from ref with permission concentration of drug fig tissue burden for mice infected in a model of invasive aspergillosis after oral administration of camb from ref with permission lisinopril-hctz 10-12.5 mg lup the tissue fungal burden for target organs, kidneys, liver and lungs, demonstrated the benefic effect of camb fig camb showed a pronounced dose dependent reduction in the fungal burden in lisinopril-hctz 10-12.5 mg lup al organs the near eradication of aspergillus was observed above a concentration of mgkgday camb at mgkg po was as effective as camb at mgkg po in reducing fungal tissue lisinopril-hctz 10-12.5 mg lup burden in cryptococcal meningitis animal model oral amphotericin � cochleates were effective in a murine cryptococcal meningitis model with an survival after days, obtained after oral treatment with camb lomgkg to mice having intracerebral infection with cryptococcus neoformans toxicity of amphotericin � cochleates in vitro, amphotericin � cochleates camb showed a low toxicity on red blood cells when compared with fungizone damb camb showed no hemoglobin release and therefore no hemolysis of red blood cells when incubated at igml in contrast, damb was hemolytic at xgml due to the presence of the detergent, sodium desoxycholate in vivo, camb was non toxic to mice when administered orally at mgkgday for days no nephrotoxicity was observed as demonstrated by the normal bun lisinopril-hctz 10-12.5 mg lup level, and the histopathology of kidneys, lungs, liver, spleen and gi tract showed that animals dosed with camb were comparable to controls pharmacokinetics of amphotericin � cochleates oral pharmacokineticspt pharmacokinetic lisinopril-hctz 10-12.5 mg lup studies have shown that after oral administration of camb, amb is distributed into the target tissues eg brain, liver, lung, spleen and kidneys in healthy mice and amb tissue level lisinopril-hctz 10-12.5 mg lup suggests a zeroorder uptake process for all tissues when camb was administered po to cbl mice at lomgkg � = , and blood and tissues collected and amb level measured by lisinopril-hctz 10-12.5 mg lup hplc, blood shows a plateaushaped profile with tmax = h and cmax = mgml non compartmental nca analysis showed blood aucoo = xghml, ti = h, mrto�� = h, clf = mlminkg, vzf = lkg amb tissue exposure auco��, mghg evaluated using nca was greater for lungs , followed by liver , spleen kidneys and heart tissue elu tion tih kidneys , lungs , lisinopril-hctz 10-12.5 mg lup heart , liver and spleen for all tissues, tmax = h and cmax ranged between xgml for heart and igml for lungs the delivery of amb by cochleates after multiple oral lisinopril-hctz 10-12.5 mg lup doses was assessed in the same mouse model and was compared with ambisome it was found that cochleate provides therapeutic levels in tissue and presents better delivery and transfer efficiency of amb to the target tissue, as well as better tissue penetration the ability of cochleate vehicles to deliver systemic amb after single or multiple oral dosing suggest the lisinopril-hctz 10-12.5 mg lup potential of camb formulations to treat and prevent systemic fungal infections pharmacokinetics amb given intraveneously iv to mice showed a twophase pharmacokinetic profile, pharmacokinetic analysis in target tissues liver, spleen, lisinopril-hctz 10-12.5 mg lup kidney and lungs shows a multipeak profile, large auc and mrt after iv administration of mgkg, amb presented a twophase blood concentration time course [fig a] this profile is characterized lisinopril-hctz 10-12.5 mg lup by a very fast distribution phase and an elimination phase with t = hrs the auco�� was a,ghml, ci = mlminkg, mrtoo = hrs and vss = lkg this lisinopril-hctz 10-12.5 mg lup pharmacokinetic profile indicates that camb is removed fast from blood in addition, the large vss also indicates a large distribution into the tissues the results obtained in target tissues showed lisinopril-hctz 10-12.5 mg lup this extensive distribution and penetration [fig b] calculation of pharmacokinetic parameters showed that the main target tissues have a large amb exposure reflected in the auc and cmax values table , lisinopril-hctz 10-12.5 mg lup as well as the tissue to blood auc ratio the large amb exposure in liver and spleen suggests involvement of the mononuclear phagocyte system mps in the removal of camb lisinopril-hctz 10-12.5 mg lup cochleates are particulates that can be quickly cleared from the circulation by the macrophages of the reticular endothelial system res related to the liver and the spleen in addition, physical lisinopril-hctz 10-12.5 mg lup retention seems to play a role in the kinetic profile of the lungs due to its capillary nature time hours fig a amb profile in blood after a single dose lisinopril-hctz 10-12.5 mg lup � iv pk profile of amb in target tissues, from ref , with permission table pharmacokinetics parameters for camb in different target organs after iv administration to cbl mice n = lisinopril-hctz 10-12.5 mg lup per time point from ref , with permission tissue auc t ma � max zv mgh min mgg hrs liver spleen lung kidney heart intestine stomach this phenomenon and the mobility lisinopril-hctz 10-12.5 mg lup of the macrophages seem to cause certain redistribution of cochleates that gives a multipeak and plateau shape profiles in liver and spleen finally, amb was also detected in bile and lisinopril-hctz 10-12.5 mg lup intestine contents, suggesting that bile excretion may be an additional elimination route , other potential applications for cochleates cochleate for the delivery of antibiotics as cochleate has shown a high affinity lisinopril-hctz 10-12.5 mg lup to be engulfed by macrophages [fig a] probably due to a dual mechanism, the cochleate essential particulate feature and possibly a ps receptor mediated internalization of the cochleate into macrophage lisinopril-hctz 10-12.5 mg lup putfl� fig uptake of amphotericin � cochleates by j macrophages as seen by a fluorescence microscopy, b confocal microscopy from ref , with permission this particulate system would have potential lisinopril-hctz 10-12.5 mg lup for the delivery of antibacterial agents such as aminoglycosides and vancomycin illustration is given by the encapsulation of clofazimine, an antitb drug, and tobramycin, an aminoglycoside antibiotic used in treating lisinopril-hctz 10-12.5 mg lup bacterial infections, both given intraveneously thus far the cochleate system may possibly offer a new oral way of delivery delivery of clofazimine clofazimine cochleates were prepared by the trapping method lisinopril-hctz 10-12.5 mg lup clofazimine is a known hydrophobic antitb drug, the efficacy of clofazimine cochleate was assessed by measuring the ic in vero cells and in bone marrow derived macrophage bmm clofazimine cochleates lisinopril-hctz 10-12.5 mg lup exhibit a greater decrease in toxicity versus free clofazimine and had a higher efficacy in killing intracellular m tuberculosis than free clofazimine log reduction ce was achieved at igml for cochleates, while free clofazimine was toxic at this concentration this shows that encapsulation of clofazimine in cochleates potentiates the antimicrobial efficacy of the drug, ie when higher concentration of drug lisinopril-hctz 10-12.5 mg lup can be used because of less toxicity, bactericidal levels of the drug could be attained delivery of tobramycin a recent research work has been published on the possible use of lisinopril-hctz 10-12.5 mg lup nanocochleates as an oral delivery system for tobramycin tobramycin is a well known aminoglycoside antibiotic used in treating bacterial infections, and is usually administered by intravenous iv infusion, intramuscular im lisinopril-hctz 10-12.5 mg lup injection, or inhalation this amin ogycoside drug is known for its side effects such as mineral depletion ie calcium, magnesium, potassium after iv administration in this work, the author described lisinopril-hctz 10-12.5 mg lup that tobramycin which is positively charged at low ph, will be encapsulated in the interbilayer space of cochleates the fusion of unilamellar liposomes is no longer induced by a metal lisinopril-hctz 10-12.5 mg lup cation such as ca, but by the organic molecule to be encapsulated the cochleate cylinders formation has been described by papahadjoupolos as resulting partly from the intrinsic properties of the lisinopril-hctz 10-12.5 mg lup calcium cation indeed, phosphatidylserine shows considerable selectivity for calcium due to the propensity of calcium to lose part of its hydration shell, and to displace water upon complex formation in lisinopril-hctz 10-12.5 mg lup the cochleate solid crystalline structures formation, calcium plays a crucial role in bringing bilayers together closely through partial dehydration of the membrane surface and the cross linking of opposing molecules lisinopril-hctz 10-12.5 mg lup of phosphatidylserine in our opinion, in this recent work where formation of cochleate is claimed with no calcium present, additional relevant physicochemical evidence on cochleate formation and the localization of lisinopril-hctz 10-12.5 mg lup the drug in the interbilayer space will be needed cochleate for the delivery of antiinflammatory drugs as a result of the deep embedding of the molecules in the cochleates structures, drug molecules are hidden from the outside environment this should have two beneficial effects one is to hide and protect the molecule from the degradation due to environment the other is to protect, the environment when needed, from the active molecule when such molecule presents side effects this is the case of antiinflammatory drugs, which associates cure to the lisinopril-hctz 10-12.5 mg lup disturbance of gi tract stomach for instance cochleates were described to act beneficially in this area, reducing the stomach irritation when antiinflammatory drugs such as aspirin is hidden in the lisinopril-hctz 10-12.5 mg lup cochleate structure, and administered to a car rageenan rat model for acute inflammation other uses of cochlea tes cochleates were also described as vehicles for nutrients as an improved drug lisinopril-hctz 10-12.5 mg lup and contrast agent delivery system, as well as intermediate in the preparation of special liposomes such as large unilamellar vesicles luv and proteoliposomes in fact, the discovery of the cochleate lisinopril-hctz 10-12.5 mg lup structures was a result of the desire to prepare luv by pr papahadjoupoulos which were developed for the delivery of hydrophilic drugs proteoliposomes prepared from cochleates intermediates were described for vaccine applications in general, and more recently, when containing lipopolysaccharide as a novel adjuvant conclusion cochleates lipidbased nanocarrier appears to have potential for the oral delivery of bioactive molecules future lisinopril-hctz 10-12.5 mg lup work should be directed towards more fundamental science, as many research aspects of the cochleate drug carrier system are still