pharm res gassmann p, list m, schweitzer a and sucker h hydrosols � alternatives for the parenteral applikation of poorly water soluble drugs eur f pharm biopharm list m and sucker h patno gb auweter hb, haberkorn c, horn h, lueddecke d and rauschenberger v, patent no dea tunick mhvh, diane l, cooke ph and malin el transmission electron microscopy of mozzarella cheeses made from microfluidized milk j agri food chem bruno rpm microfluidizer processor technology for high performance singulair aerator parts particle size reduction, mixing and dispersion microfluidizer processor technology sunstrom jem and marshikguerts � general route to nanocrystalline oxids by hydrodynamic cavitation chem mater gruverman ij and thum jr, production of nanostructures under turbulent collision reaction conditions � application to catalysts, superconductors, cmp abrasives, ceramics and other nanoparticles microfluidics research dearns r , atovaquone pharmaceutical compositions us patent us miiller rh, peters k, becker r and kruss � nanosuspensions � a novel formulation for the iv administration of poorly soluble drugs, singulair aerator parts in st world meeting metformin and barium of the international meeting on pharmaceutics, biopharmaceutics and pharmaceutical technology hosted by apgiapv budapest miiller rh, becker r, kruss � and peters � pharmaceutical nanosuspensions for medicament administration as systems with increased saturation solubility and rate of solution, in united states patent usa miiller rh, jacobs � and kayser � nanosuspensions for the formulation of poorly soluble drugs, in nielloud f and martimestres g eds pharmaceutical emulsions and suspensions, marcel dekker miiller rh, becker r, kruss singulair aerator parts � and peters � pharmazeutische nanosuspensio nen zur arzneistoffapplikation als systeme mit erhohter sattigungsloslichkeit und losungs geschwindigkeit german patent , us patent muller rh, dingier a, schneppe t and gohla s large scale production of solid lipid nanoparticles slntm and nanosuspensions dissocubes in wise d ed, handbook of pharmaceutical controlled release technology muller rh, jacobs � and kayser � dissocubes � a novel formulation for poorly soluble and poorly bioavailable drugs, in rathbone mj, hadgraft j, roberts ms eds, modified release singulair aerator parts drug delivery systems, marcel dekker rabinow be nanosuspensions in drug delivery nat rev muller rh nanopure technology for the production of drug nanocrystals and polymeric particles, in th world meeting adritelfapvapgi florence bushrab nf and muller rh nanocrystals of poorly soluble drugs for oral administration new drugs radtke m nanopure pure drug nanoparticles for the formulation of poorly soluble drugs new drugs fichera ma, keck cm and muller rh nanopure technology � drug nanocrystals for the delivery of poorly soluble drugs, in particles orlando fichera ma, wissing sa and muller rh effect of bar homogenisation pressure on particle diminution in drug suspensions, in apv niirnberg keck cm, bushrab nf and muller rh nanopure� nanocrystals for oral delivery of poorly soluble drugs, in particles orlando muller rh, mader � and krause � verfahren zur schonenden herstellung von hochfeinen micronanopartikeln, in pct application pctep germany kipp je, wong jct, doty mj and rebbeck cl microprecipitation method for preparing submicron suspensions, in united singulair aerator parts states patent baxter international inc deerfield, il usa moschwitzer j and muller rh method for the production of ultrafine submicron nanosuspensions pat application moschwitzer j phd thesis in preparation, in phd thesis pharmaceutical technology freie universitat berlin moschwitzer j and muller rh effective production of ibuprofen drug nanocrystals by high pressure homogenization using new twostep process, in aaps submitted nashville moschwitzer j and muller rh development of a new twostep process for the effective production drug nanocrystals by high pressure singulair aerator parts homogenization in aaps submitted nashville bushrab nf phd thesis in preparation, in phd thesis pharmaceutical technology freie universitat berlin moschwitzer j and muller rh from the drug nanocrystal to the final mucoadhesive oral dosage form, in international meeting on pharmaceutics, biopharmaceutics & pharmaceutical technology niirnberg moschwitzer j and muller rh nanosuspensions as formulation principle for chemical stabilization of chemically labile drugs, in international meeting on pharmaceutics, biopharmaceutics & pharmaceutical technology niirnberg wua yl, landisb a, hettricka e, novaka l, lynna singulair aerator parts l, chenc k, thompson a, higgins r, batrad u, shelukard s, kweia g and storeye g the role of biopharmaceutics in the development of a clinical nanoparticle formulation of mk a beagle dog model predicts improved bioavailability and diminished food effect on absorption in human int} pharm liversidge ggcp drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats int j pharm miiller rh preparation in form of a matrix materialauxiliary agent compound containing optionally singulair aerator parts an active substance europe keck cm et al production and optimisation of oral cyclosporine nanocrystals, in aaps baltimore krause � herstellung hochfeiner polymer und arzneistoffdispersionen und deren spruhtrocknung, in phd thesis pharmaceutical technology, freie universitat berlin khar a nanoedge technologies baxter company booklet yamaguchi h and hachioji i new antifungal agents currently under clinical development nippon kagaku ryoho gakkai zasshi slain dr, cleary pd and chapman sw intravenous itraconazole annals of pharmacotherapy smith a and hunneyball lm evaluation of polylactic acid as a biodegradable drug delivery system for parenteral administration int j pharm hernandeztrejo n, kayser o, mtiller rh and steckel h physical stability ofbupar vaquone nanosuspensions following nebulization with fetand ultrasonic nebulizers proceedings of the international meeting on pharmaceutics, biopharmaceutics and pharmaceutical technology, nuremberg germany hernandeztrejo n, kayser o, mtiller rh and steckel h characterization of nebulized buparvaquone nanosuspensions � effect of nebulization technology pharm res submitted patravale vbd, abhijit a and kulkarni rm nanosuspensions a promising drug delivery singulair aerator parts strategy j phar pharmacol pignatello r and puglisi g ocular tolerability of eudragit rs and rl nanosuspensions as carriers for ophthalmic controlled drug delivery pharm sci bucolo cm, puglisi g and pignatello r enhanced ocular antiinflammatory activity of ibuprofen carried by an eudragit rsi nanoparticle suspension ophthal res mtinster un, haberland c, jores a, mehnert w, rummel s, schaller k, korting m, zouboulis ch, blumepeytavi � and schaferkorting m ru myristate prodrug development for topical treatment of acne and androgenetic singulair aerator parts alopecia die