A Conceptual Review on Micro Bubbles
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2017, Vol 1, Issue 2
Abstract
Microbubbles system is a newly invented non-invasive technique in which, in the presence of ultrasound waves or harmonic sounds micropores shrinks and agitated to produce micro bubbles within the applied area. These bubbles have the capability to target any perfused tissues within our body. Recently it was postulated that due to its narrow size range (1 to 10μm vesicular diameter) it can get easily engulf by phagocytic blood cells which can be very effective on lymphocytic cancer. Micro bubbles are prepared by using mechanical agitation, ultrasonication, pressurized gas-liquid mixing system etc. Micro bubbles are made up of a monolayer of protein shells, lipid shells, surfactant shells, polymer shells, Polyelectrolyte multilayer shells. Initially, microbubbles are used as diagnostic tools but due to its versatility of uses and properties of surface conjugation of proteins, genes, micro molecular nutrients, drugs slowly it’s becoming a therapeutic delivery tool. ALBUNEX® (GE Healthcare) was the first albumin conjugated micro bubble which was been approved by US-FDA. Recently importance is been given for brain targeting using Micro bubble carrier system. It was observed that using passive and active transport micro streamed bubbles can able to transport through Blood Brain Barrier (BBB). It is very important to give more importance to its stability and canonization of globules for more industrial acceptability. Due to extensive research and accepting challenges of drug delivery in the brain by scientists, certain brain targeting approaches have been developed during recent times. Some of such approaches like; Osmatic and biochemical BBB dispersion, intra cerebral implants, intra ventricular incisions, BBB carrier mediated and active efflux transport (non-invasive), ligands and chemical peptide bindings, nanoparticular approaches, Trojan house approaches, intranasal drug delivery, using ultrasound webs targeting the brain cells, Avidin-Biotin Technology, genetically engineered molecular antibodies for human therapy, peptide radiopharmaceuticals, nonviral gene therapy has shown some good responses as far as brain drug delivery was concerned. In the recentera, nanoparticular approaches are dominating in research, but it was confirmed that reticule-endothelium system of the brain could not able to uptake nanoparticles during intravenous administration. Nanoparticles did not prove to be a successful approach for brain drug delivery system. Moreover, nanoparticlesovercoated with polysorbit-80 cause indeed some penetration towards the brain, but nanoparticles significance absorption was also been seen in spleen, bone marrow, lungs. Excessive usage of a surfactant such as polysorbit-80 also causes neuronal damage. Force ultrasound dispersion, a novel approach developed in recent times has its own capability to circumvent BBB and allows drug transport within the brain epithelial tissues. This non-invasive technique has its own advantages over chemically induced nano particle’s, because of its reversible nature. Hynynen has demonstrated that microbubbles intravenous injections with the help of Force Ultrasounds towards brain epithelial were more effective and rapid. Tran cranial application of ultrasound has been used for microbubble delivery of contrast agent as well as for delivery of drug molecules and gene as well. Paul Ehrlich was the one who identified the Blood Brain Barrier (BBB). He noticed during staining of in vitro circulatory system,almost all the organs were stained except spinal cord and brain. On this context, more eminent scientists like Max Lewandowsky, Edwin Goldman observed limited permeation of potassium ferrocyanate into the brain. On the other hand,goldmen, when injected trypan blue dye within the spinal cord, observed only brain cells gets stained. But all these research has not proven the existence of permissible barrier called BBB. During 1967 Davidson and Spaziani demonstrated that cerebral capillaries are responsible for prevention of diffusion of iodine, sucrose, and p-amino hippurate into the brain. Within the brain capillaries, it was observed that neuron is densely packed and perfused within its microvasculature. Actually, BBB comprising of endothelial cells, tight junctions, central nervous systems blood vesicles, basement membrane, astrocytes, and pericytes [1]. These layers actually acted as a front line defense system for brain and not allows toxic and endotoxins to penetrate inside of the brain. Tight junction assimilated with guanylate, occluding, cingulin, cadherins which are preventing circulating substance to penetrate brain through pure cellular routes. BBB is not allowing larger molecular weight constituents (>500Da), ionic and water-soluble substances to infiltrate inside of the brain. Hence, BBB hinders all macromolecular drugs, diagnostic substances, small molecular agents from penetrating the brain. These obstacles make CNS drug delivery more challenging [2-4]. Drug targeting to the brain is one of the burning questions within the scientific communities as so many CNS disorders and diseases can be wiping out by targeting brain cells. As far as the business point of view is concerned CNS-targeted drug delivery must get some sort of elevation to compete with the cardiovascular market. The major reason for not being given importance by investors in CNS drug targeting is because themajority of drugs are not crossing the BBB to deliver desirable results. Only a few lipid soluble drugs, less molecular weight drugs (<500 Da) can actually cross blood brain barrier. Even though, HIV, brain cancer, Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and childhood inborn genetic errors affecting the brain are not effectively can be treated by using conventional lipid soluble and low molecular weight drugs [5,6]. As far as Parkinson disease (PD) were concerned, L-dihydroxyphenylalanine (L-Dopa) treatment was available for several years, but no specific neuroprotective drugs are available to prevent inexorable neurodegradations caused by the PD.
Authors and Affiliations
Sankha Bhattacharya, Bhupendra Prajapati, Arindam A Paul
Keywords
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- EP ID EP567152
- DOI 10.26717/BJSTR.2017.01.000193
- Views 203
- Downloads 0
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