hardly known eg localization of the drug in lipid bilayers, lisinopril-hctz 10-12.5 mg lup impact of multivalent cations on the cochleate formation, mechanism of action of cochleate after oral uptake in addition, the development of friendly analytical assays to monitor the drug localization and loading percentage in cochleates will be desired this nano drug carrier is currently under development by biodelivery sciences international having the first drugcochleate in the market place represents a big lisinopril-hctz 10-12.5 mg lup challenge for instance, when oral amphotericin � cochleates are ultimately available for patients, thus will provide a new opening in the treatment of systemic fungal infections references chien yw novel drug delivery systems drugs and the pharmaceutical sciences, vol marcel dekker new york, ny rathbone mj, hadgraft j and michael sr modifiedrelease drug delivery technology drugs and the pharmaceutical sciences, lisinopril-hctz 10-12.5 mg lup vol marcel dekker new york, ny charman wn lipids, lipophilic drugs and oral deliverysome emerging concepts j pharm sci bowtle w lipid formulations for oral drug delivery pharm technol eur attwood d microemulsions, in kreutrer j ed colloidal drug delivery systems marcel dekker new york, pp lawrence mj microemulsions as drug delivery vehicles curr opin colloid interface sci pouton cw lisinopril-hctz 10-12.5 mg lup and charman wn the potential of oily formulations for drug delivery to the gastrointestinal tract adv drug del rev muller rh, mader � and gohla s solid lipid nanoparticles lisinopril-hctz 10-12.5 mg lup sln for controlled drug delivery a review of the state of the art eur j pharm biopharm westesen � novel lipidbased colloidal dispersions as potential drug administration systems, expectations and lisinopril-hctz 10-12.5 mg lup reality colloid polym sci lamprecht a, bouligand y and benoit jp new lipid nanocapsules exhibit sustained release properties for amiodarone ] control rel lamprecht a, saumet jl, roux j and lisinopril-hctz 10-12.5 mg lup benoit jp lipid nanocarriers as drug delivery systems for ibuprofen in pain treatment intl} pharm razzaque ms, koji t, kumatori a and tagushi t cisplatininduced apoptosis in human proximal tubular lisinopril-hctz 10-12.5 mg lup epithelial cells is associated with the activation of the fasfas ligand system histochem cell biol razzaque ms, hossain ma, ahsan n and tagushi t lipid formulations of polyene antifungal drugs lisinopril-hctz 10-12.5 mg lup and attenuation of associated nephrotoxicity nephron hossain ma, maesaki s, kakeya h, noda t, yanagihara k, sasaki e, hirakata y, tomono k, tashiro t and kohno s efficacy of ns, lisinopril-hctz 10-12.5 mg lup a novel lipid nanosphere encapsulated amphotericin b, against cryptococcus neoformans antimicrob agents chemother otsubo t, maesaki s, yamamoto y, tomono k, tashiro t, seki j, tomii y, sonoke s and lisinopril-hctz 10-12.5 mg lup kohno s in vitro and in vivo activities of ns, a new lipid nanosphere incorporating amphotericin b, against aspergillus fumigatus antimicrob agents chemother trotta m, cavalli r, carlotti me, battaglia lisinopril-hctz 10-12.5 mg lup l and debernardi f solid lipid microparticles carrying insulin formed by solventinwater emulsiondiffusion technique int f pharm zarif l elongated supramolecular assemblies in drug delivery j control rel rev zarif lisinopril-hctz 10-12.5 mg lup l, graybill jr, perlin d and mannino rj cochleates new lipidbased drug delivery system ] liposome res papahadjopoulos d, vail wj, jacobson � and poste g cochleate lipid cylinders formation lisinopril-hctz 10-12.5 mg lup by fusion of unilamellar lipid vesicles bioehim biophys acta papahadjopoulos d large unilamellar vesicles luv and method of preparing the same us patent papahadjopoulos d, nir s and duzgunes n lisinopril-hctz 10-12.5 mg lup molecular mechanisms of calcium induced membrane fusion j bioenerg biomembr wilschut j and papahadjopoulos d ca induced fusion of phospholipid vesicles monitored by mixing of aqueous contents nature mannino rj lisinopril-hctz 10-12.5 mg lup and gouldfogerite s antigen cochleate formulations for oral and systemic vaccination, in levine mm ed new generation vaccines marcel dekker new york, pp zarif l and perlin d amphotericin � lisinopril-hctz 10-12.5 mg lup nanocochleates from formulation to oral efficacy drug del technol zarif l, graybill jr, perlin d, navjar l, bocanegra r and mannino rj antifungal activity of amphotericin � cochleates against candida lisinopril-hctz 10-12.5 mg lup albicans in a mouse model antimi crob agents chemother walsh tj, viviani ma, arathoon e, chiou c, ghannoum m, groll ah and odds fc new targets and delivery systems lisinopril-hctz 10-12.5 mg lup for antifungal therapy medmycol supp l biodelivery sertraline hcl prescription assistance program sciences wwwbiodeliverysciencescom unger e method for delivering bioactive agents using cochleates us b zarif l, jin t, segarra i and mannino rj new lisinopril-hctz 10-12.5 mg lup cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules pct application wool a zarif l and mannino rj cochleates lipidbased vehicles for gene delivery lisinopril-hctz 10-12.5 mg lup concept, achievements and future development, in habib n ed cancer gene therapy past achievements and future challenges kluwer academicplenum publishers new york, pp graham i, gagne j and silvius jr lisinopril-hctz 10-12.5 mg lup kinetics and thermodynamics of calcium induced lateral phase