goh , and gcooh � ����� dendrimers at ph n = , rsd encapsulation efficiency of eda core ����� dendrimer ? g i �jii rdl jri i id at i� u e ?c o � v a v at l tris drug interaction prozac ultram sue nh peg pyr ae coona surface functionality fig encapsulation efficiency into famam dendrimers generations with amino nh, polyethyene glycol drug interaction prozac ultram peg, carbomethoxypyrrolidinone fyr, amidoethanol ae, sodium carboxylate coona, succinamic acid suc, and tris hydroxy me thy ammomethane tris surface groups core and amino surface g = , or ester surface g = at ph , and , the solubility enhancement of nifedipine was higher in the presence of esterterminated dendrimers than their aminoterminated analogues, possessing the same number of surface groups the drug interaction prozac ultram nifedipine solubility ex pec ted lv increased with the size of the dendrimers for ph , the sequence g g g g g g go was reported in another approach, the nonsteroidal antiinflammatory drug naproxen was covalently attached to unsymmetrical drug interaction prozac ultram polyarylester dendrimers to prepare a complex with enhanced water solubility of the drug and access for hydrplytic cleavage e t drug interaction prozac ultram ek k k k concentration mmolecular weight fig aqueous paclitaxel solubility as a function of the polyglycerol dendrimer concentration mean drug interaction prozac ultram � sd, n = g circle, g triangle, g square, and peg diamond left molecular weight dependency of dendrimers closed drug interaction prozac ultram circle and peg open circle on the aqueous paclitaxel solubility the concentration of dendrimers and peg was wt reproduced drug interaction prozac ultram with permission from ref copyright american chemical society of the bond between drug and carrier detailed results on the biological evaluation of these complexes have not been reported the anticancer drug paclitaxel, which is being used to treat metastatic breast drug interaction prozac ultram and ovarian cancers and kaposis sarcoma, has poor water solubility to enhance its bioavailability, paclitaxel has been encapsulated into drug interaction prozac ultram polyglycerol dendrimers, resulting in a ,fold improved water solubility compared with the pure drug, which is much higher than that drug interaction prozac ultram found for peg, a commonly used linear chain cosolvent or hydrotropic agent fig the drug release rate was a function of the dendrimer generation generation ����� dendrimers with hydroxy surface have been utilized to improve the bioavailability of the corticosteroid methylprednisolone, which decreases inflammation by stabilizing leukocyte lysosomal membrane by connecting the drug to the dendrimer using glutaric acid drug interaction prozac ultram as the spacer, a payload of wt was achieved the drugdendrimer complex was taken up by a human lung epithelial carcinoma cells and mostly localized in the cytosol the complex showed a pharmacological activity comparable to the free drug as drug interaction prozac ultram measured by the inhibition of the prostaglandin secretion doxorubicin and camptothecin � selfimmolative dendritic prodrugs an exciting new approach to drug interaction prozac ultram dendritic drug delivery involves the utilization of a drug as lamictal lesions a part of the dendritic molecule selfimmolative dendrimers have drug interaction prozac ultram recently been developed and introduced as a potential platform for a multiprodrug these unique structural dendrimers can release all of drug interaction prozac ultram their outer branch units through fig mechanism of dimeric prodrug activation by a single enzymatic cleavage reproduced with permission from ref copyright american chemical society a selfimmolative chain fragmentation, initiated by a single cleavage at the den drimers core drug interaction prozac ultram incorporation of drug molecules as these outer branch units and an enzyme substrate as the trigger can generate a multiprodrug drug interaction prozac ultram unit that will be activated with a single enzymatic cleavage fig the first generation of dendritic prodrugs with doxorubicin and camptothecin as branch units and retromichael focal trigger, which can be cleaved by the catalytic antibody c, has been reported drug interaction prozac ultram bioactivation of the dendritic prodrugs was evaluated in cellgrowth inhibition assay with the molt leukemia cell line in the drug interaction prozac ultram presence and absence of antibody c a remarkable increase in toxicity was observed dependent on the linker molecule, different numbers drug interaction prozac ultram of drug molecules can be released in one single activation step in a more classical approach to deliver doxorubicin, two drug interaction prozac ultram polyesterbased dendrimers generation with trisphenolic core were synthesized, one carrying a hydroxy surface, the other a triethylene glycol monomethyl ether drug interaction prozac ultram surface these dendrimers were compared with a arm polyethylene oxide star polymer, carrying g = dendritic polyester units at drug interaction prozac ultram the surface the star polymer gave the most promising results regarding cytotoxicity and systemic circulatory