x � ?a � o in fig the high curvature areas are believed to be rich in the hydrophilic solulan c molecules, while the low curvature areas are rich in the less hydrophilic hexadecyl diglycerol ether this separation of molecules is believed to be stabilized by favorable bonding interactions between like arteminisin and prednisone for dogs cancer molecules the gel to liquid phase transition occurs at �� and as these polyhedral vesicles are heated to this temperature, they adopt a spherical morphology, and on cooling, do not completely revert to the polyhedral morphology the spherical morphology presumably results from the increased mobility of molecules in the bilayer conversion to spheres arteminisin and prednisone for dogs cancer reduces the viscosity of the niosomes polyhedral vesicles are thermoresponsive [fig b] and become leakier when heated to a temperature just below their phase transition temperature �c the polyhedral morphology is retained at �c and polyhedral vesicles devoid of solulan c are not thermoresponsive the thermoresponsive behaviour arises from a diminished hydrogen bonding arteminisin and prednisone for dogs cancer between the pol�oxyethylene chain and the solvent on heating as measured by viscometric means this diminished hydration of the hydrophilic amphiphile � solulan c as the temperature rises, leads to defects in the membrane and an increase in membrane permeability hydration values for solulan c micelles are ,gg and gg at �� and arteminisin and prednisone for dogs cancer �c respectively recently, polyhedral vesicle morphologies have been identified when other surfactants are formulated in the absence of cholesterol and the presence of solulan c, including examples such as polyoxyethylenecetyl ether and polyoxyethylenestearyl ethers these polyoxyethylene polyhedral vesicles fuse to form multilamellar tubes of m in length, when extruded under pressure, thus arteminisin and prednisone for dogs cancer offering the possibility of making entirely new biomimetic materials vesicle preparation vesicle formation requires an input of energy either in the form of gentle agitation or probe sonication usually, the surfactantlipid mixtures are hydrated in the presence of the drug in aqueous solution and the unentrapped drug separated by either ultracentrifugation, low pressure arteminisin and prednisone for dogs cancer gel filtration chromatography or exhaustive dialysis, since vesicle size is an important determinant of drug biodistribution, vesicle size may be subsequently reduced by extruding via nucleopore filters, microfluidization or high pressure homogenization due to the nonabundance of reactive groups within synthetic surfactants, these molecules are stable on storage and vesicles prepared from surfactants have been observed to remain morphologically stable for up to seven years niosome delivery applications a variety of nonionic surfactant vesicles have been employed as drug, vaccine and imaging agent delivery systems table the most popular surfactants used are the sorbitan amphiphiles span , span , span and span which incidentally are approved excipients details arteminisin and prednisone for dogs cancer follow on how researchers have sought to exploit the ability of niosomes to control the distribution of drug within the body for drug delivery, vaccine delivery and diagnostic imaging drug targeting anti cancer drugs anti cancer drugs such as the model drug doxorubicin, when encapsulated in sorbitan monostearate polyoxyethylene coated coated with solulan arteminisin and prednisone for dogs cancer c niosomes, circulate for prolonged periods the area under the plasma level time curve is increased sixfold by the niosomes when compared with the drug in solution, tumor levels are increased by and tumoricidal activity is doubled these particles circulate for prolonged periods due to the polyoxyethylene coating, which prevents particle recognition arteminisin and prednisone for dogs cancer and the uptake by the liver and spleen however, while a polyoxyethylene coat may improve the delivery of drugs to tumors by achieving long blood circulation times, niosomes devoid of polyoxyethylene coatings are also able to improve the tumoricidal activity of drugs such as doxorubicin table examples of niosomal delivery applications therapeuticformulation andadvantage arteminisin and prednisone for dogs cancer of niosomal reference prophylacticroute offormulation diagnostic areaadministration intravenous sorbitan monostearate doxorubicin niosomes intravenous hexadecyl triglycerol ether doxorubicin niosomes antiinfectives glaucoma neurological disorders vaccination intravenous sorbitan monostearate methotrexate niosomes intravenous hexadecyl triglycerol ether niosomes topically applied timolol maleate sorbitan monostearate niosomes coated with chitosan intravenous administration of npalmitoyl glucosamine vasoactive intestinal peptide vip niosomes arteminisin and prednisone for dogs cancer cancer intramuscular palmitoyl glycerol herpes simplex virus type niosomes increase in tumor drug levels and twice as active against mouse mac a murine tumors as the drug in solution increase in tumor drug levels and twice as active against si murine tumors as the drug in solution a fold increase in plasma levels arteminisin and prednisone for dogs cancer when compared to the drug in solution and improvements in tumouricidal activity against murine si tumors liver peak levels of antimony are twice those of the drug in solution and niosomal formulations are times as active in reducing the parasite burden as the drug in solution a sustained lowering of intraocular pressure arteminisin and prednisone for dogs cancer with formulations being twice as active as a commercial gel formulation delivery of vip to the brain when encapsulated in niosomes but not when administered as the drug in solution higher levels of neutralising antibodies than the antigen in phosphate buffered saline and a higher survival rate after challenge with the virus of arteminisin and prednisone for dogs cancer animals still surviving after days compared to a of animals dosed with antigen in phosphate buffered saline surviving after days vesicles prepared from synthetic amphiphiles table continued therapeuticformulation and prophylacticroute of diagnostic area administration delivery ofintravenous diagnosticnpalmitoyl imaging agentsglucosamine gadolinium niosomes and npalmitoyl glucosamine gadolinium niosomes coated with polyoxyethylene higher tumor pc tumor arteminisin and prednisone for dogs cancer advantage of niosomal reference formulation cells to muscle ratio of contrast agent h after dosing with glucose or polyoxyethylene bearing niosomes when compared to sorbitan monostearate niosomes methotrexate and vincristine, principally by altering drug biodistribution following intravenous administration such that the drug is targeted to some extent to the tumor tissue the disparate arteminisin and prednisone for dogs cancer nature of the tumor vasculature is responsible for trapping particulate matter within tumors anti infectives the targeting of antileishmanial drugs to the liver, the site of pathology, is achievable with niosomal