivo and in vitro. Therapeutic gene is cloned into plasmid of HSV origin and a packaging signal, and then infected to a helper virus. Pox viruses and alphaviruses Pox viruses derived from vaccinia virus and alphaviruses derived from Togaviridae are also used as vectors.
Semliki forest virus SFV. Table 1 Viral gene delivery systems. Electroporation It is method in which small pores are produced by transmembrane potential induction of small electric impulses. Microinjection Microinjection is the process by which substances are inserted into cells at a microscopic or borderline macroscopic level using a glass pipette and performed with the help of a specialized optical microscope called micromanipulator.
American Journal of Advanced Drug Delivery
Ultrasound Nowadays ultrasound-mediated gene delivery is found to be very effective. Hydrodynamic delivery This technique mainly depends on the characteristics of blood vessels and other fluids in the body and the flow characteristics. Liposomal delivery Liposomes are vesicular structures formed by the assembly of lipid molecules themselves. Polymers Polymers are long chain compounds with either identical monomers homopolymers , or with different monomers heteropolymers , or with two different polymers copolymers.
Footnotes Source of Support: Nil Conflict of Interest: Recent progress in viral and non-viral therapy. Franceschi RT, Ge C. Gene Delivery by adenoviruses. Vectors and delivery systems in gene therapy. Zhou W, Freed CR. Adenoviral vector-mediated gene transfer for human gene therapy. Tropism-modification strategies for targeted gene delivery using adenoviral vectors. Inhibition of TGF-beta signaling in glioma cells by the integrin inhibitor.
Adenoviral neutral endopeptidase gene delivery in combination with paclitaxel for the treatment of prostate cancer. Targeted gene delivery of BMPR2 attenuates pulmonary hypertension. Retrovirus-mediated gene delivery into male germ line stem cells. Rapid production of retroviruses for efficient gene delivery to mammalian cells using T cell-based systems. Lentiviral-mediated gene delivery reveals distinct roles of nucleus accumbens dopamine D2 and D3 receptors in novelty- and light-induced locomotor activity.
Fibrin hydrogels for lentiviral gene delivery in vitro and in vivo. A simple and effective method to generate lentiviral vectors for ex vivo gene delivery to mature human peripheral blood lymphocytes. Hum Gene Ther Methods. Adeno-associated virus for cancer gene therapy. Theory and methods, perspectives for drug delivery, gene therapy and research. Delivery of a DNA vaccine for Alzheimer's disease by electroporation versus gene gun generates potent and similar immune responses.
Short noncoding DNA fragment improve efficiencies of in vivo electroporation-mediated gene transfer. Gene gun bombardment with DNA-coated golden particles enhanced the protective effect of a DNA vaccine based on thioredoxin glutathione reductase of Schistosoma japonicum. Improvement of DNA vaccines by electroporation.
Gene delivery by direct injection microinjection using a pulsed-flow system. Cationic versus neutral microbubbles for ultrasound-mediated gene delivery in cancer. Ultrasound and microbubble-assisted gene delivery: Recent advances and ongoing challenges. Efficient reduction of serum cholesterol by combining a liver-targeted gene delivery system with chemically modified apolipoprotein B siRNA. Liposomes as a gene delivery system. Braz J Med Biol Res. Lipid carrier systems for targeted drug and gene delivery. Chem Pharm Bull Tokyo ; Cullis PR, Chonn A. Recent advances in liposome technologies and their applications for systemic gene delivery.
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Adv Drug Deliv Rev. Advances in liposome-based targeted gene therapy of cancer. Recent Advances in Cancer Research and Therapy. Assessment of therapeutic efficacy of liposomal nanoparticles mediated gene delivery by molecular imaging for cancer therapy. Current advances in vehicles for brain gene delivery. Current status of polymeric gene delivery systems. Akhtar S, Benter I. Toxicogenomics of non-viral drug delivery systems for RNAi: Potential impact on siRNA-mediated gene silencing activity and specificity.
A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene transfection reagent. J Am Chem Soc. Theoretical and computational studies of dendrimers as delivery vectors. Carbosilane dendrimers are a non-viral delivery system for antisense oligonucleotides: Computational and experimental insights. In the present review, snapshots about the benefits of proteins or gene therapy, general procedures for therapeutic protein or gene delivery system, and different next generation delivery system such as liposome, PEGylation, HESylation, and nanoparticle based delivery have been depicted with their detailed explanation.
Over the last few years, numerous therapeutic proteins and peptides have been approved for clinical usage. Till date, more than different therapeutic proteins and genes have been approved by US-FDA for clinical use, and various therapeutic proteins are in the process of development [ 1 , 2 ]. It was a landmark discovery in the medical science when insulin was purified from bovine and porcine pancreas and was utilized as a life-saving injection for patients with type I diabetes mellitus T1DM in [ 3 ].
At that time, some issues were associated with this insulin treatment such as availability of animal pancreases especially bovine and porcine pancreases, immunogenicity of animal insulin to some patients, and cost of the protein [ 4 ]. The problem was solved through recombinant DNA technology, which helped in the production of recombinant insulin using E. Insulin was the first commercially available recombinant therapeutic protein, approved by the US-FDA in , and presently is the most significant treatment for T1DM [ 8 , 9 ].
