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Lipid bilayer
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==Commercial applications== To date, the most successful commercial application of lipid bilayers has been the use of [[liposome]]s for drug delivery, especially for cancer treatment. (Note- the term “liposome” is in essence synonymous with “[[Vesicle (biology)|vesicle]]” except that vesicle is a general term for the structure whereas liposome refers to only artificial not natural vesicles) The basic idea of liposomal drug delivery is that the drug is encapsulated in solution inside the liposome then injected into the patient. These drug-loaded liposomes travel through the system until they bind at the target site and rupture, releasing the drug. In theory, liposomes should make an ideal drug delivery system since they can isolate nearly any hydrophilic drug, can be grafted with molecules to target specific tissues and can be relatively non-toxic since the body possesses biochemical pathways for [[Metabolize|degrading]] lipids.<ref name=Immordino2006>{{cite journal |vauthors=Immordino ML, Dosio F, Cattel L |title=Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential |journal=Int J Nanomed |volume=1 |issue=3 |pages=297–315 |year=2006 |pmid=17717971 |pmc=2426795 |doi=10.2217/17435889.1.3.297 }}</ref> The first generation of drug delivery liposomes had a simple lipid composition and suffered from several limitations. Circulation in the bloodstream was extremely limited due to both [[renal]] clearing and [[phagocytosis]]. Refinement of the lipid composition to tune fluidity, surface charge density, and surface hydration resulted in vesicles that adsorb fewer proteins from [[blood serum|serum]] and thus are less readily recognized by the [[immune system]].<ref name=Chonn1992>{{cite journal |vauthors=Chonn A, Semple SC, Cullis PR |title=Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes |journal=J. Biol. Chem. |volume=267 |issue=26 |pages=18759–65 |date=15 September 1992 |doi=10.1016/S0021-9258(19)37026-7 |pmid=1527006 |doi-access=free }}</ref> The most significant advance in this area was the grafting of [[polyethylene glycol]] (PEG) onto the liposome surface to produce “stealth” vesicles, which circulate over long times without immune or renal clearing.<ref name=Boris1997>{{cite journal |vauthors=Boris EH, Winterhalter M, Frederik PM, Vallner JJ, Lasic DD |title=Stealth liposomes: from theory to product |journal=Advanced Drug Delivery Reviews |volume=24 |issue= 2–3|pages=165–77 |year=1997 |doi=10.1016/S0169-409X(96)00456-5}}</ref> The first stealth liposomes were passively targeted at [[tumor]] tissues. Because tumors induce rapid and uncontrolled [[angiogenesis]] they are especially “leaky” and allow liposomes to exit the bloodstream at a much higher rate than normal tissue would.<ref name=Maeda2001>{{cite journal |vauthors=Maeda H, Sawa T, Konno T |title=Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS |journal=J Control Release |volume=74 |issue=1–3 |pages=47–61 |date=July 2001 |pmid=11489482 |doi=10.1016/S0168-3659(01)00309-1}}</ref> More recently{{when|date=January 2011}} work has been undertaken to graft [[antibodies]] or other molecular markers onto the liposome surface in the hope of actively binding them to a specific cell or tissue type.<ref name=Lopes1999>{{cite journal |vauthors=Lopes DE, Menezes DE, Kirchmeier MJ, Gagne JF |title=Cellular trafficking and cytotoxicity of anti-CD19-targeted liposomal doxorubicin in B lymphoma cells |journal=Journal of Liposome Research |volume=9 |issue= 2|pages=199–228 |year=1999 |doi=10.3109/08982109909024786}}</ref> Some examples of this approach are already in clinical trials.