formulations hexadecyl triglycerol sodium stibogluconate niosomes are rapidly taken up by the liver producing peak levels of antimony that are twice that arteminisin and prednisone for dogs cancer achieved with the drug in solution the niosomes are thought to be taken up by macrophages in the liver the antiparasitic activity of sodium stibogluconate is increased fold by encapsulation into niosomes however, it must be noted that splenic and bone marrow parasites are more difficult to reach and eradicate delivery to arteminisin and prednisone for dogs cancer the bra in delivery of peptides to areas beyond the blood brain barrier is a major challenge, however, there is evidence that glucose coated niosomes may be able to achieve brain delivery of hydrophilic peptides these vesicles are believed to exploit the glucose transporter at the blood brain barrier, possibly by initially concentrating arteminisin and prednisone for dogs cancer drug at the barrier, and have been shown to deliver intact vasoactive intestinal peptide to the posterior and anterior parts of the brain topical use of niosomes transdermal the topical application of niosome encapsulated drugs results in the enhanced delivery of drugs through the stratum corneum, and delivery is specifically enhanced when hydrophilic arteminisin and prednisone for dogs cancer surfactants such as polyoxyethylenedodecyl ether or polyoxyethylenelauryl ester are used to produce flexible or elastic vesicles, which have similar flexible bilayer properties to the phospholipid transfersomes ocular niosomal formulations for the topical treatment of glaucoma have emerged in the form of carbopol p coated sorbitan monostearate acetazolamide niosomes, both chitosan and carbopol p coated sorbitan monostearate timolol maleate niosomes and sorbitan monopalmitate timolol maleate discomes discome formulations with a particle size of �� produce a sustained lowering of intraocular pressure when compared with normal niosomes the large particle size of the discomes is believed to limit ocular clearance polymer coatings are used to promote bioadhesion arteminisin and prednisone for dogs cancer and to prolong the drug residence time within the eye and the result is a prolonged lowering of intraocular pressure chitosan is a superior bioadhesive than carbopol in these ocular formulations the acetazolamide formulations showed comparable activity to a marketed formulation � dorzolamide dorzox and activity was sustained for up to hrs the arteminisin and prednisone for dogs cancer timolol maleate sorbitan monostearate niosome formulation on the other hand was twice as active as a marketed gel formulation all these topical niosome formulations are able to better localize drug activity to the eye, when compared with the drug in solution, thus minimizing deleterious systemic effects niosomal vaccines the niosomal encapsulation of both arteminisin and prednisone for dogs cancer antigens and dna encoding for antigens results in an enhancement of the humoral and cellular immune response to the said antigens although surfactants have immunostimulatory properties, the adjuvancy is attributed to the actual encapsulation of the antigen and its presentation as a particle enhanced protection against an infectious challenge has also been demonstrated arteminisin and prednisone for dogs cancer in mice that are vaccinated against herpes simplex virus type l niosomes as imaging agents targeting tumor glucose receptors is a viable method of imaging tumors, npalmitoyl glucosamine niosomes coated with polyoxyethylene and encapsulating gadolinium salts target pc tumor cells on tail vein injection delivery to tumors is sustained as targeting was still arteminisin and prednisone for dogs cancer observed hrs after dosing with the niosomes bearing both glucose and polyoxyethylene units on their surface tumor levels were higher with the use of glycosylated, polyoxyethylene coated niosomes when compared with plain sorbitan monostearate niosomes, and it is thus concluded that the presence of either glucose or polyoxyethylene on the niosome surface arteminisin and prednisone for dogs cancer enables tumor targeting of the contrast agent conclusions the past three decades have witnessed an explosion in the study of synthetic amphiphile vesicles, prepared either from polymers polymeric vesicles or from low molecular weight nonionic surfactants niosomes these nanosystems microsystems are able to encapsulate drugs and other bioactives and control the distribution of arteminisin and prednisone for dogs cancer the drug for pharmacological and ultimately clinical benefit a number of disease areas cancer, infectious diseases, glaucoma, etc are likely to benefit from the exploitation of these systems, as they are capable of delivering therapeutics, prophylactics and diagnostic agents in the case of the niosomes, a large number of the materials used to arteminisin and prednisone for dogs cancer fabricate the vesicles are already established excipients, and hence the development times of new medicines are likely to be shortened polymeric vesicles, by virtue of the tunable nature of the polymeric constituents, could give rise to more complex systems that are responsive to the pharmacological requirements of the pathology an exciting future awaits arteminisin and prednisone for dogs cancer these formulation materials references schillen k, bryskhe � and melnikova ys vesicles formed form polyoxyethylene polyoxypropylenepolyoxyethylene triblock copolymer in dilute aqueous solution macromolecules echegoyen le, hernandez jc, kaifer ae, gokel gw and echegoyen l aggregation of steroidal lariat ethers � the first example of nonionic liposomes niosomes from 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jc, uchegbu if and schatzlein a anticancer drug delivery with transferrin targeted polymeric chitosan vesicles pharm res eaton pe, jobe pg and kayson n polymerised vesicles am chem soc chen hm and langer r magneticallyresponsive polymerized liposomes as potential oral delivery vehicles pharm res cho i and chung �� cholesterolcontaining polymeric vesicles � syntheses, characterization and separation as a arteminisin and prednisone for dogs cancer solid powder macromolecules stauch o, uhlmann t, frohlich m, thomann r, elbadry m, kim yk and schubert r mimicking a cytoskeleton by coupling polynisopropylacrylamide to the inner leaflet of liposomal membranes effects of photopolymerization on vesicle shape and polymer architecture biomacromolecules cho i and �� yd synthesis and properties of tocopherolcontaining polymeric vesicle arteminisin and prednisone for dogs cancer systems macromol smp roks mfm, visser hgj, zwikker jw, verkley aj and nolte rjm polymerized vesicles derived from an 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uchegbu if, bouwstra j arteminisin and prednisone for dogs cancer a and florence at large diskshaped structures discomes in nonionic surfactant vesicle to micelle transitions ] phys chem photos pj, bacakova l, discher b, bates fs and discher de polymer vesicles in vivo correlations with peg molecular weight j control rel blume, g and cevc g molecular mechanism of the lipid