phar mazie maia c, mehnert w and schaferkorting m solid lipid nanoparticles as drug carriers for topical glucocorticoids int j pharm mtiller rh dispersions for the formulation of slightly or poorly soluble drugs, in pctep pharmassol gmbh berlin mtiller rh et al solemuls � a novel technology for the formulation of iv emulsions with poorly soluble drugs int} pharm muller rh et al solemulsnovel technology for the formulation of iv emulsions with poorly soluble drugs int j pharm singulair aerator parts buttle i owemulsionen fur die intravenose applikation von arzneistoffen, in phd thesis pharmaceutical technology, freie universitat berlin akkar a and muller rh solubilisation by emulsification pharm ind akkar a and muller rh intravenous itraconazole emulsions produced by solemuls technology eur f pharm biopharm l akkar a et al solubilising poorly soluble antimycotic agents by emulsification via a solventfree process aaps pharmscitechpending, submitted akkar a and muller rh formulation of intravenous carbamazepine emulsions by solemuls technology eur j pharm biopharm akkar singulair aerator parts a poorly soluble drugs formulation by nanocrystals and solemuls technologies, in phd thesis pharmaceutical technology freie universitat berlin hann im and prentice hg lipidbased amphotericin b a review of the last years of use intj antimicrob agents lewis r antifungal therapy cost analysis patterson t f and mcginis m r, ed wwwdoctorfungusorg janoff a et al amphotericin b lipidcomplex ablc tm a molecular rationale for the attenuation of amphotericin � related toxicities j liposome res davis ss and washington � singulair aerator parts �� al cells and cell ghosts as drug carriers jos m lanao and m luisa sayalero introduction microparticle and nanoparticle polymeric systems currently occupy an important place in the field of drug delivery and targeting nevertheless, there are biological drug carriers that offer an efficient alternative to such systems within the different systems of biological carriers, of great importance are cells and cell ghosts, which are both efficient and highly compatible systems from the biological point of view, capable of singulair aerator parts providing the sustained release and specific delivery to tissues, organs and cells of drugs, enzymatic systems and genetic material cell systems such as bacterial ghosts, erythrocyte ghosts, polymorphonuclear leukocytes, apoptotic cells, tumor cells, dendritic cells, and more recently, genetically engineered stem cells, are all examples of how cell systems of very diverse nature can be suitably manipulated and loaded with drugs and other substances, to permit specific drug delivery in vivo with important therapeutic applications cell carriers for drug delivery singulair aerator parts are used in very different applications such as cancer therapy, cardiovascular disease, parkinsons, aids, gene therapy, etc table shows the classification of biological carriers for drug delivery based on the use of cells and cell ghosts bacterial ghosts bacterial ghosts are intact, nonliving, nondenatured bacterial cell envelopes devoid of cytoplasmic contents they are created by lysis of bacteria, but maintain table kinds of cells and cell ghosts used for drug and gene delivery cell carrier target encapsulated substance bacterial ghost singulair aerator parts tissues, macrophages, cells drugs, vaccines, genetic material erythrocyte ghost res, macrophages drugs, enzymes, peptides engineered stem cells tumor cells, t cells genetic material macrophages polymorphonuclear tissues drugs leucocytes apoptopic cells tumor cells drugs tumor cells tumor cells drugs denditric cells t cells drugs their cellular morphology and native surface antigenic structures, including their bioadhesive properties bacterial ghosts allow the encapsulation of drugs and other substances, and their specific attachment to mammalian tissues and cells this kind of cell carrier acts singulair aerator parts as a true drug delivery system, allowing the permanency of drugs in the systemic circulation to be increased together with tissuespecific targeting they are thus a promising alternative to conventional drug delivery systems such as liposomes or nanoparticles the main advantages of bacterial ghosts as delivery systems are the fact that they are nonliving, ie they can act as delivery systems of drugs, antigens or dna allow specific delivery to different tissues and cell types and are well captured by singulair aerator parts phagocytic cells and antigenpresenting cells as dendritic cells among the drawback of bacterial ghosts is the possibility that they might revert to being virulent, the possibility of horizontal gene transfer, the stability of the recombinant phenotype, and preexisting immunity against the carrier used usually, bacterial ghosts are produced by protein emediated lysis of gram negative bacteria the production of bacterial ghosts is based on the controlled expression of the bacteriophage phixderived lysis gene e expression of this gene from a plasmid in gramnegative bacteria leads to the formation of a transmembrane lysis tunnel structure that penetrates the inner and outer membranes, and is formed by protein e with border values fluctuating between nm in diameter protein e is a hydrophobic protein localized exclusively in the cell envelope emediated lysis has been achieved in many gramnegative bacteria scanning electron micrographs of elysed cells reveal that bacterial ghosts contain only one e hole in a bacterial ghost, although in a few cases, there are two holes the cytoplasm is expelled as a consequence of the high osmotic pressure inside the cell the collapse of membrane potential and the release of cytoplasmic components such as proteins, nucleic acids, etc occur simultaneously in the case of strains of e coli, this effect occurs within a period of min after the induction of expression the resulting empty bacterial cell envelope is considered a bacterial ghost bacterial ghosts show all the morphological, structural and immunogenic properties singulair aerator parts of a living cell since bacterial ghosts are derived from gramnegative bacteria that are able to adhere to structures such as fimbriae and lipopolysaccharide, they are used for specific binding to human tissue bacterial ghost drugloading is accomplished by the suspension of lyophilised bacterial ghosts in a buffered medium containing the drug the ghosts are then subjected to an incubation process varying from to min at �c they are then washed to remove excess drug in order to prevent rapid singulair aerator parts leakage of loaded watersoluble drugs or other substances, the bacterial ghosts are sealed by fusion of the cell membrane with membrane vesicles at the edges of the lysis pore for the sealing step, the bacterial ghosts suspension is incubated in the fusion buffer at �c for min figure shows a scheme of the production of bacterial ghosts