Microneedles vs. Other Transdermal Technologies
Boris Stoeber, Raja K Sivamani, Howard I. Maibach in Microneedling in Clinical Practice, 2020
The original biolistic particle delivery system, or gene gun, was designed for delivering exogenous DNA (transgenes) into plant cells. The payload is typically a particle of a heavy metal coated with DNA (typically plasmid DNA). This has been developed into biolistic injectors delivering a “shotgun” burst of nano- or microparticles into the skin (Figure 5.5 right), injectors that have been effective for the immunization of antigens including influenza and malaria, and also in anticancer applications in a range of animals (mice, rat, ferrets, monkeys, etc.) and humans (79–82). Clinical assessment of biolistic particle delivery reports transient localized pain and tissue damage (erythema, irritation, etc.); thus, like liquid biolistic injection, the technique is most suitable to vaccination.
Methods for Labeling Nonphagocytic Cells with MR Contrast Agents
Michel M. J. Modo, Jeff W. M. Bulte in Molecular and Cellular MR Imaging, 2007
Mechanical approaches that have been used primarily to introduce DNA or plasmids into the nucleus have been modified to directly introduce MRI contrast agents into cells. The gene gun fires DNA, plasmids, or DNA-coated nanoparticles directly into cells in culture, driving the particles through the cell membrane or directly into the nucleus,96,97 using a ballistic gas charge. SPIO nanoparticles and magnetic beads have been introduced into stem cells using a gene gun with high labeling efficiency,98 and the cells were implanted into rats, but no information was provided about the effects of the method on long-term cell viability, proliferation, differentiation capabilities, or reactive oxygen species. It should be noted that the gene gun approach is indiscriminant and will introduce MRI SPIO nanoparticles directly into the cell nucleus. Although it is beneficial to deliver DNA directly into the nucleus, the presence of SPIO nanoparticles in the nucleus could initiate a Fenton reaction and, through Haber-Weiss chemistry,99 result in the development of free radicals that could cause damage to DNA.
Adeno-Associated Virus-Based Delivery Systems
Kenneth L. Brigham in Gene Therapy for Diseases of the Lung, 2020
Stable gene transduction in skeletal muscle would be desirable both as a treatment of primary muscle disorders and as an in vivo reservoir for soluble circulating proteins such as insulin in diabetes. One group has developed AAV gene transfer to cultured human myoblasts with the goal of later injection into skeletal muscle (163). AAV was the basis of the plasmid pCKM-gfp, a construct using the human CKMmuscle promoter and the green fluorescent protein cDNA as the reporter gene. The cell line was transfected using the gene gun (BioRad) and gold microspheres coated with plasmid DNA. This gene gun accomplished between 1% and 5% transfection efficiency after 4 days in culture. Injection of the naked plasmid DNA directly into murine quadriceps skeletal muscle resulted in much higher efficiency at 4 days, leading the authors to speculate that maximal activity may require differentiated or multinucleated cells. However, it has been observed with other vectors that naked plasmid DNA is very effective in skeletal and cardiac muscle in general (164-172).
Advances and challenges in nintedanib drug delivery
Published in Expert Opinion on Drug Delivery, 2021
Varalakshmi Velagacherla, Akhil Suresh, Chetan H Mehta, Usha Y Nayak
Solid-powder injectors deliver various therapeutically active molecules into superficial skin layers in their dry form. This delivery is also named gene gun and biolistic injectors as it can be used for delivering the gene as well as biological molecules such as DNA and others [103]. The design includes a compartment for storing drug or solid powdered formulation, a power source that includes compressed gas, and a nozzle for delivering the solid particles or particles flow. On one press, compressed gas carries the drug or formulation exits from the nozzle, imposes on the skin, and causes puncturing of the micron dimensional stratum corneum holes through their momentum, which finally reached the desired site for showing their therapeutic effect [105–107]. The velocity of impact, the radius of the drug or formulation particle and its density, and finally the payload of the particle are some of the important parameters that need to be considered during the delivery of the drug particles through the stratum corneum. Some of the studies that are used in this technique showed successful delivery of drugs without any pain, which indicates the safety of the technique [108–115]. The examples of novel transdermal drug delivery devices are given in Table 6.
GOLD: human exposure and update on toxic risks
Published in Critical Reviews in Toxicology, 2018
Technology developed in the University of Wisconsin highlights a “gene gun” which was claimed to fire a DNA-tipped gold bullet to inhibit growth of murine tumours (Franklin 1965). This novel therapy was designed to alter the genome of cancers cells thereby making them susceptable to destruction by the body’s own immune system. Genes prepared using conventional cloning were then precipitated onto gold beads (1 nm) which were injected into tumors by a pulse of compressed helium. At the time, Professor Karol Sikora of Imperial College, London is reported as saying that “gene therapy is designed to get the foreign DNA to the right place. The gene gun is one of a number of approaches, each of which has advantages and disadvantages”. Sikora saw the gene gun as an interesting approach. Whilst gold has no clear action as a cytotoxic agent here, it is biocompatible in the human body and is potenially valuable as an anticancer therapy (Tiekink 2008; Powell et al. 2010; Paciotti et al. 2004; Gasull 2012; Murawala et al. 2014).
Advanced physical techniques for gene delivery based on membrane perforation
Published in Drug Delivery, 2018
Xiaofan Du, Jing Wang, Quan Zhou, Luwei Zhang, Sijia Wang, Zhenxi Zhang, Cuiping Yao
To date, there are many techniques can achieve this goal including biological, chemical, mechanical and physical methods (Mehier-humbert & Guy, 2005; Kim & Eberwine, 2010). Biological method, such as virus-mediated method, is easy to use and with high efficiency (Kim & Eberwine, 2010). But it has potentially risk that viral vectors may infect healthy cell adjacent to the target cell (Moss, 2014), even can lead to patient death because of inflammatory immune responses induced by adenoviral vectors (Chuah et al., 2003), and the size of genetic materials inserted into cell is limited (El-Aneed, 2004; Lv et al., 2006). Chemical methods commonly include calcium phosphate coprecipitation, high molecular weight cationic polymers, cationic lipid and cationic amino acid (Holmen et al., 1995; Washbourne & McAllister, 2002; Kim & Eberwine, 2010; Todorova, 2011). Compared with biological method, the chemical method has advantages of no size limitation and less cytotoxicity. However, the transfection efficiency is lower than biological method (Washbourne & McAllister, 2002; Kim & Eberwine, 2010). For the mechanical methods, such as micro injection (Zhang & Yu, 2008), ballistic (gene gun) (Sun et al., 1998; Trimble et al., 2003), are invasive and cell-damageable. Microinjection is to penetrate the cell membrane with the help of micropipette and deliver the nucleic acids into the cytoplasm (Bora, 2014), which has highly technical and experiential demands for operators. The principle of gene gun is to shot the nucleic acids coated by particles into cell with the help of air pressure (Herrero et al., 2017). However, the air pressure may damage the cell.