<ref name=Matsumura2004>{{cite journal |vauthors=Matsumura Y, Gotoh M, Muro K, etal |title=Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer |journal=Ann. Oncol. |volume=15 |issue=3 |pages=517–25 |date=March 2004 |pmid=14998859 |doi=10.1093/annonc/mdh092|doi-access=free }}</ref> Another potential application of lipid bilayers is the field of [[biosensor]]s. Since the lipid bilayer is the barrier between the interior and exterior of the cell, it is also the site of extensive signal transduction. Researchers over the years have tried to harness this potential to develop a bilayer-based device for clinical diagnosis or bioterrorism detection. Progress has been slow in this area and, although a few companies have developed automated lipid-based detection systems, they are still targeted at the research community. These include Biacore (now GE Healthcare Life Sciences), which offers a disposable chip for utilizing lipid bilayers in studies of binding kinetics<ref name="Biacore">[http://www.gelifesciences.com/biacore]{{Dead link|date=November 2023 |bot=InternetArchiveBot |fix-attempted=yes }}. Biacore Inc. Retrieved Feb 12, 2009.</ref> and Nanion Inc., which has developed an [[Planar patch clamp|automated patch clamping]] system.<ref>[http://www.nanion.de/pdf/PlanarPatchClamping.pdf Nanion Technologies. Automated Patch Clamp] {{Webarchive|url=https://web.archive.org/web/20100331130708/http://www.nanion.de/pdf/PlanarPatchClamping.pdf |date=31 March 2010 }}. Retrieved Feb 28, 2010. (PDF)</ref> A supported lipid bilayer (SLB) as described above has achieved commercial success as a screening technique to measure the permeability of drugs. This parallel artificial membrane permeability assay ([[PAMPA]]) technique measures the permeability across specifically formulated lipid cocktail(s) found to be highly correlated with [[Caco-2]] cultures,<ref>{{cite journal |pmid=14998573 |year=2004 |last1=Bermejo |first1=M. |title=PAMPA--a drug absorption in vitro model 7. Comparing rat in situ, Caco-2, and PAMPA permeability of fluoroquinolones |journal=European Journal of Pharmaceutical Sciences |volume=21 |issue=4 |pages=429–41 |last2=Avdeef |first2=A. |last3=Ruiz |first3=A. |last4=Nalda |first4=R. |last5=Ruell |first5=J. A. |last6=Tsinman |first6=O. |last7=González |first7=I. |last8=Fernández |first8=C. |last9=Sánchez |first9=G. |last10=Garrigues |first10=T. M. |last11=Merino |first11=V. |doi=10.1016/j.ejps.2003.10.009}}</ref><ref>{{cite journal |pmid=15734300 |year=2005 |last1=Avdeef |first1=A. |title=Caco-2 permeability of weakly basic drugs predicted with the double-sink PAMPA pKa(flux) method |journal=European Journal of Pharmaceutical Sciences |volume=24 |issue=4 |pages=333–49 |last2=Artursson |first2=P. |last3=Neuhoff |first3=S. |last4=Lazorova |first4=L. |last5=Gråsjö |first5=J. |last6=Tavelin |first6=S. |doi=10.1016/j.ejps.2004.11.011}}</ref> the [[gastrointestinal tract]],<ref>{{cite journal |pmid=15265506 |year=2004 |last1=Avdeef |first1=A. |title=PAMPA--a drug absorption in vitro model 11. Matching the in vivo unstirred water layer thickness by individual-well stirring in microtitre plates |journal=European Journal of Pharmaceutical Sciences |volume=22 |issue=5 |pages=365–74 |last2=Nielsen |first2=P. E. |last3=Tsinman |first3=O. |doi=10.1016/j.ejps.2004.04.009}}</ref> [[blood–brain barrier]]<ref>{{cite journal |pmid=19591928 |pmc=2747801 |year=2009 |last1=Dagenais |first1=C. |title=P-glycoprotein deficient mouse in situ blood-brain barrier permeability and its prediction using an in combo PAMPA model |journal=European Journal of Pharmaceutical Sciences |volume=38 |issue=2 |pages=121–37 |last2=Avdeef |first2=A. |last3=Tsinman |first3=O. |last4=Dudley |first4=A. |last5=Beliveau |first5=R. |doi=10.1016/j.ejps.2009.06.009}}</ref> and skin.<ref>{{cite journal |pmid=19937821 |year=2009 |last1=Sinkó |first1=B. |title=A PAMPA study of the permeability-enhancing effect of new ceramide analogues |journal=Chemistry & Biodiversity |volume=6 |issue=11 |pages=1867–74 |last2=Kökösi |first2=J. |last3=Avdeef |first3=A. |last4=Takács-Novák |first4=K. |doi=10.1002/cbdv.200900149 |s2cid=27395246}}</ref>
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