by protein emediated bacterial lysis the in vitro release of drugs from loaded bacterial ghosts is performed from a suspension of drugloaded bacterial ghosts singulair aerator parts that is dialysed through a membrane suitable for excluding the ghosts dialysis is performed at �c in pbs buffer the concentrations of drug released into the buffer at preset times are quantified using an appropriate analytical technique in studies addressing the adherence and capture of loaded bacterial ghosts by target cells such as macrophages, human colorectal adenocarcinoma cells caco or dendritic cells, fluorescent markers such as fluorescein isothiocyanate fitc are used these allow adherence to be assessed using fluorescence microscopy singulair aerator parts and flow cytometry techniques, macrophages internalize bacterial ghosts to a greater extent than caco cells, studies carried out using confocal laser scanning microscopy with m haemolytica ghosts loaded with doxorubicin have shown that the drug was associated with the ghosts membranes and the inner lumen denditric cells that are professional phagocytic cells displaying the phagocytic capacity of antigens also have a good capacity for capturing bacterial ghosts, allowing the latter to be used as a vehicle for immunization and immunotherapy application of bacterial ghosts as a delivery system bacterial ghosts have important therapeutic applications they can be loaded with drugs, proteins and other substances, and can be targeted selectively to macrophages, tumors or endothelial cells i sealing drugloaded bacterial ghost fig production and drug loading of bacterial ghosts bacterial ghosts have been used as efficient drug delivery systems in the field of anticancer drugs bacterial ghosts obtained have been used as a delivery system of doxorubicin to human colorectal carcinoma singulair aerator parts cells cytotoxicity assays revealed that doxorubicinloaded ghosts show better antiproliferative capacity in caco cells than when free doxorubicin is used at the same concentration experiments have also been carried out using ecoli ghosts containing streptavidin, in order to increase the affinity of streptavidin for biotinylated compounds streptavidin loaded ghosts permit specific targeting to mucosal surfaces of the gastrointestinal and respiratory tracts, and also to phagocytic cells bacterial ghosts have been used as veterinary vaccines for the immunization of different animal singulair aerator parts species pasteurella multocida is a pathogen that causes morbidity and mortality in rabbits and its importance as a human pathogen has also been recognized p multocida ghosts have been used to immunize rabbits and mice similar results have been obtained in the immunization of cattle against pasteurellosis using pasteurella haemolytica ghosts actinobacillus pleuropneumoniae is a highly contagious microorganism and is the cause of porcine pleuropneumonia, infecting of pig populations however, actinobacillus pleuropneumoniae vaccines provide limited protection, since they decrease mortality singulair aerator parts but not morbidity in swine comparative studies have been carried out on immunization using a aerosol infection model for pigs vaccinated with loadedghosts or formalin inactivated actinobacillus pleuropneumoniae bacterins the results obtained showed that immunization with bacterial ghosts is more efficient in protecting pigs than bacteria bacterial ghosts can also be used as carriers of therapeutic dna or rna, the use of nucleic acid vaccines currently offers a technique for the development of prophylactic or therapeutic vaccines, based on the singulair aerator parts use of dna plasmids to induce immune responses by direct administration of dnaencoding antigenic proteins into animals, and this is also suitable for the induction of cytotoxic t cells, bacterial ghosts loaded with dna produce a high level of gene expression they can be used to enhance the mucosal immune response to target antigens expressed in the bacterial ghost system they can also be used for the specific targeting of dnaencoded antibodies to primary antigens located in cells ghosts of singulair aerator parts vibrium cholerae have been tested as antigen carriers of chlamidia trachomatis as potential vaccines for the control of genital infections produced by this bacteria recombinant vibrium cholerae ghosts, previously cloned with a major outer membrane protein of c trachomatis, afforded a high level of protective immunity against chlamydia in a murine model, mannheimia haemolytica is a pathogen that causes ovine mastitis m haemolytica ghosts loaded with plasmid dna stimulate the elicitation of efficient immune responses in mice, with no symptoms singulair aerator parts of acute or subacute toxicity during the experiment erythrocyte ghosts erythrocytes constitute the largest population of blood cells and are produced in the bone marrow they are mature blood cells that produce haemoglobin and carry out the exchange of oxygen and carbon dioxide between the lungs and the body tissues the term erythrocyte ghost attempts to define the resulting celllike structure when erythrocytes are subjected to a reversible process of osmotic lysis for more than years, many studies, both in singulair aerator parts vivo and in vitro, have been carried out to explore the use of erythrocyte ghosts as delivery systems of drugs and other substances erythrocyte ghosts are obtained from fresh erythrocytes coming from human blood or the blood of different animal species such as the rat, mouse, rabbit, etc, and are loaded with different types of substance, mainly drugs, peptides and enzymes, using different encapsulation methods the most frequent methods for collecting erythrocyte ghosts are osmosisbased methods such as hypotonic dialysis singulair aerator parts autologous erythrocyte ghosts offer a drug delivery system that can act as a reservoir of the drug or substance encapsulated, providing the sustained release of the drug into the organism together with selective targeting of the drugs to the reticuloendothelial system res of the liver, spleen and bone marrow the main advantages of carrier erythrocytes as drug delivery systems are their high degree of biocompatibility, the possibility of encapsulating the drug in a small amount of cells, the sustained release singulair aerator parts of the encapsulated drug or substance into the body, the selective targeting to the res, and the possibility of encapsulating substances of high molecular weight such as peptides among the drawbacks of these systems are the rapid leakage of some drugs out of the loaded erythrocytes and other problems related to their standardized preparation, storage and potential contamination erythrocyte ghosts can be obtained by diverse procedures such as hypotonic dilution, hypotonic preswelling, osmotic pulse, hypotonic hemolysis, hypotonic dialysis, electroporation, druginduced