halflife hrs therefore, the anticancer drug interaction prozac ultram drug doxorubicin was covalently bound to this carrier via an acidlabile hydrazone linkage the cytotoxicity of doxorubicin was significantly reduced drug interaction prozac ultram and the drug was successfully taken up by several cancer cell lines photodynamic therapy pdt and boron neutron capture therapy drug interaction prozac ultram bnct dendrimers have been used to optimize the antitumor effect in photodynamic therapy pdt and boron neutron capture therapy drug interaction prozac ultram bnct one of the newest developments in the dendrimer field is their application to photodynamic therapy pdt this cancer treatment drug interaction prozac ultram involves the administration of a lightactivated photosensitizing moiety that selectively concentrates in diseased tissue subsequent activation of the photosensitizer leads drug interaction prozac ultram to the generation of reactive oxygen, primarily singlet oxygen, that damages intracellular components such as lipids and amino acid drug interaction prozac ultram residues through oxidation, ultimately leading to cell death by apoptosis disadvantages of currently used photosensitizers include skin phototoxicity, poor selectivity for tumor tissue, poor water solubility, and difficulties in the treatment of solid tumors because of the impermeability of the skin and tissues to the visible light required to excite the chromophores in one set of studies, dendrimers have been drug interaction prozac ultram constructed around a light harvesting core ie a porphyrin to reduce the toxicity under nonirradiative conditions dark toxicity and drug interaction prozac ultram to prevent aggregation, and consequently, selfquenching of the porphyrin cores, these dendrimers have been further encapsulated into micelles for example, drug interaction prozac ultram polyethylene glycolbpolyaspartic acid and pegbpolyllysine micelles have been studied in this regard these micelles are stable under physiological conditions ph drug interaction prozac ultram to however, they disintegrate in the acidic intracellular endosomal compartment ph alternatively, the photosensitizer aminolevulinic acid has been attached to drug interaction prozac ultram the surface of dendrimers and studied as an agent for pdt of tumorigenic keratinocytes photosensitive dyes have been incorporated into dendrimers and utilized in pdt devices for example, uptake, toxicity, and the mechanism of photosensitization of the dye pheophorbide drug interaction prozac ultram a pheo was compared with its complex with diaminobutane polypropylene imine dab dendrimers in human leukemia cells in vitroi the drug interaction prozac ultram second therapy, boron neutron capture therapy, is a cancer treatment based on a nuclear capture reaction when b is irradiated with low energy or thermal neutrons, highly energetic �particles and li ions are produced, that are toxic to tumor drug interaction prozac ultram cells to achieve the desired effects, it is necessary to deliver b to tumor cells at a concentration of at drug interaction prozac ultram least atoms per cell high levels of boron accumulation in tumor tissue can be achieved by using boronated antibodies that are targeted towards tumor antigens however, this approach can impair the solubility and targeting efficiency of the antibodies one drug interaction prozac ultram study, involving intratumoral injection of a conjugation between a generation ����� dendrimer carrying boron atoms and cetuximab, a monoclonal antibody specific for the egf receptor, showed that the conjugate was present fig schematic presentation of an eda core g = drug interaction prozac ultram ����� dendrimer , the boron carrier ������������ , and the targeting ligand folic acid reproduced with permission from ref copyright american chemical drug interaction prozac ultram society at an almost fold higher concentration in brain tumors than in normal brain tissue to reduce the liver uptake observed for boronated ����� dendrimer conjugates, peg chains were attached onto the dendrimer surface, in addition to the borane clusters, to provide steric shielding as compared with a dendrimer without peg chains, the amount of liver uptake was found drug interaction prozac ultram to be less for pegconjugated dendrimers with an average of chains of peg but higher for dendrimers with chains drug interaction prozac ultram of peg folic acid moieties were also conjugated to the ends of the peg chains to enhance the uptake of drug interaction prozac ultram the dendrimers by tumors overexpressing folate receptors although this strategy was successful in enhancing localization of the molecules to tumors drug interaction prozac ultram in mice bearing jkfbp tumors expressing the folate receptor, it also led to an increase in the uptake of the dendrimers by the liver and kidneys nanoscaffolds for targeting ligands the surface of dendrimers provides an excellent platform for drug interaction prozac ultram the attachment of cell specific ligands, solubility modifiers, stealth molecules, reducing the interaction with macromolecules from the body defense system, drug interaction prozac ultram and imaging tags the ability