separations in phosphatidic acid containing bilayers biochemistry archibald dd and mann s selfassembled microstructures from ,ethanediol suspensions of pure and binary mixtures lisinopril-hctz 10-12.5 mg lup of neutral and acidic biological galactosylce ramides chem phys lipids l holland jw, hui c, cullis pr and madden td polyethylene glycollipid conjugates regulate the calciuminduced fusion of liposomes composed lisinopril-hctz 10-12.5 mg lup of phos phatidylethanolamine and phosphatidylserine biochemistry villardita c, grioli s, salmeri g, nicoletti f and pennisi g multicenter clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration, clin lisinopril-hctz 10-12.5 mg lup trials ] crook th, tinklenberg j, yesavage j, petrie w, nunzi mg and massari dc effects of phosphatidylserine in ageassociated memory impairment neurology engle rr, satzger w and gunther w lisinopril-hctz 10-12.5 mg lup doubleblind crossover study of phosphatidylserine vs placebo in patients with early dementia of the alzheimer type eur neuropsychopharmacol amaducci l phosphatidylserine in the treatment of alzheimers disease results of a multicenter study psychopharmacol bull cennachi t, bertoldin t, farina c, fiori mg and crepaldi g cognitive decline in the elderly a double blind, placebocontrolled multicenter study on efficacy of phosphatidylserine lisinopril-hctz 10-12.5 mg lup administration aging guidin j et al effect of soy lecithin phosphatidylserine ps complex on memory impairment and mood in the functioning elderly dept geriatrics, kaplan hospital, rehovot, israel maggioni m, lisinopril-hctz 10-12.5 mg lup picotti gb, bondiolotti gp et al effects of phosphatidylserine therapy in geriatric patients with depressive disorders acta psychiatr scand nerozzi d, aceti f, melia e, magnani a, marino r, genovesi lisinopril-hctz 10-12.5 mg lup g, amalfitano m, cozza g, murgiano s, de giorgis g, et al phosphatidylserine and memory disorders in the aged clin per monteleone p, beinat l, tanzillo c, maj m and lisinopril-hctz 10-12.5 mg lup kemali d effects of phosphatidylserine on the neuroendocrine response to physical stress in humans neuroen docrinology monteleone p et al blunting by chronic phosphatidylserine administration of the stressinduced activation of lisinopril-hctz 10-12.5 mg lup the hypothalamopituitaryadrenal axis in healthy men eur ] clin pharmacol funfgeld ew, baggen m, nedwidek p, richstein � and mistlberger g double blind study with phosphatidylserine ps in parkinsonian lisinopril-hctz 10-12.5 mg lup patients with senile dementia of alzheimers type sdat prog clin res zarif l and tan f cochleates made with purified soy phosphatidylserine us al duzgunes n, nir s, wischut j, lisinopril-hctz 10-12.5 mg lup bentz j, newton c, portis a and papahadjopoulos d calcium and magnesium induced fusion of mixed phosphatidylserine phosphatidylcholine vesicles effect of ionbinding j membr biol portis a, newton c, pangborn lisinopril-hctz 10-12.5 mg lup w and papahadjopoulos d studies on the mechanism of membrane fusion evidence for an intermembrane caphospholipid complex, synergism with mg, and inhibition by spectrin biochemistry santangelo r, paderu p, delmas lisinopril-hctz 10-12.5 mg lup g, chen zw mannino r, zarif l and perlin d efficacy of oral cochleates amphotericin b in a mouse model of systemic candidiasis antimicrob agents chemother zarif l, segarra i, jin t, scolpino a, hyra d, daublin p, krause s, perlin ds, lambros c, graybill jr and mannino rj lipidbased cochleate system for oral and systemic delivery of drugs aaps lisinopril-hctz 10-12.5 mg mylan dist omeprazole cap 20 mg lup eastern regional meeting and exposition segarra i, hyramovshin da, chen zw, santangelo r, perlin d, paderu p, mannino rj and zarif l amb cochleates, a new lipidbased formulation for amphotericin b from iv pharmacokinetics to oral efficacy millenial world congress of pharmaceutical sciences, san franscisco, ca, april, pp segarra i, jin t, hyra d, mannino rj and zarif l oral administration of amphotericin � with a new ambcochleate formulation tissue distribution after single and multiple oral dose icaac abs segarra i, movshin d, mannino rj and zarif l pharmacokinetics and tissue distribution of amphotericin � in mice after oral administration of amb cochleates, a new effective lipidbased formulation for the oral treatment of systemic fungal infections icaac abs segarra i, lisinopril-hctz 10-12.5 mg lup chen zw, movshin da, tan f, mannino rj and zarif l tissue distribution of oral amphotericin � lipidbased cochleate formulation comparison with ambisome th international symposium on controlled release of lisinopril-hctz 10-12.5 mg lup bioactive materials, paris france, pp zarif l, segarra i, jin t, hyra d and mannino rj amphotericin � cochleates as a novel oral delivery system for the treatment of fungal infections th international symposium on controlled release of bioactive materials boston, ma, june perlin d, santangelo r, mannino r and zarif l oral delivery of cochleates containing amphotericin � camb lisinopril-hctz 10-12.5 mg lup is highly effective in a candidiasis murine model, focus fungal infect zarif l, segarra i, jin t, hyra d, perlin d, graybill jr and mannino jr oral and systemic delivery lisinopril-hctz 10-12.5 mg lup of amphotericin � mediated by cochleates aaps annual meeting and exposition, november zarif l, jin t, scolpino a and mannino rj are cochleates the new lipidbased carrier for oral drug delivery?