singulair aerator parts endocytosis and chemical methods, of the different ways of obtaining carrier erythrocytes, hypotonic dialysis is undoubtedly the most frequently used encapsulation method the reasons why it is so popular are its simplicity, its ease of application for a large number of drugs, enzymes and other substances, and because it is the method that best conserves the morphological and haematological properties of the erythrocyte ghosts obtained hypotonic dialysis is based on the exposure of red cells to the action of a singulair aerator parts hypotonic buffer, inducing cell swelling and the formation of pores that permit the drug to enter erythrocytes by means of a passive mechanism figure shows a scheme of the production of erythrocyte ghosts using a hypotonic dialysis method morphological inspection of erythrocyte ghosts is usually performed using transmission ��� or scanning sem electron microscopy some physical parameters of red cell membranes can also be studied from the diffusion of haemoglobin the haemolytic methods employed in the production of erythrocyte ghosts normally affect the haemolytic volume, surface area and tension figure shows the morphological changes observed by sem that occur in amikacinloaded erythrocytes due to hypotonic dialysis haematological parameters determine the effects of the procedure used to collect erythrocyte ghosts on their haematological properties among others, parameters such as reduced glutathione gsh, mean corpuscular volume mcv or red cell distribution width rdw, may be evaluated using a haematology analyzer dialysis bag erythrocytes drug ant isot min, �c, ph hypotonic buffer hypotonic singulair aerator parts dialysis min, c, ph fig production and drug loading of erythrocyte ghosts using a hypotonic dialysis method controlamikacin loaded erythrocyteserythrocytes fig sem micrographs of amikacin carrier erythrocytes obtained by hypotonic dialysis copyright from encapsulation and in vitro evaluation of amikacinloaded erythrocytes by c gutierrez millan reproduced by permission of taylor & francis group, llc, http wwwtaylorandfranciscom erythrocyte ghosts obtained by hypotonic dialysis show a decrease in the mean corpuscular volume and an increase in size dispersion erythrocyte ghosts show a singulair aerator parts greater degree of haemolysis than normal erythrocytes applications of erythrocyte ghosts as a delivery system erythrocyte ghosts can be used as potential drug delivery systems for enzymes, proteins and peptides, allowing sustained release into the systemic circulation and the delivery of these substances into the res resealing hypertonic buffer min, �c, ph drugloaded ghost erythrocytes in vitro release of drugs from loaded erythrocyte ghosts is usually tested using autologous plasma or an isoosmotic buffer at �c alternatively, a dialysis bag singulair aerator parts may be used the in vitro release of drugs and substances from loaded erythrocytes is usually a firstorder process, suggesting that the drug crosses the plasma membrane through a passive diffusion mechanism however, zeroorder release kinetics from loaded erythrocytes has also been described in vitro studies about the release kinetics of different drugs, enzymes and peptides from loaded erythrocytes have shown a slow release of the encapsulated substance when loaded erythrocyte ghosts are administered in vivo, changes in the pharmacokinetics singulair aerator parts of the encapsulated drugs occur, involving a systemic drug clearance related to the biological halflife of the erythrocytes increased serum halflives and the areas under the curve of drugs encapsulated in loaded erythrocyte ghosts, in comparison with the free drug, have been observed in animals and humans, at the same time, erythrocyte ghosts show a greater accumulation in tissues such as liver and spleen surface treatment of erythrocyte ghosts with substances such as glutaralde hyde, ascorbate, fe, diamide, band crosslinking singulair aerator parts reagents, trypsin, phenyl hydrazine and the nhydroxysuccinimide ester of biotin nhsbiotin, enhances the recognition of erythrocyte ghosts by macrophages in vitro and liver targeting in vivoi red cells may be used as carriers for some drugs such as antineoplastics, anti infective agents, antihypertensives, corticosteroids, etc thus, carrier erythrocytes have been widely studied as delivery systems of antineoplastic drugs for targeting the res located in organs such as liver and spleen different antineoplastic drugs have been encapsulated in erythrocyte ghosts in singulair aerator parts both in vitro and in vivo experiments increases have been obtained in average survival times in the treatment of mice bearing hepatomas, using methotrexate loaded carrier erythrocytes better recognition and capture of erythrocyte ghosts by macrophages have been obtained by using biotinylated erythrocytes containing methotrexate, by alterations to the membrane using band crosslinkers of erythrocyte ghosts containing etoposide, or by treatment of erythrocytes containing doxorubicin with glutaraldehyde antiinfective agents such as gentamicin, metronidazole, primaquine or imi zol have also been singulair aerator parts encapsulated in erythrocytes human erythrocytes containing gentamicin have proven to act as an efficient slowrelease system in vivo erythrocyte ghosts containing dexamethasone have been used in vivo in rabbits and humans a sustained release of dexamethasone in vivo in animals and humans was observed using carrier erythrocytes an increased antiinflammatory effect of the drug using carrier erythrocytes was observed in rabbits moreover, new prodrugs of antiopioid drugs such as naltrexone and naloxone have been encapsulated in erythrocytes to solve stability singulair aerator parts problems of the primary drug within the erythrocyte the encapsulated prodrugs are transformed into the active compound, following their release from erythrocyte ghosts in the fields of biochemistry and enzymatic therapeutics, the encapsulation of enzymes in erythrocytes has been studied in some depth enzymatic deficiencies or the treatment of specific illnesses may be approached using carrier erythrocytes loaded with enzymes the encapsulation of enzymes in erythrocytes solves some of the problems associated with enzyme therapy, such as the short halflife singulair aerator parts deriving from the action of plasma proteases, intolerant reactions, and the immunological disorders or allergic problems associated with the use of enzymes in therapeutics in vitro or in vivo studies with enzyme carrier erythrocytes have been performed using lasparaginase, hexokinase, alcohol dehydrogenase, aldehyde dehydrogenase, alcohol oxidase, glu tamate dehydrogenase, uricase, urokinase, lactate mono oxigenase, arginase, rhodanase, recombinant phosphotriestearase, deltaaminolevulinate dehydratase, urease, pegademase, brinase and alglucerase one of the best