Jagadeesh Gopalan

Laser-ablation-assisted microparticle acceleration for drug delivery

Localized drug delivery with minimal tissue damage is desired in some of the clinical procedures such as gene therapy, treatment of cancer cells, treatment of thrombosis, etc. We present an effective method for delivering drug-coated microparticles using laser ablation on a thin metal foil containing particles. A thin metal foil, with a deposition of a layer of microparticles is subjected to laser ablation on its backface such that a shock wave propagates through the foil. Due to shock wave loading, the surface of the foil containing microparticles is accelerated to very high speeds, ejecting the deposited particles at hypersonic speeds. The ejected particles have sufficient momentum to penetrate soft body tissues, and the penetration depth observed is sufficient for most of the pharmacological treatments. We have tried delivering 1 \mu m tungsten particles into gelatin models that represent soft tissues, and liver tissues of an experimental rat. Sufficient penetration depths have been observed in these experiments with minimum target damage.

Successful treatment of biofilm infections using shock waves combined with antibiotic therapy.

Many bacteria secrete a highly hydrated framework of extracellular polymer matrix on suitable substrates and embed within the matrix to form a biofilm. Bacterial biofilms are observed on many medical devices, endocarditis, periodontitis and lung infections in cystic fibrosis patients. Bacteria in biofilm are protected from antibiotics and >1,000 times of the minimum inhibitory concentration may be required to treat biofilm infections. Here, we demonstrated that shock waves could be used to remove Salmonella, Pseudomonas and Staphylococcus biofilms in urinary catheters. The studies were extended to a Pseudomonas chronic pneumonia lung infection and Staphylococcus skin suture infection model in mice. The biofilm infections in mice, treated with shock waves became susceptible to antibiotics, unlike untreated biofilms. Mice exposed to shock waves responded to ciprofloxacin treatment, while ciprofloxacin alone was ineffective in treating the infection. These results demonstrate for the first time that, shock waves, combined with antibiotic treatment can be used to treat biofilm infection on medical devices as well as in situ infections.

Remotely triggered micro-shock wave responsive drug delivery system for resolving diabetic wound infection and controlling blood sugar levels

A novel, micro-shock wave responsive spermidine and dextran sulfate microparticle was developed. Almost 90% of the drug release was observed when the particles were exposed to micro-shock waves 5 times. Micro-shock waves served two purposes; of releasing the antibiotic from the system and perhaps disrupting the S. aureus biofilm in the skin infection model. A combination of shock waves with ciprofloxacin loaded microparticles could completely cure the S. aureus infection lesion in a diabetic mouse model. As a proof of concept insulin release was triggered using micro-shock waves in diabetic mice to reduce the blood glucose level. Insulin release could be triggered for at least 3 days by exposing subcutaneously injected insulin loaded particles.

Mechanism of transformation in Mycobacteria using a novel shockwave assisted technique driven by in-situ generated oxyhydrogen

We present a novel method for shockwave-assisted bacterial transformation using a miniature oxyhydrogen detonation-driven shock tube. We have obtained transformation efficiencies of about 1.28 × 106, 1.7 × 106, 5 × 106, 1 × 105, 1 × 105 and 2 × 105 transformants/µg of DNA for Escherichia coli, Salmonella Typhimurum, Pseudomonas aeruginosa, Mycobacterium smegmatis, Mycobacterium tuberculosis (Mtb) and Helicobacter pylori respectively using this method which are significantly higher than those obtained using conventional methods. Mtb is the most difficult bacteria to be transformed and hence their genetic modification is hampered due to their poor transformation efficiency. Experimental results show that longer steady time duration of the shockwave results in higher transformation efficiencies. Measurements of Young’s modulus and rigidity of cell wall give a good understanding of the transformation mechanism and these results have been validated computationally. We describe the development of a novel shockwave device for efficient bacterial transformation in complex bacteria along with experimental evidence for understanding the transformation mechanism.

Corrigendum: Successful treatment of biofilm infections using shock waves combined with antibiotic therapy

This corrects the article DOI: 10.1038/srep17440.

Enhancing the efficiency of desensitizing agents with shockwave treatment – a new paradigm in dentinal hypersensitivity management

Dentine sensitivity, characterised by a sharp dental pain is experienced by the population globally. Desensitizing toothpastes are prescribed to treat dentine hypersensitivity. These agents occlude the exposed dentine tubules thereby reducing fluid movement although the effect is not long lived. We have developed a novel system which uses micro-shockwaves in combination with commercially available desensitizing toothpastes to efficiently treat hypersensitivity. This method of treating hypersensitivity strongly blocks dentinal tubules making it resistant to erosion even by acid challenge. We, thus, report a novel method to manage hypersensitivity using the most minimally invasive technique which is potentially translatable to clinics.

Biological Effects of Shock Waves on Infection

Shock waves have been successfully used for disintegrating kidney stones[1], noninvasive angiogenic approach[2] and for the treatment of osteoporosis[3]. Recently shock waves have been used to treat different medical conditions including intestinal anastomosis[4], wound healing[5], Kienbock’s disease[6] and articular cartilage defects[7].

Micro-shock Wave Assisted Plant Transformation

Genetically modified (GM) crops are developed by transforming the desired DNA to plant. There are various methods employed to achieve the required transformation in plants. Agrobacterium mediated transformation and Biolistics or particle bombardment method are the most commonly used methods.

Drag reduction by controlled base flow separation

THEproblem of wake .ow at high speeds and the drag associated with it are a signi.cant source of observation in the design of missiles, projectiles, and other typical high-speed vehicles. A large wake at the base of a vehicle would cause an increase in the overall drag due to the reduced base pressure. The wake studies of highspeed bodies also gain importance due to the severe aerodynamic heating problem and a high rise in the temperature of the base .ow. Many methods were devised to reduce the base drag of such highspeed bodies. These included boat tailing, base bleed, base combustion, locked vortex afterbodies, ventilated cavities, etc. Among these methods, the boat-tailed or conical afterbody concept was very popular and was found very effective in reducing base drag. But to achieve this drag reduction, the length of the conical/boattailed afterbody has to be suf.ciently large, terminating in a sharp trailing end. A short, conical/boat-tailed afterbody does not offer a suf.cient pressure recovery on its surface and, moreover, incurs considerable skin friction drag. On the other hand, using a short multistep afterbody that utilizes the concept of controlled .ow separation at the base of the vehicle can work out to be a better method of reducing base drag, provided a careful optimization of the con.guration geometry is carried out; thereby, permitting the use of shorter, lighter, and hence possibly lower cost afterbodies [1].