vesicle longevity arteminisin and prednisone for dogs cancer in vivo biochim biophys acta brown md, gray al, tetley l, santovena a, rene j, schatzlein ag and uchegbu if in vitro and in vivo gene transfer with polyamino acid vesicles } control rel bagshawe kd, sharma sk, springer cj, antoniw p, boden ja, rogers gt, burke pj, melton rg and sherwood rf arteminisin and prednisone for dogs cancer antibody directed enzyme prodrug therapy adept clinical report dis mark napoli a, valentini m, tirelli n, muller m and hubbell ja oxidationresponsive polymeric vesicles nature mater uchegbu if and vyas sp nonionic surfactant based vesicles niosomes in drug delivery int} pharm rowe rc, sheskey pj and weller pj handbook of pharmaceutical excipients pharmaceutical arteminisin and prednisone for dogs cancer press london cable � an examination of the effects of surface modifications on the physicochemical and biological properties of nonionic surfactant vesicles, in pharmaceutical sciences university of strathclyde glasgow yoshioka t, sternberg � and florence at preparation and properties of vesicles niosomes of sorbitan monoesters span, span, span and span and a sor arteminisin and prednisone for dogs cancer bitan triester span int j pharm allen tm, hansen c, martin f, redemann � and yauyoung a liposomes containing synthetic lipid derivatives of polyethylene glycol show prolonged circulation halflives in vivo biochim biophys acta huang sk, kdl, hong k, friend ds and papahadjopoulos d microscopic localisation of sterically stabilised liposomes in colon arteminisin and prednisone for dogs cancer carcinoma bearing mice cancer res florence at, arunothayanun p, kiri s, bernard ms and uchegbu if some theological properties of nonionic surfactant vesicles and the determination of surface hydration j phys chem � nasseri � and florence at microtubules formed by capillary extrusion and fusion of surfactant vesicles int f pharm uchegbu if arteminisin and prednisone for dogs cancer synthetic surfactant vesicles harwood academic publishers amsterdam rogerson a, cummings j, willmott n and florence at the distribution of doxorubicin in mice following administration in niosomes j pharm pharmacol chandraprakash ks, udupa n, umadevi p and pillai gk effect of niosome encapsulation of methotrexate, macrophage activation on tissue distribution of methotrexate and tumour arteminisin and prednisone for dogs cancer size drug del parthasarathi g, udupa n, umadevi p and pillai gk niosome encapsulated of vincristine sulfate � improved anticancer activity with reduced toxicity in mice j drug targ hashizume h, baluk p, morikawa s, mclean jw, thurston g, roberge s, jain rk and mcdonald dm openings between defective endothelial cells explain tumor arteminisin and prednisone for dogs cancer vessel leakiness am } pathol baillie aj, coombs gh, dolan tf and laurie j nonionic surfactant vesicles, niosomes, as a delivery system for the antileishmanial drug sodium stibogluconate j pharm pharmacol collins m, carter ��, baillie aj and ogrady j the distribution of free and non ionic vesicular sodium stibogluconate in the arteminisin and prednisone for dogs cancer dog j drug targ williams dm, carter �� and baillie aj visceral leishmaniasis in the balbc mouse � a comparison of the in vivo activity of nonionic surfactant vesicle preparations of sodium stibogluconate } drug targ carter ��, baillie aj, alexander j and dolan tf the therapeutic effect of sodium stibogluconate in � arteminisin and prednisone for dogs cancer alb � mice infected with leishmania donovani is organ dependent } pharm pharmacol dufes c, gaillard f, uchegbu if, schatzlein ag, olivier jc, and muller jm glucose targeted niosomes deliver vasoactive intestinal peptide vip to the brain int j pharm reddy dn and udupa n formulation and evaluation of oral and transdermal preparations arteminisin and prednisone for dogs cancer of flurbiprofen and piroxicam incorporated with different carriers drug dev ind pharm schreier h and bouwstra j liposomes and niosomes as topical drug carriers � dermal and transdermal drugdelivery j control rel vanhal d, vanrensen a, devringer t, junginger h and bouwstra j diffusion of estradiol from nonionic surfactant vesicles through human stratum arteminisin and prednisone for dogs cancer corneum in vitro stp pharma sci fang jy, hong ct, chiu wt and wang yy effect of liposomes and niosomes on skin permeation of enoxacin int j pharm honeywellnguyen pl and bouwstra ja the in vitro transport of pergolide from surfactantbased elastic vesicles through human skin a suggested mechanism of action j control arteminisin and prednisone for dogs cancer rel cevc g, schatzlein a and blume g transdermal drug carriers � basic properties, optimization and transfer efficiency in the case of epicutaneously applied peptides control rel cevc g, blume g, schatzlein a, gebauer d and paul a the skin a pathway for systemic treatment with patches and lipidbased agent carriers adv arteminisin and prednisone for dogs cancer drug del rev aggarwal d, garg a and kaur ip development of a topical niosomal preparation of acetazolamide preparation and evaluation j pharm pharmacol aggarwal d and kaur ip improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system int} pharm vyas sp, mysore n, faitely v and venkatesan n arteminisin and prednisone for dogs cancer discoidal niosome based controlled ocular delivery of timolol maleate pharmazie brewer jm, roberts cw, conacher m, mccoll j, blarney ba, and alexander j an adjuvant formulation that preferentially induces t helper cell type cytokine and cd cytotoxic responses is associated with upregulation of il and suppression of il production vaccine res perrie y, arteminisin and prednisone for dogs cancer barralet je, mcneil s and vangala a surfactant vesiclemediated delivery of dna vaccines via the subcutaneous route intj pharm hilgers la, zigtermann gjwj and snippe h immunomodulating properties of amphiphilic agents, in autoimmunity and toxicology, me kammuller, n bioksma and w sienen eds elsevier, amsterdam, pp brewer jm and alexander j the adjuvant arteminisin and prednisone for dogs cancer activity of nonionic surfactant vesicles niosomes on the balbc humoral response to bovine serumalbumin immunology hassan y, brewer jm, alexander j and jennings r immune responses in mice induced by hsv glycoproteins presented with iscoms or nisv delivery systems vaccine luciani a, olivier j, clement og, siauve n, frija g and cuenod arteminisin and prednisone for dogs cancer � glucose receptor directed stealth niosomes for mr tumor detection preliminary studies in mice radiology luciani a, olivier jc, clement o, siauve n, brillet py, bessoud b, gazeau f, uchegbu if, kahn e, frija g and cuenod ca glucosereceptor mr imaging of tumors study in mice with pegylated paramagnetic niosomesradiology chandraprakash ks, udupa arteminisin and prednisone for dogs cancer n, umadevi p and pillai gk effect of macrophage activation on plasma disposition of niosomal hmethotrexate in sarcoma bearing mice drug targ this page is intentionally left blank recent advances in microemulsions as drug delivery vehicles m jayne lawrence and warankanga warisnoicharoen definition