examples of the use in therapeutics of carrier erythrocytes containing enzymes, singulair aerator parts is that of lasparaginase encapsulated in human erythrocytes this has been successfully used in the treatment of acute lymphoblastic leukaemia in paediatrics erythrocyte ghosts may act as carrier systems for the delivery of peptides and proteins one of the main therapeutic applications of carrier erythrocytes in this field is that of antihiv peptides nucleoside analogues successfully inhibit the replication of immunodeficiency virases in view of the importance of the monocytemacrophage system in infection by hiv, it would be of maximum therapeutic singulair aerator parts interest to have available, the specific delivery of these therapeutic peptides into macrophages, which act as an important reservoir for the virus carrier erythrocytes containing antihiv peptides such as azidothimidine azt and didanosine ddi, significantly reduced the proviral dna content in comparison with the administration of free peptides in a murine aids model similar results have been obtained with ,dideoxycytidine triphosphateddctpdideoxycytidine ddcyd and azt prodrugs encapsulated in erythrocytes antineoplastic peptides such as fluoroaraamp fludarabine and fluorodeoxyuridine monophosphate fdump, a prodrug singulair aerator parts of fluro deoxyuridine fdurd, have been encapsulated in human carrier erythrocytes, behaving as a slowrelease delivery system macrophage uptake in vitro of antisense oligonucleotides may be increased by using carrier erythrocytes, other peptides, such as erythropoietin, heparin, dermaseptin s, interleukin or vaccines, have also been encapsulated in erythrocytes to increase their stability, acting as a slow release system with a prolonged halflife or for their specific targeting to bacterial membranes erythrocyte ghost derivatives can also be used as drug delivery singulair aerator parts systems nanoerythrosomes are erythrocyte membrane derivatives formed by spheroid vesicles, obtained by consecutive extrusion under nitrogen pressure through a polycarbonate filter membrane of a erythrocyte ghost suspension to produce small vesicles having an average diameter of nm in vitro and in vivo studies, carried out with nanoerythrosomes loaded with daunorubicin, have shown that when linked cova lently to nanoerythrosomes, the drug produces slow release of daunorubicin to the organism over a prolonged period of time and also that, in comparison singulair aerator parts with the free drug, cytotoxicity is greater the advantage of nanoerythrosomes, as compared with erythrocyte ghosts as drug delivery system, is that the former are able to escape from the reticuloendothelial system faster, in vitro studies have shown that the nanoerythrosomedaunorubicin complex is rapidly adsorbed and phagocytosed by macrophages liver, spleen and lungs are the organs in which nanoerythrosomes show the greatest capacity of accumulation another derivative of erythrocyte ghosts are reverse biomembrane vesicles loaded with drugs reverse biomembrane vesicles are produced by spontaneous vesiculation of the ghost erythrocyte membrane by endocytosis, using an appropriate vesiculating medium, producing small vesicles containing the drug within the parent ghost in vivo studies carried out using reverse biomembrane vesicles from erythrocyte ghosts loaded with doxorubicin in rats have revealed increases in the halflife and bioavailability of the drug, the liver and spleen, being the main organs for the clearance of this drug delivery system stem cells in gene therapy, a therapeutic transgene is singulair aerator parts introduced into the patient with a view of supplementing the functions of an abnormal gene to achieve the delivery of genetic material into the target cell, it is necessary to have a suitable carrier one important aim in the field of gene therapy is the design and development of gene carriers that encapsulate and protect the nucleic acid, and selectively release the vectornucleic acid complex to the target tissue, so that the genetic material will be released at the cellular singulair aerator parts level later in practice, there are several ways to achieve this the first is through the use of modified viruses containing the genetic material of interest the use of viruses for gene delivery has some drawbacks since it is limited to specific cells susceptible to being infected by the virus, and also the administration itself of the virus, has some immunological problems among others the second alternative is to use living cells modified genetically, such as stem cells, to deliver singulair aerator parts transgenic material into the body stem cell therapy is a new form of treatment, in which cells that have died or lost their function are replaced by healthy adult stem cells one advantage of this kind of cell is that it is possible to use samples from adult tissues or cells from the actual patient, for culture and subsequent implantation within the framework of stem cell research, the use of stem cells as delivery systems is a novel and attractive singulair aerator parts technique in the field of gene therapy, in which the cells of the patients themselves are genetically engineered, in order to introduce a therapeutic transgene used to deliver the genetic material a promising therapeutic strategy is the use of stem cells such as lymphocytes or fibroblasts as drug delivery systems experimental studies using stem cells as such systems have been tested in different therapeutic applications, especially in the field of cancer therapy considering the affinity of stem cells for tumor singulair aerator parts tissue, engineered stem cells have been successfully used for direct drug delivery to cancer cells in vitro cultures have been made of human mesenchymal stem cells from bone marrow that are transduced with an adenovirus vector carrying the human interferon betagene, which exerts therapeutic action against cancer engineered stem cells administered in vivo allow the delivery of the genetic material to cancer cells this new drug delivery system has proven to be efficient in the treatment of experimental neoplasms, such singulair aerator parts as lung cancer, in mice figure shows a scheme of the application of stem cells as carriers for gene delivery in experimental cancer therapy in vivo studies have also been carried out with neural stem cells engineered using adenoviral vectors to express interleukin, an oncolytic gene, whose efficiency has been demonstrated in the treatment of intracranial malignant gliomas in mice the used of haematopoietic stem cells has allowed antiviral genes to be introduced in both t cells and macrophages for singulair aerator parts the treatment of aids the use of stem cells as vehicles for gene therapy has also been suggested for the treatment of ischaemic heart disease ficoll engineered stem cells in vitro expansion fig application of