from ref with permission concentration of drug fig tissue burden for mice infected in a model of invasive aspergillosis after oral administration of camb from ref with permission lisinopril-hctz 10-12.5 mg lup the tissue fungal burden for target organs, kidneys, liver and lungs, demonstrated the benefic effect of camb fig camb showed a pronounced dose dependent reduction in the fungal burden in lisinopril-hctz 10-12.5 mg lup al organs the near eradication of aspergillus was observed above a concentration of mgkgday camb at mgkg po was as effective as camb at mgkg po in reducing fungal tissue lisinopril-hctz 10-12.5 mg lup burden in cryptococcal meningitis animal model oral amphotericin � cochleates were effective in a murine cryptococcal meningitis model with an survival after days, obtained after oral treatment with camb lomgkg to mice having intracerebral infection with cryptococcus neoformans toxicity of amphotericin � cochleates in vitro, amphotericin � cochleates camb showed a low toxicity on red blood cells when compared with fungizone damb camb showed no hemoglobin release and therefore no hemolysis of red blood cells when incubated at igml in contrast, damb was hemolytic at xgml due to the presence of the detergent, sodium desoxycholate in vivo, camb was non toxic to mice when administered orally at mgkgday for days no nephrotoxicity was observed as demonstrated by the normal bun lisinopril-hctz 10-12.5 mg lup level, and the histopathology of kidneys, lungs, liver, spleen and gi tract showed that animals dosed with camb were comparable to controls pharmacokinetics of amphotericin � cochleates oral pharmacokineticspt pharmacokinetic lisinopril-hctz 10-12.5 mg lup studies have shown that after oral administration of camb, amb is distributed into the target tissues eg brain, liver, lung, spleen and kidneys in healthy mice and amb tissue level lisinopril-hctz 10-12.5 mg lup suggests a zeroorder uptake process for all tissues when camb was administered po to cbl mice at lomgkg � = , and blood and tissues collected and amb level measured by lisinopril-hctz 10-12.5 mg lup hplc, blood shows a plateaushaped profile with tmax = h and cmax = mgml non compartmental nca analysis showed blood aucoo = xghml, ti = h, mrto�� = h, clf = mlminkg, vzf = lkg amb tissue exposure auco��, mghg evaluated using nca was greater for lungs , followed by liver , spleen kidneys and heart tissue elu tion tih kidneys , lungs , lisinopril-hctz 10-12.5 mg lup heart , liver and spleen for all tissues, tmax = h and cmax ranged between xgml for heart and igml for lungs the delivery of amb by cochleates after multiple oral lisinopril-hctz 10-12.5 mg lup doses was assessed in the same mouse model and was compared with ambisome it was found that cochleate provides therapeutic levels in tissue and presents better delivery and transfer efficiency of amb to the target tissue, as well as better tissue penetration the ability of cochleate vehicles to deliver systemic amb after single or multiple oral dosing suggest the lisinopril-hctz 10-12.5 mg lup potential of camb formulations to treat and prevent systemic fungal infections pharmacokinetics amb given intraveneously iv to mice showed a twophase pharmacokinetic profile, pharmacokinetic analysis in target tissues liver, spleen, lisinopril-hctz 10-12.5 mg lup kidney and lungs shows a multipeak profile, large auc and mrt after iv administration of mgkg, amb presented a twophase blood concentration time course [fig a] this profile is characterized lisinopril-hctz 10-12.5 mg lup by a very fast distribution phase and an elimination phase with t = hrs the auco�� was a,ghml, ci = mlminkg, mrtoo = hrs and vss = lkg this lisinopril-hctz 10-12.5 mg lup pharmacokinetic profile indicates that camb is removed fast from blood in addition, the large vss also indicates a large distribution into the tissues the results obtained in target tissues showed lisinopril-hctz 10-12.5 mg lup this extensive distribution and penetration [fig b] calculation of pharmacokinetic parameters showed that the main target tissues have a large amb exposure reflected in the auc and cmax values table , lisinopril-hctz 10-12.5 mg lup as well as the tissue to blood auc ratio the large amb exposure in liver and spleen suggests involvement of the mononuclear phagocyte system mps in the removal of camb lisinopril-hctz 10-12.5 mg lup cochleates are particulates that can be quickly cleared from the circulation by the macrophages of the reticular endothelial system res related to the liver and the spleen in addition, physical lisinopril-hctz 10-12.5 mg lup retention seems to play a role in the kinetic profile of the lungs due to its capillary nature time hours fig a amb profile in blood after a single dose lisinopril-hctz 10-12.5 mg lup � iv pk profile of amb in target tissues, from ref , with permission table pharmacokinetics parameters for camb in different target organs after iv administration to cbl mice n = lisinopril-hctz 10-12.5 mg lup per time point from ref , with permission tissue auc t ma � max zv mgh min mgg hrs liver spleen lung kidney heart intestine stomach this phenomenon and the mobility lisinopril-hctz 10-12.5 mg lup of the macrophages seem to cause certain redistribution of cochleates that gives a multipeak and plateau shape profiles in liver and spleen finally, amb was also detected in bile and lisinopril-hctz 10-12.5 mg lup intestine contents, suggesting that bile excretion may be an additional elimination route , other potential