the term microemulsion originally introduced by schulman et al is arteminisin and prednisone for dogs cancer used to denote a thermodynamically stable, fluid, transparent or translucent dispersion of oil, and water, stabilized by an interfacial film of amphiphilic molecules ie molecules that possess within their structure a part that has an affinity for oil and a part that has affinity for water the amphiphilic molecules used to stabilize the arteminisin and prednisone for dogs cancer dispersion may be a pure surfactant, a polymeric surfactant, or a mixture of surfactants frequently in conjunction with a weakly amphiphilic molecule or cosur factant, typically a medium chain alcohol although at first glance, a seemingly simple definition, that causes much confusion in the literature, and in particular, the pharmaceutical literature, as to arteminisin and prednisone for dogs cancer what exactly constitutes a microemulsion such that every article on the subject always devotes some time to precisely defining what the authors mean by the term this present article is no different microemulsion versus an emulsion much of the confusion stems from the apparent relationship between a microemulsion and an emulsion in arteminisin and prednisone for dogs cancer fact, the two systems have little in common other than the fact that they are both dispersions of oil and water stabilized by an interfacial film of amphiphilic molecules the most significant difference between the two systems, is that a microemulsion forms spontaneously, and unlike an emulsion, it requires no mechanical work for arteminisin and prednisone for dogs cancer its formation a microemulsion is therefore thermodynami cally stable an emulsion, in contrast, generally requires considerable energy input for its preparation, and while it may possess some kinetic stability, it does not possess thermodynamic stability this is an important distinction between the two systems, and one which has important consequences for their preparation arteminisin and prednisone for dogs cancer and use for example, complex equipment and considerable cost in terms of energy input are required for the formation of an emulsion, whereas a microemulsion can be prepared using simple mixing equipment the requirement for energy input into a system for its formation provides a simple means of differentiating between a microemulsion and arteminisin and prednisone for dogs cancer an emulsion however, as it is virtually impossible to mix ingredients together without the input of some energy, the distinguishing feature is the energy level used, such that a microemulsion could be quite reasonably prepared using gentle heating or stirring to speed up its formation, whereas an emulsion would require the input arteminisin and prednisone for dogs cancer of considerably more energy, such as that supplied by high pressure homogenization or ultrasoni cation for its preparation it is worth noting, however, that a number of papers eg refs and incorrectly describe systems as being microemulsions, despite the fact that a considerable input of energy eg homogenization is required for the formation arteminisin and prednisone for dogs cancer of droplets, which in some instances are even outside the generally accepted size range for a microemulsion other differences between a microemulsion and an emulsion include the size of the regions of disperse phase in a microemulsion, the domains of disperse phase are typically less than nm and relatively uniform in size, whereas arteminisin and prednisone for dogs cancer an emulsion possess droplets of varying size in the general region of zm as a consequence of their small domain size, microemulsions are transparent or translucent while emulsions are usually cloudy it is worth noting however that it is possible to obtain an optically clear emulsion if the refractive index of the two arteminisin and prednisone for dogs cancer immiscible phases are of comparable values, in addition, although it is frequently stated that one of the immiscible phases is water, it is possible to prepare either a microemulsion or an emulsion using either a nonaqueous polar phase such as ethylene glycol, gylcerol or ethanol, or two immiscible oils such as a fluorocarbon arteminisin and prednisone for dogs cancer and a hydrocarbon or castor oil and silicone oil one important outcome of the small domain size and large interfacial area of a microemulsion is the large amount of surfactant required to stabilize the system, in the order of wt, as opposed to a to wt generally needed to stabilize an emulsion arteminisin and prednisone for dogs cancer microemulsion versus a nanoemulsion the confusion as to what differentiates a microemulsion and an emulsion has been further complicated by the emergence in the literature of another oil and water dispersion, known as a nanoemulsion, although the terms mini, or sub micron emulsion have also been used the distinction between a microemulsion and arteminisin and prednisone for dogs cancer a nanoemulsion is even more blurred because the description of a nanoemulsion is very similar to that of a microemulsion in that they are both oilinwater dispersions of small droplet diameter for nanoemulsions a range of nm is typically quoted and of narrow droplet size distribution, although the physical appearance of a nanoemulsion arteminisin and prednisone for dogs cancer resembles that of a microemulsion, in that both systems are transparent or translucent and of low viscosity, there is an essential difference between the two systems, namely that a nanoemulsion ie an emulsion is, at best, kinetically stable, while a microemulsion is therniodynamically stable as a consequence, many of the nanoemulsions reported in arteminisin and prednisone for dogs cancer the literature do not possess longterm stability some nanoemulsions have however exhibited sufficiently high levels of stability for them to be proposed as vehicles for drug delivery, it is worth commenting that, while the distinction between a nanoemulsion and an emulsion, in terms of their size, is rather arbitary, nanoemulsions because of arteminisin and prednisone for dogs cancer their small droplet size, possess a higher stability against sedimentation or creaming than an emulsion one supposed advantage of a nanoemulsion over a microemulsion is that it requires a lower surfactant concentration for its formation for example, nanoemulsion droplets of radius nm and containing wt isohexadecane, using only wt of a mixture of arteminisin and prednisone for dogs cancer polyoxyethylene dodecyl ether and polyoxyethylene dodecyl ether surfactants when comparing this surfactant concentration with the wt surfactant typically needed to prepare a microemulsion containing a comparable amount of oil, one should realize that the droplet size of a microemulsion thus produced would typically be nm consequently, in order to produce nanoemulsion droplets of arteminisin and prednisone for dogs cancer the comparable size, the amount of surfactant required would increase the surface area of the droplet varies with that of the square of the droplet radius to a comparable value the pertinent question in