stem cells as carriers for gene delivery in experimental cancer stem cells have also been employed in the field of antiepileptic therapy glial precursor cells, which release adenosine, have been derived from adenosine kinase embryonic stem cells in these experiments, the fibroblasts were engineered to singulair aerator parts release adenosine by inactivating adenosine metabolising enzymes after encapsulation within polyethersulfone hollowfibre capsules, and the introduction into mesenchymal stem cells interferon beta recombinant adenovirus the brain ventricles in a rat epilepsy model, the local release of adenosine allows drugresistant focal epilepsy to be treated these engineered cells were shown to suppress seizure activity polymorphonuclear leucocytes polymorphonuclear leucocytes pmn can be used as carriers of antibiotics in view of their selective targeting to sites of infection simply incubating pmn in the singulair aerator parts presence of high concentrations of antibiotic for hr at � � guarantees cell loading with the antibiotic pmn loaded with the macrolide azithromycin have been found to be efficient in an in vitro model that permits the delivery of the antibiotic in a bioactive form to chlamydia inclusions in polarized human endometrial epithelial hecb cells infected with chlamydia trachomatis pmn carriers allow the accumulation of large amounts of antibiotic in endometrial epithelial cells and its retention over long periods of singulair aerator parts time apoptopic cells programmed cellular death or apoptosis is a process that is controlled genetically in which the cells induce their own death in response to different types of stimulus such as the binding of deathinducing ligands to cell surface receptors a new strategy for drug delivery, called apoptopic induced drug delivery aidd, allows drug delivery to tumor cells upon the initiation of apoptosis by using a biological mechanism to achieve drug delivery this new system is based on the singulair aerator parts fact that apoptosis produces many changes in cell morphology that can be taken advantage of to achieve drug delivery apoptosis is reflected in enhanced membrane permeability, which favors the release of the encapsulated drug from the apoptotic cells to the tissue phagocytosis of drug loaded apoptotic carrier cells by tumor cells facilitates the localization of the drug within the tumor cell one advantage of the apoptotic induced drug delivery system aidd is that the drug carrier cells may be genetically singulair aerator parts engineered to modify their properties in vitro studies have been performed using s mouse lymphoma cells in which apoptosis is produced by exposure to dexamethasone the cytotoxicity of rg cells caused by temazolamideloadeds apoptotic cells was from to times higher than that of control temazolamideloaded s cells tumor cells a novel strategy for drug delivery based on the use of cell systems is the drug loaded tumor cell system dltc, developed for drug delivery and targeting in lung metastasis the singulair aerator parts tumor cells as drug carriers permit drug targeting to the bloodborne cancerous cells and the lungs as potential metastatic organs in practice, there is affinity between the plasma membrane of malignant tumor cells and the metastatic addressins expressed by the endothelial cells of the targeted organ in vivo studies have been carried out with dltc based on doxorubicinloaded bf murine melanoma cells doxorubicin accumulation in the mouse lung was several times higher than that seen after administering free doxorubicin dendritic singulair aerator parts cells dendritic cells dc are antigenpresenting cells they ingest antigen by phagocytosis, degrade it, and present fragments of the antigen at their surface dendritic cells have huge potential for immunization against a broad variety of diseases, because they travel throughout the body in search of pathogens indicative of infection or disease they are very important for the induction of t cell responses, which result in cellmediated immunity selective targeting of drugs incorporated in dendritic cells to t cells allows the singulair aerator parts response of these cells to be manipulated in vivo it has been shown that when incorporated into dendritic cells, the drug ogalactosylceramide improves their antitumor activity conclusions this chapter has focused on the use of cells and cell ghosts as delivery systems of drugs, enzymes or therapeutic genes the use of carrier cells such as bacterial ghosts, erythrocyte ghosts and engineered stem cells, for drug delivery and targeting are reviewed among others their high biocompatibility, together with their capacity for singulair aerator parts selective delivery and targeting in cells and specific tissues mean that these types of carrier are promising alternatives to the use of nano and microparticle systems, with applications in the fields of interest such as cancer therapy, cardiovascular therapy, aids, gene therapy, etc as an alternative to the use of cell carriers, modified viruses can also be used as drug delivery systems, especially in the field of gene therapy despite their potential interest, clinical studies with these types of carrier singulair aerator parts are still very limited, although in the near future, increase in the use and therapeutic applications of cell delivery systems is expected acknowledgments this chapter was supported in part by a project of the national research and development plan project saf references mainardes rm and silva lp drug delivery systems past, present, and future curr drug targets gutierrezmillan c, sayalero ml, castaneda az and lanao jm drug, enzyme and peptide delivery using erythrocytes as carriers j control rel huter v, singulair aerator parts szostak mp, gampfer j, prethaler s, wanner g, gabor f and lubitz w bacterial ghosts as drug carrier and targeting vehicles j control rel paul tr, knight st, raulston je and wyrick pb delivery of azithromycin to chlamydia trachomatisinfected polarized human endometrial epithelial cells by polymorphonuclear leucocytes j antimicrob chemother man j and gallo jm delivery of cytotoxic drugs from carrier cells to tumour cells by apoptosis apoptosis shao j, dehaven j, lamm d, weissman dn, runyan k, malanga cj, singulair aerator parts rojanasakul y and ma jk a cellbased drug delivery system for lung targeting ii therapeutic activities on bf melanoma in mouse lungs drug del fujii s, shimizu k, kronenberg m and steinman rm prolonged ifngamma producing nkt response induced with alphagalactosylceramideloaded dcs nat immunol yang sy, liu h and zhang jm gene therapy of rat malignant gliomas using neural stem cells expressing il cell biol jalava k, hensel a, szostak m, resch s and lubitz w bacterial ghosts as vaccine singulair aerator parts candidates for veterinary applications } control rel tabrizi ca, walcher p, mayr ub, stiedl t, binder m, mcgrath j and lubitz