applications for cochleates cochleate for the delivery of antibiotics as cochleate has shown a high affinity lisinopril-hctz 10-12.5 mg lup to be engulfed by macrophages [fig a] probably due to a dual mechanism, the cochleate essential particulate feature and possibly a ps receptor mediated internalization of the cochleate into macrophage lisinopril-hctz 10-12.5 mg lup putfl� fig uptake of amphotericin � cochleates by j macrophages as seen by a fluorescence microscopy, b confocal microscopy from ref , with permission this particulate system would have potential lisinopril-hctz 10-12.5 mg lup for the delivery of antibacterial agents such as aminoglycosides and vancomycin illustration is given by the encapsulation of clofazimine, an antitb drug, and tobramycin, an aminoglycoside antibiotic used in treating lisinopril-hctz 10-12.5 mg lup bacterial infections, both given intraveneously thus far the cochleate system may possibly offer a new oral way of delivery delivery of clofazimine clofazimine cochleates were prepared by the trapping method lisinopril-hctz 10-12.5 mg lup clofazimine is a known hydrophobic antitb drug, the efficacy of clofazimine cochleate was assessed by measuring the ic in vero cells and in bone marrow derived macrophage bmm clofazimine cochleates lisinopril-hctz 10-12.5 mg lup exhibit a greater decrease in toxicity versus free clofazimine and had a higher efficacy in killing intracellular m tuberculosis than free clofazimine log reduction ce was achieved at igml for cochleates, while free clofazimine was toxic at this concentration this shows that encapsulation of clofazimine in cochleates potentiates the antimicrobial efficacy of the drug, ie when higher concentration of drug lisinopril-hctz 10-12.5 mg lup can be used because of less toxicity, bactericidal levels of the drug could be attained delivery of tobramycin a recent research work has been published on the possible use of lisinopril-hctz 10-12.5 mg lup nanocochleates as an oral delivery system for tobramycin tobramycin is a well known aminoglycoside antibiotic used in treating bacterial infections, and is usually administered by intravenous iv infusion, intramuscular im lisinopril-hctz 10-12.5 mg lup injection, or inhalation this amin ogycoside drug is known for its side effects such as mineral depletion ie calcium, magnesium, potassium after iv administration in this work, the author described lisinopril-hctz 10-12.5 mg lup that tobramycin which is positively charged at low ph, will be encapsulated in the interbilayer space of cochleates the fusion of unilamellar liposomes is no longer induced by a metal lisinopril-hctz 10-12.5 mg lup cation such as ca, but by the organic molecule to be encapsulated the cochleate cylinders formation has been described by papahadjoupolos as resulting partly from the intrinsic properties of the lisinopril-hctz 10-12.5 mg lup calcium cation indeed, phosphatidylserine shows considerable selectivity for calcium due to the propensity of calcium to lose part of its hydration shell, and to displace water upon complex formation in lisinopril-hctz 10-12.5 mg lup the cochleate solid crystalline structures formation, calcium plays a crucial role in bringing bilayers together closely through partial dehydration of the membrane surface and the cross linking of opposing molecules lisinopril-hctz 10-12.5 mg lup of phosphatidylserine in our opinion, in this recent work where formation of cochleate is claimed with no calcium present, additional relevant physicochemical evidence on cochleate formation and the localization of lisinopril-hctz 10-12.5 mg lup the drug in the interbilayer space will be needed cochleate for the delivery of antiinflammatory drugs as a result of the deep embedding of the molecules in the cochleates structures, drug molecules are hidden from the outside environment this should have two beneficial effects one is to hide and protect the molecule from the degradation due to environment the other is to protect, the environment when needed, from the active molecule when such molecule presents side effects this is the case of antiinflammatory drugs, which associates cure to the lisinopril-hctz 10-12.5 mg lup disturbance of gi tract stomach for instance cochleates were described to act beneficially in this area, reducing the stomach irritation when antiinflammatory drugs such as aspirin is hidden in the lisinopril-hctz 10-12.5 mg lup cochleate structure, and administered to a car rageenan rat model for acute inflammation other uses of cochlea tes cochleates were also described as vehicles for nutrients as an improved drug lisinopril-hctz 10-12.5 mg lup and contrast agent delivery system, as well as intermediate in the preparation of special liposomes such as large unilamellar vesicles luv and proteoliposomes in fact, the discovery of the cochleate lisinopril-hctz 10-12.5 mg lup structures was a result of the desire to prepare luv by pr papahadjoupoulos which were developed for the delivery of hydrophilic drugs proteoliposomes prepared from cochleates intermediates were described for vaccine applications in general, and more recently, when containing lipopolysaccharide as a novel adjuvant conclusion cochleates lipidbased nanocarrier appears to have potential for the oral delivery of bioactive molecules future lisinopril-hctz 10-12.5 mg lup work should be directed towards more fundamental science, as many research aspects of the cochleate drug carrier system are still hardly known eg localization