terms of drug delivery is what is most beneficial or the optimal size of the droplets recent results suggest arteminisin and prednisone for dogs cancer that small may not always be better, especially because of the need for large amounts of surfactant which, under certain circumstances, actually hinder drug absorption nanoemulsions, as a consequence of their relatively high kinetic stability, low viscosity, and transparencytranslucency, are very attractive for a range of industrial applications, including the pharmaceutical field where arteminisin and prednisone for dogs cancer they have been explored as drug delivery systems, it is worth noting however that the most stable nanoemulsions are generally, although not exclusively, prepared using expensive, high energy input methods such as microfluidization, ultrasonication, which makes their production expensive microemulsions figure shows a hypothetical ternary phase diagram with the possible extent of arteminisin and prednisone for dogs cancer the existence of a microemulsion marked temperature and pressure are constant if a surfactant or a mixture of surfactants, and a cosurfactant are used to prepare the microemulsion, then it is usual to keep the ratio of the two amphiphiles constant and to plot them as a single component, thereby allowing the production arteminisin and prednisone for dogs cancer of a pseudoternary phase diagram as can be seen in fig , it is possible to prepare microemulsion over a wide range of surfactant concentrations and oiltowater ratios, although in most systems, a microemulsion exists only over a restricted range of concentrations indeed, a microemulsion is only one of a number of possible oil, arteminisin and prednisone for dogs cancer water and surfactant association structures that can form, depending upon the chemical nature and concentration of each of the components, as well as the temperature and pressure other structures include gels and various mesomorphic phases regardless of whether a microemulsion is formed or not, generally, at very low surfactant concentrations, a large multiphase arteminisin and prednisone for dogs cancer region is seen, while at very high surfactant concentrations, liquid crystalline phases are frequently formed it is clear from fig that the microstructure of the microemulsion must vary over the range of possible microemulsion compositions at low oil or water volume lamcllar surfactant v ow microemulsion droplets � water wli microemulsion reverse micelles y ???
x � ?a � o in fig the high curvature areas are believed to be rich in the hydrophilic solulan c molecules, while the low curvature areas are rich in the less hydrophilic hexadecyl diglycerol ether this separation of molecules is believed to be stabilized by favorable bonding interactions between like arteminisin and prednisone for dogs cancer molecules the gel to liquid phase transition occurs at �� and as these polyhedral vesicles are heated to this temperature, they adopt a spherical morphology, and on cooling, do not completely revert to the polyhedral morphology the spherical morphology presumably results from the increased mobility of molecules in the bilayer conversion to spheres arteminisin and prednisone for dogs cancer reduces the viscosity of the niosomes polyhedral vesicles are thermoresponsive [fig b] and become leakier when heated to a temperature just below their phase transition temperature �c the polyhedral morphology is retained at �c and polyhedral vesicles devoid of solulan c are not thermoresponsive the thermoresponsive behaviour arises from a diminished hydrogen bonding arteminisin and prednisone for dogs cancer between the pol�oxyethylene chain and the solvent on heating as measured by viscometric means this diminished hydration of the hydrophilic amphiphile � solulan c as the temperature rises, leads to defects in the membrane and an increase in membrane permeability hydration values for solulan c micelles are ,gg and gg at �� and arteminisin and prednisone for dogs cancer �c respectively recently, polyhedral vesicle morphologies have been identified when other surfactants are formulated in the absence of cholesterol and the presence of solulan c, including examples such as polyoxyethylenecetyl ether and polyoxyethylenestearyl ethers these polyoxyethylene polyhedral vesicles fuse to form multilamellar tubes of m in length, when extruded under pressure, thus arteminisin and prednisone for dogs cancer offering the possibility of making entirely new biomimetic materials vesicle preparation vesicle formation requires an input of energy either in the form of gentle agitation or probe sonication usually, the surfactantlipid mixtures are hydrated in the presence of the drug in aqueous solution and the unentrapped drug separated by either ultracentrifugation, low pressure arteminisin and prednisone for dogs cancer gel filtration chromatography or exhaustive dialysis, since vesicle size is an important determinant of drug biodistribution, vesicle size may be subsequently reduced by extruding via nucleopore filters, microfluidization or high pressure homogenization due to the nonabundance of reactive groups within synthetic surfactants, these molecules are stable on storage and vesicles prepared from surfactants have been observed to remain morphologically stable for up to seven years niosome delivery applications a variety of nonionic surfactant vesicles have been employed as drug, vaccine and imaging agent delivery systems table the most popular surfactants used are the sorbitan amphiphiles span , span , span and span which incidentally are approved excipients details arteminisin and prednisone for dogs cancer follow on how researchers have sought to exploit the ability of niosomes to control the distribution of drug within the body for drug delivery, vaccine delivery and diagnostic imaging drug targeting anti cancer drugs anti cancer drugs such as the model drug doxorubicin, when encapsulated in sorbitan monostearate polyoxyethylene coated coated with solulan arteminisin and prednisone for dogs cancer c niosomes, circulate for prolonged periods the area under the plasma level time curve is increased sixfold by the niosomes when compared with the drug in solution, tumor levels are increased by and tumoricidal activity is doubled these particles circulate for prolonged periods due to the polyoxyethylene coating, which prevents particle recognition arteminisin and prednisone for dogs cancer and the uptake by the liver and spleen however, while a polyoxyethylene coat may improve the delivery of drugs to tumors by achieving long blood circulation times, niosomes devoid of polyoxyethylene coatings are also able to improve the tumoricidal activity of drugs such as doxorubicin table examples of niosomal delivery applications therapeuticformulation andadvantage arteminisin and prednisone for dogs cancer of niosomal reference prophylacticroute offormulation diagnostic areaadministration intravenous sorbitan monostearate doxorubicin niosomes intravenous hexadecyl triglycerol ether doxorubicin niosomes antiinfectives glaucoma neurological disorders vaccination intravenous sorbitan monostearate methotrexate