w bacterial ghostsbiological particles as delivery systems for antigens, nucleic acids and drugs curr opin biotechnol marchart j, dropmann g, lechleitner s, schlapp t, wanner g, szostak mp and lubitz w pasteurella multocida and pasteurella haemolyticaghosts new vaccine candidates vaccine altman e, young kd, garrett j, altman r and young r subcellular localization of lethal lysis proteins of bacteriophages � singulair aerator parts and �� j virol jalava k, eko fo, riedmann e and lubitz w bacterial ghosts as carrier and targeting systems for mucosal antigen delivery exp rev vaccines witte a and lubitz w dynamics of ��� protein emediated lysis of escherichia coli eur } biochem witte a, wanner g, blasi u, halfmann g, szostak m and lubitz w endogenous transmembrane tunnel formation mediated by phi xi lysis protein e bacteriol witte a, wanner g, sulzner m and lubitz w dynamics of singulair aerator parts phix protein e mediated lysis of escherichia coli protective immunity against pasteurellosis in cattle, induced by pasteurella haemolytica ghosts arch microbiol marchart j, rehagen m, dropmann g, szostak mp, alldinger s, lechleitner s, schlapp t, resch s and lubitz w protective immunity against pas teurellosis in cattle, induced by pasteurella haemolytica ghosts vaccine paukner s, kohl g, jalava � and lubitz w sealed bacterial ghostsnovel targeting vehicles for advanced drug delivery of watersoluble substances drug targ paukner s, kohl g singulair aerator parts and lubitz w bacterial ghosts as novel advanced drug delivery systems antiproliferative activity of loaded doxorubicin in human caco cells j control rel halsberger ag, khol g, felnerova d, mayr ub, furstladani s and lubitz w activation, stimulation and uptake of bacterial ghosts in antigen presenting cells j biotechnol huter v, hensel a, brand e and lubitz w improved protection against lung colonization by actinobacillus pleuropneumoniae ghosts characterization of a genetically inactivated vaccine} biotechnol hensel a, huter v, katinger a, singulair aerator parts raza p, strnistschie c, roesler u, brand e and lubitz w intramuscular immunization with genetically inactivated ghosts actinobacillus pleuropneumoniae serotype protects pigs against homologous aerosol challenge and prevents carrier state vaccine donnelly jj, ulmer jb, shiver jw and liu ma dna vaccines annu rev immunol felnerova d, kudela p, bizik j, haslberger a, hensel a, saalmuller a and lubitz w t cellspecific immune response induced by bacterial ghosts med sci monit br eko fo, lubitz w, mcmillan l, ramey k, singulair aerator parts moore tt, ananaba ga, lyn d, black cm and igietseme ju recombinant vibrio cholerae ghosts as a delivery vehicle for vaccinating against chlamydia trachomatis vaccine eko fo, he q, brown t, mcmillan l, ifere go, ananaba ga, lyn d, lubitz w, kellar kl, black cm and igietseme ju a novel recombinant multisubunit vaccine against chlamydia ] immunol ebensen t, paukner s, link c, kudela p, de domenico c, lubitz w and guzman ca bacterial ghosts are an efficient delivery system singulair aerator parts for dna vaccines ] immunol hoffman j magnani m and deloach jr eds the use of resealed erythrocytes as carriers and bioreactors advances in experimental medicine and biology , plenum press new york, pp gutierrez millan c, zarzuelo castaneda a, sayalero marinero ml and lanao jm factors associated with the performance of carrier erythrocytes obtained by hypotonic dialysis blood cells mol dis hamidi m and tajerzadeh h carrier erythrocytes an overview drug deliv gutierrezmillan c, arevalo m, zarzuelo a, gonzalez f, singulair aerator parts sayalero ml and lanao jm encapsulation and in vitro evaluation of amikacinloaded erythrocytes drug del pitt e, johnson cm and lewis da encapsulation of drugs in intact erythrocytes an intravenous delivery system biochem pharmacol ogiso t, iwaki m and ohtori a encapsulation of dexamethasone in rabbit erythrocytes, the disposition in circulation and antiinflammatory effect pharmacobio dyn hamidi m, tajerzadeh h, dehpour ar, rouini mr and ejtemaeemehr s in vitro characterization of human intact erythrocytes loaded by enalaprilat drug del bax singulair aerator parts be, bain md, talbot pj, parkerwilliams ej and chalmers ra survival of human carrier erythrocytes in vivo clin sci magnani m, rossi l, fraternale a, bianchi m, antonelli a, crinelli r and chiarantini l erythrocytemediated delivery of drugs, peptides and modified oligonucleotides gene ther tonetti m, astroff ab, satterfield w, de flora a, benatti u and deloach jr deloach, pharmacokinetic properties of doxorubicin encapsulated in glutaraldehyde treated canine erythrocytes am } vet res lizano c, perez mt and pinilla m singulair aerator parts mouse erythrocytes as carriers for coencapsu lated alcohol and aldehyde dehydrogenase obtained by electroporation in vivo survival rate in circulation, organ distribution and ethanol degradation life sci alvarez fj, herraez a, murciano jc, jordan ja, diez jc and tejedor mc in vivo survival and organ uptake of loaded carrier rat erythrocytes biochem muzykantov vr, zaltsman ab, smirnov md, samokhin gp and morgan bp targetsensitive immunoerythrocytes interaction of biotinylated red blood cells with immobilized avidin induces their lysis by complement bioehim biophys acta jordan ja, alvarez fj, lotero la, herraez a, diez jc and tejedor mc in vitro phagocytosis of carrier mouse red blood cells is increased by band crosslinking or diamide treatment biotechnol appl biochem lotero la, jordan ja, olmos g, alvarez fj, tejedor mc and diez jc differential in vitro and in vivo behaviour of mouse ascorbatefe and diamide oxidized erythrocytes biosci mishra pr and jain nk biotinylated methotrexate loaded erythrocytes for enhanced liver uptake a study on the singulair aerator parts rat j drug targ kruse ca, freehauf cl, patel kr and baldeschwieler jd mouse erythrocyte carriers osmotically loaded with methotrexate biotechnol appl biochem mishra pr and jain nk biotinylated methotrexate loaded erythrocytes for enhanced liver uptake a study on the rat int j pharm lotero la, olmos g and diez jc delivery to macrophages and toxic action of etoposide carried in mouse red blood cells bioehim biophys acta zocchi e, tonetti m, polvani c, guida l, benatti u and de singulair aerator parts flora a in vivo liver and lung targeting of adriamycin encapsulated in glutaraldehydetreated murine erythrocytes biotechnol appl biochem eichler hg, gasic s, bauer k, korn a and bacher s a in vivo clearance of antibodysensitized human drug carrier erythrocytes clin pharmacol ther eichler hg, rameis h, bauer k, korn a, bacher s and gasic s b survival of gentamicinloaded carrier erythrocytes in healthy human volunteers eur j clin investi ogiso t, iwaki m and ohtori a encapsulation of dexamethasone in singulair aerator parts rabbit erythrocytes, the disposition in circulation and antiinflammatory effect pharmacobio dyn