to attach any or all of these molecules in a welldefined and controllable manner onto a robust dendritic surface, clearly differentiates dendrimers from other carriers such as micelles, liposomes, emulsion droplets, and engineered particles folic drug interaction prozac ultram acid one example of cellspecific dendritic carriers is a dendrimer modified with folic acid the membraneassociated high affinity folate drug interaction prozac fda and toprol generics par ultram receptor hfr is a folate binding protein that is overexpressed on the surface of a variety of cancer cells, and therefore, folatemodified dendrimers would be expected to internalize into these cells preferentially over normal cells via receptormediated endocytosis folate dendrimer conjugates have been shown to be wellsuited for targeted, cancer specific drug delivery of cytotoxic substances in a very recent study, branched polylglutamic acid chains were centered around ����� dendrimers generations and and polyethylene imine pei cores to create drug interaction prozac ultram new biodegradable polymers with improved biodistribution and targeting ability these constructs were surfaceterminated with polyethylene glycol chains to enhance their drug interaction prozac ultram biocompatibility, and folic acid ligands to introduce cell specific targeting cell binding studies have been performed using the epidermal carcinoma drug interaction prozac ultram cell line, kb carbohydrates in addition to folates, carbohydrates constitute another important class of biological recognition molecules, displaying a wide variety of spatial structures due to their branching possibility and anomericity to achieve sufficiently high binding affinities between simple drug interaction prozac ultram mono and oligosaccharide ligands and cell membrane receptors, these ligands have to be presented to the receptors in a multivalent drug interaction prozac ultram or cluster fashion the highly functionalized surface of dendrimers provides an excellent platform for such presentations the design, synthesis, and drug interaction prozac ultram biomedical use of glycodendrimers, as well as their application in diagnostic and for vaccinations, have been thoroughly reviewed recently drug interaction prozac ultram for example, the thomsen friedenreich carbohydrate antigen tantigen, jgallagalnac, which has been well documented as an important antigen for the drug interaction prozac ultram detection and immunotherapy of carcinomas, especially relevant to breast cancer, has been attached to the surface of ����� and other drug interaction prozac ultram dendrimers an enhanced binding affinity was observed for all glycodendrimers these constructs could have potential in blocking the metastatic sites drug interaction prozac ultram of invasive tumor cells a series of dendritic cyclodextrin derivatives, bearing multivalent mannosyl ligands, has been prepared and their drug interaction prozac ultram binding efficiency towards the plant lectin concanavalin a con a and a mammalian mannosespecific cell surface receptor from macrophages has been studied the effects of glycodendritic architecture on binding efficiency, molecular inclusion, lectinbinding properties, and the consequence of complex formation using the anticancer drug docetaxel on biological recognition were investigated di to tetravalent dendritic galabiosides, carrying galalgal moieties on their surfaces, were studied as inhibitors of pathogens based on bacterial species such as e coli and streptococcus suis attachment drug interaction prozac ultram of dendritic galabiosides onto cell surfaces would be expected to inhibit the attachment of bacteria using the same sugar ligandreceptor drug interaction prozac ultram interactions the study revealed a clear enhancement of the binding affinity between glycodendrons and cell surfaces, with an increasing number drug interaction prozac ultram of sugar moieties in a similar approach, glycodendrons carrying two to four jdgalactose moieties on their surface, while the drug interaction prozac ultram dendron core was connected to a proteindegrading enzyme, were synthesized these glycodendriproteins are expected to attach to the surface of drug interaction prozac ultram bacteria, allowing the enzyme to degrade the bacterial adhesin, hence rendering the bacteria incapable of attaching to the cell surfaces drug interaction prozac ultram anionic ����� dendrimers c = were conjugated to dglucosamine and dglucoseamine fisulfate these watersoluble conjugates not only revealed immunomodulatory and antian giogenic properties, but synergistically prevented scar tissue formation after glaucoma filtration surgery in a validated and clinically relevant drug interaction prozac ultram rabbit study, the long term success rate was increased from to using these d end rimerconjugates antibodies and biotinavidin binding drug interaction prozac ultram generation ����� dendrimerendrimers with amino surface were conjugated to fluorescein isothio cyan ate as a means to analyze cell binding drug interaction prozac ultram and internalization two different antibodies, bca and j, which bind tocd and prostatespecific membrane antigen psma respectively, were used as mode!