niosomes intravenous hexadecyl triglycerol ether niosomes topically applied timolol maleate sorbitan monostearate niosomes coated with chitosan intravenous administration of npalmitoyl glucosamine vasoactive intestinal peptide vip niosomes arteminisin and prednisone for dogs cancer cancer intramuscular palmitoyl glycerol herpes simplex virus type niosomes increase in tumor drug levels and twice as active against mouse mac a murine tumors as the drug in solution increase in tumor drug levels and twice as active against si murine tumors as the drug in solution a fold increase in plasma levels arteminisin and prednisone for dogs cancer when compared to the drug in solution and improvements in tumouricidal activity against murine si tumors liver peak levels of antimony are twice those of the drug in solution and niosomal formulations are times as active in reducing the parasite burden as the drug in solution a sustained lowering of intraocular pressure arteminisin and prednisone for dogs cancer with formulations being twice as active as a commercial gel formulation delivery of vip to the brain when encapsulated in niosomes but not when administered as the drug in solution higher levels of neutralising antibodies than the antigen in phosphate buffered saline and a higher survival rate after challenge with the virus of arteminisin and prednisone for dogs cancer animals still surviving after days compared to a of animals dosed with antigen in phosphate buffered saline surviving after days vesicles prepared from synthetic amphiphiles table continued therapeuticformulation and prophylacticroute of diagnostic area administration delivery ofintravenous diagnosticnpalmitoyl imaging agentsglucosamine gadolinium niosomes and npalmitoyl glucosamine gadolinium niosomes coated with polyoxyethylene higher tumor pc tumor arteminisin and prednisone for dogs cancer advantage of niosomal reference formulation cells to muscle ratio of contrast agent h after dosing with glucose or polyoxyethylene bearing niosomes when compared to sorbitan monostearate niosomes methotrexate and vincristine, principally by altering drug biodistribution following intravenous administration such that the drug is targeted to some extent to the tumor tissue the disparate arteminisin and prednisone for dogs cancer nature of the tumor vasculature is responsible for trapping particulate matter within tumors anti infectives the targeting of antileishmanial drugs to the liver, the site of pathology, is achievable with niosomal formulations hexadecyl triglycerol sodium stibogluconate niosomes are rapidly taken up by the liver producing peak levels of antimony that are twice that arteminisin and prednisone for dogs cancer achieved with the drug in solution the niosomes are thought to be taken up by macrophages in the liver the antiparasitic activity of sodium stibogluconate is increased fold by encapsulation into niosomes however, it must be noted that splenic and bone marrow parasites are more difficult to reach and eradicate delivery to arteminisin and prednisone for dogs cancer the bra in delivery of peptides to areas beyond the blood brain barrier is a major challenge, however, there is evidence that glucose coated niosomes may be able to achieve brain delivery of hydrophilic peptides these vesicles are believed to exploit the glucose transporter at the blood brain barrier, possibly by initially concentrating arteminisin and prednisone for dogs cancer drug at the barrier, and have been shown to deliver intact vasoactive intestinal peptide to the posterior and anterior parts of the brain topical use of niosomes transdermal the topical application of niosome encapsulated drugs results in the enhanced delivery of drugs through the stratum corneum, and delivery is specifically enhanced when hydrophilic arteminisin and prednisone for dogs cancer surfactants such as polyoxyethylenedodecyl ether or polyoxyethylenelauryl ester are used to produce flexible or elastic vesicles, which have similar flexible bilayer properties to the phospholipid transfersomes ocular niosomal formulations for the topical treatment of glaucoma have emerged in the form of carbopol p coated sorbitan monostearate acetazolamide niosomes, both chitosan and carbopol p coated sorbitan monostearate timolol maleate niosomes and sorbitan monopalmitate timolol maleate discomes discome formulations with a particle size of �� produce a sustained lowering of intraocular pressure when compared with normal niosomes the large particle size of the discomes is believed to limit ocular clearance polymer coatings are used to promote bioadhesion arteminisin and prednisone for dogs cancer and to prolong the drug residence time within the eye and the result is a prolonged lowering of intraocular pressure chitosan is a superior bioadhesive than carbopol in these ocular formulations the acetazolamide formulations showed comparable activity to a marketed formulation � dorzolamide dorzox and activity was sustained for up to hrs the arteminisin and prednisone for dogs cancer timolol maleate sorbitan monostearate niosome formulation on the other hand was twice as active as a marketed gel formulation all these topical niosome formulations are able to better localize drug activity to the eye, when compared with the drug in solution, thus minimizing deleterious systemic effects niosomal vaccines the niosomal encapsulation of both arteminisin and prednisone for dogs cancer antigens and dna encoding for antigens results in an enhancement of the humoral and cellular immune response to the said antigens although surfactants have immunostimulatory properties, the adjuvancy is attributed to the actual encapsulation of the antigen and its presentation as a particle enhanced protection against an infectious challenge has also been demonstrated arteminisin and prednisone for dogs cancer in mice that are vaccinated against herpes simplex virus type l niosomes as imaging agents targeting tumor glucose receptors is a viable method of imaging tumors, npalmitoyl glucosamine niosomes coated with polyoxyethylene and encapsulating gadolinium salts target pc tumor cells on tail vein injection delivery to tumors is sustained as targeting was still arteminisin and prednisone for dogs cancer observed hrs after dosing with the niosomes bearing both glucose and polyoxyethylene units on their surface tumor levels were higher with the use of glycosylated, polyoxyethylene coated niosomes when compared with plain sorbitan monostearate niosomes, and it is thus concluded that the presence of either glucose or polyoxyethylene on the niosome surface arteminisin and prednisone for dogs cancer enables tumor targeting of the contrast agent conclusions the past three decades have witnessed an explosion in the study of synthetic amphiphile vesicles, prepared either from polymers polymeric vesicles or from low molecular weight nonionic surfactants niosomes these nanosystems microsystems are able to encapsulate drugs and other bioactives and control the distribution of arteminisin and prednisone for dogs cancer the drug for pharmacological and ultimately clinical benefit a number of disease areas cancer, infectious diseases, glaucoma, etc