of the drug in lipid bilayers, lisinopril-hctz 10-12.5 mg lup impact of multivalent cations on the cochleate formation, mechanism of action of cochleate after oral uptake in addition, the development of friendly analytical assays to monitor the drug localization and loading percentage in cochleates will be desired this nano drug carrier is currently under development by biodelivery sciences international having the first drugcochleate in the market place represents a big lisinopril-hctz 10-12.5 mg lup challenge for instance, when oral amphotericin � cochleates are ultimately available for patients, thus will provide a new opening in the treatment of systemic fungal infections references chien yw novel drug delivery systems drugs and the pharmaceutical sciences, vol marcel dekker new york, ny rathbone mj, hadgraft j and michael sr modifiedrelease drug delivery technology drugs and the pharmaceutical sciences, lisinopril-hctz 10-12.5 mg lup vol marcel dekker new york, ny charman wn lipids, lipophilic drugs and oral deliverysome emerging concepts j pharm sci bowtle w lipid formulations for oral drug delivery pharm technol eur attwood d microemulsions, in kreutrer j ed colloidal drug delivery systems marcel dekker new york, pp lawrence mj microemulsions as drug delivery vehicles curr opin colloid interface sci pouton cw lisinopril-hctz 10-12.5 mg lup and charman wn the potential of oily formulations for drug delivery to the gastrointestinal tract adv drug del rev muller rh, mader � and gohla s solid lipid nanoparticles lisinopril-hctz 10-12.5 mg lup sln for controlled drug delivery a review of the state of the art eur j pharm biopharm westesen � novel lipidbased colloidal dispersions as potential drug administration systems, expectations and lisinopril-hctz 10-12.5 mg lup reality colloid polym sci lamprecht a, bouligand y and benoit jp new lipid nanocapsules exhibit sustained release properties for amiodarone ] control rel lamprecht a, saumet jl, roux j and lisinopril-hctz 10-12.5 mg lup benoit jp lipid nanocarriers as drug delivery systems for ibuprofen in pain treatment intl} pharm razzaque ms, koji t, kumatori a and tagushi t cisplatininduced apoptosis in human proximal tubular lisinopril-hctz 10-12.5 mg lup epithelial cells is associated with the activation of the fasfas ligand system histochem cell biol razzaque ms, hossain ma, ahsan n and tagushi t lipid formulations of polyene antifungal drugs lisinopril-hctz 10-12.5 mg lup and attenuation of associated nephrotoxicity nephron hossain ma, maesaki s, kakeya h, noda t, yanagihara k, sasaki e, hirakata y, tomono k, tashiro t and kohno s efficacy of ns, lisinopril-hctz 10-12.5 mg lup a novel lipid nanosphere encapsulated amphotericin b, against cryptococcus neoformans antimicrob agents chemother otsubo t, maesaki s, yamamoto y, tomono k, tashiro t, seki j, tomii y, sonoke s and lisinopril-hctz 10-12.5 mg lup kohno s in vitro and in vivo activities of ns, a new lipid nanosphere incorporating amphotericin b, against aspergillus fumigatus antimicrob agents chemother trotta m, cavalli r, carlotti me, battaglia lisinopril-hctz 10-12.5 mg lup l and debernardi f solid lipid microparticles carrying insulin formed by solventinwater emulsiondiffusion technique int f pharm zarif l elongated supramolecular assemblies in drug delivery j control rel rev zarif lisinopril-hctz 10-12.5 mg lup l, graybill jr, perlin d and mannino rj cochleates new lipidbased drug delivery system ] liposome res papahadjopoulos d, vail wj, jacobson � and poste g cochleate lipid cylinders formation lisinopril-hctz 10-12.5 mg lup by fusion of unilamellar lipid vesicles bioehim biophys acta papahadjopoulos d large unilamellar vesicles luv and method of preparing the same us patent papahadjopoulos d, nir s and duzgunes n lisinopril-hctz 10-12.5 mg lup molecular mechanisms of calcium induced membrane fusion j bioenerg biomembr wilschut j and papahadjopoulos d ca induced fusion of phospholipid vesicles monitored by mixing of aqueous contents nature mannino rj lisinopril-hctz 10-12.5 mg lup and gouldfogerite s antigen cochleate formulations for oral and systemic vaccination, in levine mm ed new generation vaccines marcel dekker new york, pp zarif l and perlin d amphotericin � lisinopril-hctz 10-12.5 mg lup nanocochleates from formulation to oral efficacy drug del technol zarif l, graybill jr, perlin d, navjar l, bocanegra r and mannino rj antifungal activity of amphotericin � cochleates against candida lisinopril-hctz 10-12.5 mg lup albicans in a mouse model antimi crob agents chemother walsh tj, viviani ma, arathoon e, chiou c, ghannoum m, groll ah and odds fc new targets and delivery systems lisinopril-hctz 10-12.5 mg lup for antifungal therapy medmycol supp l biodelivery sertraline hcl prescription assistance program sciences wwwbiodeliverysciencescom unger e method for delivering bioactive agents using cochleates us b zarif l, jin t, segarra i and mannino rj new lisinopril-hctz 10-12.5 mg lup cochleate formulations, process of preparation and their use for the delivery of biologically relevant molecules pct application wool a zarif l and mannino rj cochleates lipidbased vehicles for gene delivery lisinopril-hctz 10-12.5 mg lup concept, achievements and future development, in habib n ed cancer gene therapy past achievements and future challenges kluwer academicplenum publishers new york, pp graham i, gagne j and silvius jr lisinopril-hctz 10-12.5 mg lup kinetics and thermodynamics of calcium