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Microorganism Powered Thermo-Pneumatic Pump | Drug delivery systems
Drug delivery is process of administering pharmaceutically active compound with a goal to produce therapeutic effect. Technology applied in drug delivery system development is important because it affects drug release and its absorption, distribution, metabolism and elimination from the body. Drug delivery needs to ensure safe application of the precise amount of drug and ensure that used method is convenient for the patient. Drug can be released by diffusion, degradation, and swelling or by affinity-based mechanisms. Most popular drug administration routes are oral (through the mouth), transdermal (through the skin), transmucosal (through nasal, sublingual, vaginal, rectal or through some other mucosa) or via inhalation.

After drug is ingested, it undergoes metabolic changes and its concentration in the body is dropping down. Conventional therapeutics contains larger doses of pharmaceutically active compound to ensure desired medical effect after metabolic degradation of the drug. High level of drug could impair a lot of other biochemical processes in the body and induce different kind of side effects. Some types of drugs (peptide and protein based drugs and different antibodies…) undergo fast enzymatic degradation when applied using conventional methods. Some other types of drugs are not suitable for the systemic circulation due to large molecular size. Targeted or smart drug delivery is relatively new field of medicine that is focused on systems that could deliver drug to a targeted tissue in amount that is medically essential. Using these systems, medicine can be delivered to specific location (certain tissue or group of cells) without damaging healthy (surrounding) tissue. Also, treatment duration can be regulated (prolonged) by specifically designed drug releasing methods.

To optimize drug delivery, team of scientists including chemists, biologists, doctors and engineers is needed. Drug vehicle needs to be non-toxic, non-mutagenic, biodegradable, biocompatible and non-immunogenic. Different types of drug vehicles are used today. Most famous are polymeric micelles, liposomes, lipoprotein-based drug carriers and nano-particle drug carriers.

Liposomes are most commonly used drug vehicles because they are biocompatible and biodegradable and don’t produce toxic or immunogenic response. They could be specifically designed to skip renal clearance and chemical or enzymatic inactivation. Main problem with liposomes is their high instability when applied in vitro and immediate reuptake and clearance by reticuloendothelial system when applied in vivo. Addition of PEG to the surface of the liposome prolongs their circulation time significantly.

Polymeric micelles are created using hydrophilic and hydrophobic monomer units. They are mostly used as vehicles for poorly soluble drugs.

Biodegradable particles are used in controlled release therapy. These particles are bearing ligands to P-selectin, E-selectin and ICAM-1 and successfully target inflamed endothelium.

Artificial DNA nanostructures are manufactured using DNA as structural and chemical material (not as a carrier of hereditary characteristics). Idea is to use DNA that will respond (release drug) when certain stimuli, such as specific mRNA, are applied.

Newly invented drug-delivery system is microorganism-powered thermo-pneumatic pump. All “equipment” is placed in a single patch. Drug is placed in the reservoir made of stacked layers of polydimethylsiloxane and a silicon substrate while baker's yeast and sugar are placed in a small working chamber. Before applying a patch to the skin, water needs to be added. Body heat will then trigger yeast fermentation resulting in small amount of carbon dioxide. Gas production is directly dependent upon time and temperature; created carbon dioxide pushes the membrane (thanks to ~5.86 kPa generated pressure) allowing drug pump to work continually for more than two hours. Autoimmune disorders and cancer treatment has been associated with large molecules that can’t penetrate the skin using traditional drug delivery patch. Invention of micro-needle transdermal patch partially solved the problem. Researchers believe that numerous drugs could be delivered transdermally using thermo-pneumatic patch able to generate necessary force to pump the drug and micro-needles that could penetrate cutaneous barrier. Besides being able to solve a problem associated with large molecules and inefficient transdermal application of some drugs, robustness of yeast would provide long shelf life for transdermal patches with thermo-pneumatic pump.

Targeted drug delivery has a lot of applications, mainly in cardiovascular and cancer therapy. Advantages of this kind of treatment are numerous. Future experiments in this field will probably increase the number of drug delivery systems and expand their application options.
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