are likely to benefit from the 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baluk p, morikawa s, mclean jw, thurston g, roberge s, jain rk and mcdonald dm openings between defective endothelial cells explain tumor arteminisin and prednisone for dogs cancer vessel leakiness am } pathol baillie aj, coombs gh, dolan tf and laurie j nonionic surfactant vesicles, niosomes, as a delivery system for the antileishmanial drug sodium stibogluconate j pharm pharmacol collins m, carter ��, baillie aj and ogrady j the distribution of free and non ionic vesicular sodium stibogluconate in the arteminisin and prednisone for dogs cancer dog j drug targ williams dm, carter �� and baillie aj visceral leishmaniasis in the balbc mouse � a comparison of the in vivo activity of nonionic surfactant vesicle preparations of sodium stibogluconate } drug targ carter ��, baillie aj, alexander j and dolan tf the therapeutic effect of sodium stibogluconate in � arteminisin and prednisone for dogs cancer alb � mice infected with leishmania donovani is organ dependent } pharm pharmacol dufes c, gaillard f, uchegbu if, schatzlein ag, olivier jc, and muller jm glucose targeted niosomes deliver vasoactive intestinal peptide vip to the brain int j pharm reddy dn and udupa n formulation and evaluation of oral and transdermal preparations arteminisin and prednisone for dogs cancer of flurbiprofen and piroxicam incorporated with different carriers drug dev ind pharm schreier h and bouwstra j liposomes and niosomes as topical drug carriers � dermal and transdermal drugdelivery j control rel vanhal d, vanrensen a, devringer t, junginger h and bouwstra j diffusion of estradiol from nonionic surfactant vesicles through human stratum arteminisin and prednisone for dogs cancer corneum in vitro stp pharma sci fang jy, hong ct, chiu wt and wang yy effect of liposomes and niosomes on skin permeation of enoxacin int j pharm honeywellnguyen pl and bouwstra ja the in vitro transport of pergolide from surfactantbased elastic vesicles through human skin a suggested mechanism of action j control arteminisin and prednisone for dogs cancer rel cevc g, schatzlein a and blume g transdermal drug carriers � basic properties, optimization and transfer efficiency in the case of epicutaneously applied peptides control rel cevc g, blume g, schatzlein a, gebauer d and paul a the skin a pathway for systemic treatment with patches and lipidbased agent carriers adv arteminisin and prednisone for dogs cancer drug del rev aggarwal d, garg a and kaur ip development of a topical niosomal preparation of acetazolamide preparation and evaluation j pharm pharmacol aggarwal d and kaur ip improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system int} pharm vyas sp, mysore n, faitely v and venkatesan n arteminisin and prednisone for dogs cancer discoidal niosome based controlled ocular delivery of timolol maleate pharmazie brewer jm, roberts cw, conacher m, mccoll j, blarney ba, and alexander j an adjuvant formulation that preferentially induces t helper cell type cytokine and cd cytotoxic responses is associated with upregulation of il and suppression of il production vaccine res perrie y, arteminisin and prednisone for dogs cancer barralet je, mcneil s and vangala a surfactant vesiclemediated delivery of dna vaccines via the subcutaneous route intj pharm hilgers la, zigtermann gjwj and snippe h immunomodulating properties of amphiphilic agents, in autoimmunity and toxicology, me kammuller, n bioksma and w sienen eds elsevier, amsterdam, pp brewer jm and alexander j the adjuvant arteminisin and prednisone for dogs cancer activity of nonionic surfactant vesicles niosomes on the balbc humoral response to bovine serumalbumin immunology hassan y, brewer jm, alexander j and jennings r immune responses in mice induced by hsv glycoproteins presented with iscoms or nisv delivery systems vaccine luciani a, olivier j, clement og, siauve n, frija g and cuenod arteminisin and prednisone for dogs cancer � glucose receptor directed stealth niosomes for mr tumor detection preliminary studies in mice radiology luciani a, olivier jc, clement o, siauve n, brillet py, bessoud b, gazeau f, uchegbu if, kahn e, frija g and cuenod ca glucosereceptor mr imaging of tumors study in mice with pegylated paramagnetic niosomesradiology chandraprakash ks, udupa arteminisin and prednisone for dogs cancer n, umadevi p and pillai gk effect of macrophage activation on plasma disposition of niosomal hmethotrexate in sarcoma bearing mice drug targ this page is intentionally left blank recent advances in microemulsions as drug delivery vehicles m jayne lawrence and warankanga warisnoicharoen definition the term microemulsion originally introduced by schulman et al is arteminisin and prednisone for dogs cancer used to denote a thermodynamically stable, fluid, transparent or translucent dispersion of oil, and water, stabilized by an interfacial film of amphiphilic molecules ie molecules that possess within their structure a part that has an affinity for oil and a part that has affinity for water the amphiphilic molecules used to stabilize the arteminisin and prednisone for dogs cancer dispersion may be a pure surfactant, a polymeric surfactant, or a mixture of surfactants frequently in conjunction with a weakly amphiphilic molecule or cosur factant, typically a medium chain alcohol although at first glance, a seemingly simple definition, that causes much confusion in the literature, and in particular, the pharmaceutical literature, as to arteminisin and prednisone for dogs cancer what exactly constitutes a microemulsion such that every article on the subject always devotes some time to precisely defining what the authors mean by the term this present article is no different microemulsion versus an emulsion much of the confusion stems from the apparent relationship between a microemulsion and an emulsion in arteminisin and prednisone for dogs cancer fact, the two systems have little in common other than the fact that they are both dispersions of oil and water stabilized by an interfacial film of amphiphilic molecules the most significant difference between the two systems, is that a microemulsion forms spontaneously, and unlike an emulsion, it requires no mechanical work for arteminisin and prednisone for dogs cancer its formation a microemulsion is therefore thermodynami cally stable an emulsion, in contrast, generally requires considerable energy input for its preparation, and while it may possess some kinetic stability, it does not possess thermodynamic stability this is an important distinction between the two systems, and one which has important consequences for their preparation arteminisin and prednisone for dogs cancer and use for example, complex equipment and considerable cost in terms of energy input are required for the formation of an emulsion, whereas a microemulsion can be prepared using simple mixing equipment the requirement for energy input into a system for its formation provides a simple means of differentiating between a microemulsion and arteminisin and prednisone for dogs cancer an emulsion however, as it is virtually impossible to mix ingredients