induced lateral phase separations in phosphatidic acid containing bilayers biochemistry archibald dd and mann s selfassembled microstructures from ,ethanediol suspensions of pure and binary mixtures lisinopril-hctz 10-12.5 mg lup of neutral and acidic biological galactosylce ramides chem phys lipids l holland jw, hui c, cullis pr and madden td polyethylene glycollipid conjugates regulate the calciuminduced fusion of liposomes composed lisinopril-hctz 10-12.5 mg lup of phos phatidylethanolamine and phosphatidylserine biochemistry villardita c, grioli s, salmeri g, nicoletti f and pennisi g multicenter clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration, clin lisinopril-hctz 10-12.5 mg lup trials ] crook th, tinklenberg j, yesavage j, petrie w, nunzi mg and massari dc effects of phosphatidylserine in ageassociated memory impairment neurology engle rr, satzger w and gunther w lisinopril-hctz 10-12.5 mg lup doubleblind crossover study of phosphatidylserine vs placebo in patients with early dementia of the alzheimer type eur neuropsychopharmacol amaducci l phosphatidylserine in the treatment of alzheimers disease results of a multicenter study psychopharmacol bull cennachi t, bertoldin t, farina c, fiori mg and crepaldi g cognitive decline in the elderly a double blind, placebocontrolled multicenter study on efficacy of phosphatidylserine lisinopril-hctz 10-12.5 mg lup administration aging guidin j et al effect of soy lecithin phosphatidylserine ps complex on memory impairment and mood in the functioning elderly dept geriatrics, kaplan hospital, rehovot, israel maggioni m, lisinopril-hctz 10-12.5 mg lup picotti gb, bondiolotti gp et al effects of phosphatidylserine therapy in geriatric patients with depressive disorders acta psychiatr scand nerozzi d, aceti f, melia e, magnani a, marino r, genovesi lisinopril-hctz 10-12.5 mg lup g, amalfitano m, cozza g, murgiano s, de giorgis g, et al phosphatidylserine and memory disorders in the aged clin per monteleone p, beinat l, tanzillo c, maj m and lisinopril-hctz 10-12.5 mg lup kemali d effects of phosphatidylserine on the neuroendocrine response to physical stress in humans neuroen docrinology monteleone p et al blunting by chronic phosphatidylserine administration of the stressinduced activation of lisinopril-hctz 10-12.5 mg lup the hypothalamopituitaryadrenal axis in healthy men eur ] clin pharmacol funfgeld ew, baggen m, nedwidek p, richstein � and mistlberger g double blind study with phosphatidylserine ps in parkinsonian lisinopril-hctz 10-12.5 mg lup patients with senile dementia of alzheimers type sdat prog clin res zarif l and tan f cochleates made with purified soy phosphatidylserine us al duzgunes n, nir s, wischut j, lisinopril-hctz 10-12.5 mg lup bentz j, newton c, portis a and papahadjopoulos d calcium and magnesium induced fusion of mixed phosphatidylserine phosphatidylcholine vesicles effect of ionbinding j membr biol portis a, newton c, pangborn lisinopril-hctz 10-12.5 mg lup w and papahadjopoulos d studies on the mechanism of membrane fusion evidence for an intermembrane caphospholipid complex, synergism with mg, and inhibition by spectrin biochemistry santangelo r, paderu p, delmas lisinopril-hctz 10-12.5 mg lup g, chen zw mannino r, zarif l and perlin d efficacy of oral cochleates amphotericin b in a mouse model of systemic candidiasis antimicrob agents chemother zarif l, segarra i, jin t, scolpino a, hyra d, daublin p, krause s, perlin ds, lambros c, graybill jr and mannino rj lipidbased cochleate system for oral and systemic delivery of drugs aaps lisinopril-hctz 10-12.5 mg mylan dist omeprazole cap 20 mg lup eastern regional meeting and exposition segarra i, hyramovshin da, chen zw, santangelo r, perlin d, paderu p, mannino rj and zarif l amb cochleates, a new lipidbased formulation for amphotericin b from iv pharmacokinetics to oral efficacy millenial world congress of pharmaceutical sciences, san franscisco, ca, april, pp segarra i, jin t, hyra d, mannino rj and zarif l oral administration of amphotericin � with a new ambcochleate formulation tissue distribution after single and multiple oral dose icaac abs segarra i, movshin d, mannino rj and zarif l pharmacokinetics and tissue distribution of amphotericin � in mice after oral administration of amb cochleates, a new effective lipidbased formulation for the oral treatment of systemic fungal infections icaac abs segarra i, lisinopril-hctz 10-12.5 mg lup chen zw, movshin da, tan f, mannino rj and zarif l tissue distribution of oral amphotericin � lipidbased cochleate formulation comparison with ambisome th international symposium on controlled release of lisinopril-hctz 10-12.5 mg lup bioactive materials, paris france, pp zarif l, segarra i, jin t, hyra d and mannino rj amphotericin � cochleates as a novel oral delivery system for the treatment of fungal infections th international symposium on controlled release of bioactive materials boston, ma, june perlin d, santangelo r, mannino r and zarif l oral delivery of cochleates containing amphotericin � camb lisinopril-hctz 10-12.5 mg lup is highly effective in a candidiasis murine model, focus fungal infect zarif l, segarra i, jin t, hyra d, perlin d, graybill jr and mannino jr oral and systemic delivery lisinopril-hctz 10-12.5 mg lup of amphotericin � mediated by cochleates aaps annual meeting and exposition, november zarif l, jin t, scolpino a and mannino rj are cochleates the new lipidbased carrier for oral drug delivery?