rossi l, serafini s, cenerini l, picardi f, bigi l, panzani i and magnani m encapsulation of dexamethasone in rabbit erythrocytes, the disposition in circulation and antiinflammatory effect biotechnol appl biochem noelhocquet s, jabbouri s, lazar s, maunier jc, guillaumet g and ropars � magnani m and deloach jr eds, the use of resealed erythrocytes as carriers and bioreactorsadvances in experimental medicine and biology , plenum press, new york, pp singulair aerator parts kravtzoff r, desbois i, lamagnere jp, muh jp, valat c, chassaigne m, colomba p and ropars m improved pharmacodynamics of lasparaginaseloaded in human red blood cells eur j clin pharmacol rossi l, bianchi m and magnani m increased glucose metabolism by enzyme loaded erythrocytes in vitro and in vivo normalization of hyperglycemia in diabetic mice biotechnol appl biochem lizano c, sanz s, luque j and pinilla m in vitro study of alcohol dehydrogenase and acetaldehyde dehydrogenase encapsulated into human erythrocytes singulair aerator parts by an electroporation procedure biochim biophys acta magnani m, laguerre m, rossi l, bianchi m, ninfali p, mangani f and ropars � acetaldehyde dehydrogenaseloaded erythrocytes as bioreactors for the removal of blood acetaldehyde alcohol clin exp res magnani m, fazi a, magnani f, rossi l and mancini u methanol detoxification by enzymeloaded erythrocytes biotechnol biochem appl sanz s, lizano c, luque j and pinilla m in vitro and in vivo study of glutamate dehydrogenase encapsulated into mouse erythrocytes by hypotonic singulair aerator parts dialysis procedure life sci magnani m, mancini u, bianchi m and fazi a magnani m and deloach jr eds, the use of resealed erythrocytes as carriers and bioreactors advances in experimental medicine and biology , plenum press new york, pp ito y, ogiso t, iwaki m and atago h encapsulation of human urokinase in rabbit erythrocytes and its disposition in the circulation system in rabbits } pharmacobiodyn garin m, rossi l, luque j and magnani m lactate catabolism by enzymeloaded red singulair aerator parts blood cells biotechnol appl biochem adriaenssens k, karcher d, marescau b, van broeckhoven a and terheggen hc hyperargininemia the rat as a model for the human disease and the comparative response to enzyme replacement therapy with free arginase and arginase loaded erythrocytes in vivo int j biochem petrikovics i, pei l, mcguinn wd, cannon ep and way jl encapsulation of rhodanese and organic thiosulfonates by mouse erythrocytes fundam appl toxicol pei l, omburo g, mcguinn wd, petrikovics i, dave k, singulair aerator parts raushel fm, wild jr, deloach jr and way jl encapsulation of phosphotriesterase within murine erythrocytes toxicol appl pharmacol bustos nl and batlle am enzyme replacement therapy in porphyrias v in vivo correction of deltaaminolaevulinate dehydratase defective in erythrocytes in lead intoxicated animals by enzymeloaded red blood cell ghosts drug des del hamarat baysal s and uslan ah in vitro study of ureasealadh enzyme system encapsulated into human erythrocytes and research into its medical applications artif cells blood substit immobil biotechnol singulair aerator parts bax be, bain md, fairbanks ld, simmonds ha, webster ad and chalmers ra carrier erythrocyte entrapped adenosine deaminase therapy in adenosine deaminase deficiency adv exp med biol flynn g, hackett tj, mchale l and mchale ap encapsulation of the thrombolytic enzyme, brinase, in photosensitized erythrocytes a novel thrombolytic system based on photodynamic activation j photochem photobiol � biol bax be, bain md, ward cp, fensom ah and chalmers ra the entrapment of mannoseterminated glucocerebrosidase alglucerase in human carrier erythrocytes biochem singulair aerator parts soc trans s oettgen hf, old lj, boyse ea, campbell ha, philips fs, clarkson bd, tallal l, leeper rd, schwartz mk and �� jh inhibition of leukaemia in man by lasparaginase cancer res fraternale a, casabianca a, tonelli a, chiarantini l, brandi g and magnani m new drug combinations for the treatment of murine aids and macrophage protection eur j clin investig magnani m, rossi l, fraternale a, silvotti l, quintavalla f, piedimonte g, matteucci d, baldinotti f and bendinelli singulair aerator parts m fiv infection of macrophages in vitro and in vivo inhibition by dideoxycytidine triphosphate vet immunol immunopathol magnani m, bianchi m, rossi l and stocchi v human red blood cells as biore actors for the release of ,dideoxycytidine, an inhibitor of hiv infectivity biochem biophys res commun fraternale a, casabianca a, rossi l, chiarantini l, schiavano gf, palamara at, garaci e and magnani m erythrocytes as carriers of reduced glutathione gsh in the treatment of retroviral infections j antimicrob chemother singulair aerator parts fraternale a, rossi l and magnani m encapsulation, metabolism and release of fluoroaraamp from human erythrocytes biochim biophys acta alachi a, greenwood r and walker � buccal administration of erythrocyte ghostsinsulin in rats} control rel nielsen pe antisense peptide nucleic acids curr opin mol ther chiarantini l, cerasi a, fraternale a, andreoni f, scari s, giovine m, clavarino e and magnani m inhibition of macrophage inos by selective targeting of antisense pna biochemistry garin mi, lopez rm and luque j singulair aerator parts pharmacokinetic properties and in vivo biological activity of recombinant human erythropoietin encapsulated in red blood cells cytokine eichler hg, schneider w, raberger g, bacher s and pabinger i erythrocytes as carriers for heparin preliminary in vitro and animal studies res exp med feder r, nehushtai r and ��� a affinity driven molecular transfer from erythrocyte membrane to target cells peptides olmos g, lotero la, tejedor mc and diez jc delivery to macrophages of inter leukin loaded in mouse erythrocytes biosci singulair aerator parts rep polvani c, gasparini a, benatti u, de flora a, silvestri s, volpini g and nencioni l murine red blood cells as efficient carriers of three bacterial antigens for the production of specific and neutralizing antibodies biotechnol appl biochem garin mi, lopez rm, sanz s, pinilla m and luque j erythrocytes as carriers for recombinant human erythropoietin pharm res feder r, nehushtai r and ��� a affinity driven molecular transfer from erythrocyte membrane to target cells peptides lejeune a, moorjani singulair aerator parts m, gicquaud c, lacroix j, poyet p and gaudreault r nanoerythrosome, a new derivative of erythrocyte ghost preparation and antineoplastic potential as drug carrier for daunorubicin anticancer res moorjani m, lejeune a, gicquaud c, lacroix j, poyet p and gaudreault rc nanoerythrosomes, a new derivative of erythrocyte ghost ii identification of the mechanism of action anticancer res lejeune a, poyet p, gaudreault rc and gicquaud � nanoerythrosomes, a new derivative of erythrocyte ghost iii is phagocytosis involved in the mechanism of action?