together without the input of some energy, the distinguishing feature is the energy level used, such that a microemulsion could be quite reasonably prepared using gentle heating or stirring to speed up its formation, whereas an emulsion would require the input arteminisin and prednisone for dogs cancer of considerably more energy, such as that supplied by high pressure homogenization or ultrasoni cation for its preparation it is worth noting, however, that a number of papers eg refs and incorrectly describe systems as being microemulsions, despite the fact that a considerable input of energy eg homogenization is required for the formation arteminisin and prednisone for dogs cancer of droplets, which in some instances are even outside the generally accepted size range for a microemulsion other differences between a microemulsion and an emulsion include the size of the regions of disperse phase in a microemulsion, the domains of disperse phase are typically less than nm and relatively uniform in size, whereas arteminisin and prednisone for dogs cancer an emulsion possess droplets of varying size in the general region of zm as a consequence of their small domain size, microemulsions are transparent or translucent while emulsions are usually cloudy it is worth noting however that it is possible to obtain an optically clear emulsion if the refractive index of the two arteminisin and prednisone for dogs cancer immiscible phases are of comparable values, in addition, although it is frequently stated that one of the immiscible phases is water, it is possible to prepare either a microemulsion or an emulsion using either a nonaqueous polar phase such as ethylene glycol, gylcerol or ethanol, or two immiscible oils such as a fluorocarbon arteminisin and prednisone for dogs cancer and a hydrocarbon or castor oil and silicone oil one important outcome of the small domain size and large interfacial area of a microemulsion is the large amount of surfactant required to stabilize the system, in the order of wt, as opposed to a to wt generally needed to stabilize an emulsion arteminisin and prednisone for dogs cancer microemulsion versus a nanoemulsion the confusion as to what differentiates a microemulsion and an emulsion has been further complicated by the emergence in the literature of another oil and water dispersion, known as a nanoemulsion, although the terms mini, or sub micron emulsion have also been used the distinction between a microemulsion and arteminisin and prednisone for dogs cancer a nanoemulsion is even more blurred because the description of a nanoemulsion is very similar to that of a microemulsion in that they are both oilinwater dispersions of small droplet diameter for nanoemulsions a range of nm is typically quoted and of narrow droplet size distribution, although the physical appearance of a nanoemulsion arteminisin and prednisone for dogs cancer resembles that of a microemulsion, in that both systems are transparent or translucent and of low viscosity, there is an essential difference between the two systems, namely that a nanoemulsion ie an emulsion is, at best, kinetically stable, while a microemulsion is therniodynamically stable as a consequence, many of the nanoemulsions reported in arteminisin and prednisone for dogs cancer the literature do not possess longterm stability some nanoemulsions have however exhibited sufficiently high levels of stability for them to be proposed as vehicles for drug delivery, it is worth commenting that, while the distinction between a nanoemulsion and an emulsion, in terms of their size, is rather arbitary, nanoemulsions because of arteminisin and prednisone for dogs cancer their small droplet size, possess a higher stability against sedimentation or creaming than an emulsion one supposed advantage of a nanoemulsion over a microemulsion is that it requires a lower surfactant concentration for its formation for example, nanoemulsion droplets of radius nm and containing wt isohexadecane, using only wt of a mixture of arteminisin and prednisone for dogs cancer polyoxyethylene dodecyl ether and polyoxyethylene dodecyl ether surfactants when comparing this surfactant concentration with the wt surfactant typically needed to prepare a microemulsion containing a comparable amount of oil, one should realize that the droplet size of a microemulsion thus produced would typically be nm consequently, in order to produce nanoemulsion droplets of arteminisin and prednisone for dogs cancer the comparable size, the amount of surfactant required would increase the surface area of the droplet varies with that of the square of the droplet radius to a comparable value the pertinent question in terms of drug delivery is what is most beneficial or the optimal size of the droplets recent results suggest arteminisin and prednisone for dogs cancer that small may not always be better, especially because of the need for large amounts of surfactant which, under certain circumstances, actually hinder drug absorption nanoemulsions, as a consequence of their relatively high kinetic stability, low viscosity, and transparencytranslucency, are very attractive for a range of industrial applications, including the pharmaceutical field where arteminisin and prednisone for dogs cancer they have been explored as drug delivery systems, it is worth noting however that the most stable nanoemulsions are generally, although not exclusively, prepared using expensive, high energy input methods such as microfluidization, ultrasonication, which makes their production expensive microemulsions figure shows a hypothetical ternary phase diagram with the possible extent of arteminisin and prednisone for dogs cancer the existence of a microemulsion marked temperature and pressure are constant if a surfactant or a mixture of surfactants, and a cosurfactant are used to prepare the microemulsion, then it is usual to keep the ratio of the two amphiphiles constant and to plot them as a single component, thereby allowing the production arteminisin and prednisone for dogs cancer of a pseudoternary phase diagram as can be seen in fig , it is possible to prepare microemulsion over a wide range of surfactant concentrations and oiltowater ratios, although in most systems, a microemulsion exists only over a restricted range of concentrations indeed, a microemulsion is only one of a number of possible oil, arteminisin and prednisone for dogs cancer water and surfactant association structures that can form, depending upon the chemical nature and concentration of each of the components, as well as the temperature and pressure other structures include gels and various mesomorphic phases regardless of whether a microemulsion is formed or not, generally, at very low surfactant concentrations, a large multiphase arteminisin and prednisone for dogs cancer region is seen, while at very high surfactant concentrations, liquid crystalline phases are frequently formed it is clear from fig that the microstructure of the microemulsion must vary over the range of possible microemulsion compositions at low oil or water volume lamcllar surfactant v ow microemulsion droplets � water wli microemulsion reverse micelles y ???