Presently, with the help of biotechnology and recombinant DNA technology, several recombinant therapeutic proteins are being developed and marketed as biopharmaceutical, and the sales value of these recombinant proteins has gained the highest level of market share in pharmaceutical sector [ 10 , 11 ]. With the beginning of recombinant DNA technology, the idea was to use nucleic acids to cure diseased cells, especially in cells where gene is deleted or mutated.
After this report, there have been many debates on pros and cons of gene therapy technology [ 13 ]. However, slowly, due to novel advantages of gene therapy, it is entering into the mainstream of treatment. More than gene therapy clinical trials have been completed throughout the world and many are continuing [ 14 ]. Therefore, developing efficient gene delivery technology is one of the significant areas for pharmaceutical industry in current era [ 15 ].
Presently, pharmaceutical delivery system PDS or drug delivery system DDT is very important for the pharmaceutical industry. Many pharmacological properties of traditional molecules can be improved with the help of DDS [ 16 , 17 ]. The effectiveness and marketability of the drug molecules depend on the mode of DDS. Pharmaceutical industries are prone to generate new DDS which can impart novel properties to existing as well as newly discovered products. New DDS will be more efficient and safer compared to the existing one [ 18 ].
It has been noted that market value, competitiveness, and patent life may boost up for an existing drug candidate molecule if we use a new DDS. Therefore, the existing drug candidate molecules may offer a new opportunity to increase the market price and competitiveness in the pharmaceutical market [ 21 ]. Conversely, patent expiry is one of the major alarms for the pharmaceutical industry. A new DDS can provide a new marketability to an existing drug molecule. Therefore, the development of novel delivery systems is at high priority for the pharmaceutical companies to capture global market.
Biopharmaceuticals especially therapeutic proteins and gene therapy are one of the fastest growing areas of the pharmaceutical business. The first generation therapeutic protein based drugs are currently passing through a number of difficulties and needs for improvement.
Novel gene delivery systems
One the other hand, the efficient gene delivery system can improve the means for delivering genes during gene therapy and thus can contribute toward more successful clinical outcomes [ 24 ]. In this paper, we have tried to highlight next generation delivery systems and benefits of proteins therapy or gene therapy. Efforts have been made to summarize general procedures for therapeutic protein or gene delivery system and different next generation delivery systems, namely, liposome, PEGylation, HESylation, and nanoparticle based delivery along with their detailed description.
Over the last few years, biopharmaceuticals especially therapeutic proteins have received great attention. Among the biopharmaceuticals, therapeutic proteins and genes delivery have gained the maximum percentage of market share [ 25 ]. It has been found that protein therapeutics has some advantages over small-molecule drug molecules, which may be summarized as follows.
This treatment can help us without any gene therapy. It is very difficult to imitate this distinctive possessed function of enzymes by simple chemicals. So, there is very little chance for the hindrance of normal biological processes with the therapeutic proteins that cause unsympathetic effect. Since these proteins are produced from our body itself, they are well tolerated.
Therefore, the chance of failure is fewer during the clinical trials. From financial point of view, these benefits make therapeutic protein attractive to the pharmaceutical industry [ 1 , 26 ]. Gene therapy may provide novel treatments for diseases having no effective conventional treatment. Gene therapy can be the ultimate solution for genetic disorders, as it can help to replace deleted or mutated gene for correcting genetic disorders. This possibility of amending genetic disorder is gaining importance and researches are trying to deliver genes to the affected cells.
Major factor affecting efficacy for gene therapy is gene delivery system. The refinements to the delivery system may increase security as well as the long-term expression of the gene of interest and reduce the chance of mutagenesis of the particular gene. After gene replacement therapy, the patient needs not receive the treatment of protein based therapeutics regularly, making it one of the desired lines of treatment [ 27 , 28 ]. Other than the above benefits, some limitations have been noted of therapeutic proteins and genes.
The main disadvantage is the stability associated with these proteins or genes which is often not proper. The half-life is also limited. Immunogenicity is another problem for therapeutic protein or genes. For the therapeutic proteins, it has also been observed that light sensitivity, moisture, temperature, and so forth, hamper their stability.
Many strategies have been undertaken to improve these limitations. Among them, two strategies are frequently being employed: Proteins are generally conjugated with natural or synthetic polymers PEGylation, HESylation, and polysialylation to alter structure of therapeutic proteins [ 31 , 32 ].
Conversely, different drug formulation systems are also being used to overcome the existing limitations of therapeutic proteins. These formulation systems are polymeric microspheres, polymeric nanoparticles, liposomes, and so forth [ 33 ]. For gene delivery, viral vectors and nonviral vectors are usually used.
The efficiency of a number of drugs is often limited by their potential to reach the site of therapeutic effect. In most cases, only a small amount of a controlled dose reaches the target site, while the majority of the drug allocates throughout the rest of the body in accordance with its physic-chemical and biochemical properties. Therefore, it is very challenging task to enhance the pharmaceutical effect of drugs while reducing its toxicity in vivo. These objectives can only be achieved through next generation delivery system.
Lipid molecules of biomembranes interacting with water molecules can control the transport phenomena and protein functions with anisotropic flow experience. After the discovery in , liposomes were used for delivery of peptide and protein drugs [ 38 — 41 ]. By following authors Lazhen Shen.
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One email with all search results. One email for each search. Materials , 11 2 , ; https: In this review, we first list the three commonly utilized synthesis methods of Fe 3 O 4 NPs, and their advantages and disadvantages. Then our efforts will be devoted to the research status and progress of several different functionalized Fe 3 O 4 NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail.
In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy.