Vesicle

The aim of this study was to evaluate the accuracy of ultrasonographic measurement of the deep portion of diencephalo-telencephalic vesicle (DPTV) in the prediction of delivery date in different size bitches. The effects of litter size and foetal sex ratio on the accuracy were also investigated. For this purpose, the growth curve of DPTV was derived in large size dogs (26-40 kg) and the results of the accuracy of the prediction were compared with those obtained in small (£10 kg) and medium (11-25 kg) size dogs by the application of the equations derived from the growth curve previously described. Ultrasonographic examinations were performed once a week during the second half of pregnancy in seven large size bitches (26-40 kg body weight). A linear regression model was adopted to analyse the relationship between the DPTV mean values and the days remaining to parturition. The results of regression analysis indicated that DPTV measurement in large size dogs is significantly and linearly related to the gestational age. Ultrasonographic measurements of DPTV were also performed during pregnancy in different size bitches with unknown breeding dates. Although the results indicated a similar accuracy of the prediction of the date of parturition in the different sizes of bitches, a higher accuracy was obtained in normal and large litter size compared with small litters. Foetal sex ratio did not affect the accuracy. In conclusion, this study demonstrated that the accuracy of the prediction of parturition day obtained by ultrasonographic evaluation of DPTV growth is reliable when specific formulae for different size dogs are applied. It should be noted that although foetal sex ratio does not affect the accuracy, the prediction could be less accurate when a small litter is present.

Transfersomes are highly efficient edge activator (EA)-based ultraflexible vesicles capable of, non-invasively, trespassing skin by virtue of their high, self-optimizing deformability. This investigation presents different approaches for the optimization of Transfersomes for enhanced transepidermal delivery of Diclofenac sodium (DS). Different methods of preparation, drug and lipid concentrations and vesicle compositions were employed, resulting in ultraflexible vesicles with diverse membrane characteristics. Evaluation of Transfersomes was implemented in terms of their shapes, sizes, entrapment efficiencies (EE%), relative deformabilities and in vitro skin permeation. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% (Span 85 > Span 80 > Na cholate > Na deoxycholate > Tween 80). Whereas, those prepared using 85:15% (w/w) ratio showed highest deformability (Tween 80 was superior to bile salts and spans). Transfersomes were proved significantly superior in terms of, the amount of drug deposited in the skin and the amount permeated, with an enhancement ratio of 2.45, when compared to a marketed product. The study proved that the type and concentration of EA, as well as, the method of preparation had great influences on the properties of Transfersomes. Hence, optimized Transfersomes can significantly increase transepidermal flux and prolong the release of DS, when applied non-occlusively.

D-and L-amphetamine sulphate isomers, methylphenidate and atomoxetine, are effective treatments for attention-deficit hyperactivity disorder (ADHD). This study provides a detailed comparison of their effects on the synaptosomal and vesicular accumulation of dopamine (DA) and noradrenaline (NA) and release in vitro in rat prefrontal cortex and striatum. D-Amphetamine was more potent than L-amphetamine at inhibiting accumulation of DA or NA in synaptosomes and vesicles. All drugs were weaker at inhibiting the accumulation of vesicular DA and NA compared to synaptosomal accumulation and more potently inhibited NA accumulation than DA. Methylphenidate was weak at inhibiting vesicular accumulation of DA and NA compared to its potent synaptosomal effects. The D-isomer had greater potency than the L-isomer on basal and electrically stimulated striatal DA release; however the L-isomer was 2-fold more potent than the D-isomer on basal fronto-cortical NA release. The selective DA reuptake inhibitor, GBR-12909 and NA reuptake inhibitors, maprotiline and atomoxetine, had different release profiles both on the potency and magnitude of basal and stimulated DA and NA release compared to the amphetamine isomers. These results identify distinct pharmacological action by the amphetamine isomers on dopaminergic and noradrenergic neurotransmission, which may impact on their therapeutic effects in the treatment of ADHD.

For decades scientists have been working on closed systems for transportation, catalysis and protection, which are inspired by natural cells. Only recently polymer based systems have emerged for these systems, since they are more robust, give protection from the environment and give a more stable membrane. Various methods have been developed to prepare polymer based capsules. They can be made by self-assembly, templating, in situ polymerization or precipitation. Their application has been explored in various areas e.g. drug delivery, diagnostics, sensors and nano reactors. Considering the output in this field has substantially grown, more developments can be expected from this latter application.

The dialysis of micellar and vesicular systems, through a cellulose acetate membrane permeable only to monomer surfactant, has been investigated for the system sodium decanoate/decanoic acid as a function of pH, in pH regions where micelles (pH 9) or vesicles (pH 7.5) are present. The results provide data that are helpful in establishing the thermodynamic state of the systems and the interplay of the relevant equilibrium and kinetic considerations. Additionally, the kinetics of spontaneous formation and destruction of vesicles when subjected to a pH-jump perturbation have been studied. Changes are rapid, taking place over a time scale of a few seconds.

Gram-negative bacteria have the ability to produce outer membrane-derived vesicles (OMVs) that are released into the extracellular milieu. Even though this intriguing phenomenon is well-known since many years, various aspects of bacterial OMVs are not fully described and are still in the process of being characterized in detail. One major reason for this is that depending on the bacterial species and its respective ecological niche, OMVs exhibit an enormous functional diversity. Research of the past years has clearly shown that OMVs of many pathogenic bacteria contribute to the virulence potential by enriching virulence factors and delivering them over long distances, superseding direct bacterial contact with their host. The subsequent interaction of OMVs with the host can occur at different levels regarding the type of immune response or the target cell type and may lead to different outcomes ranging from non-immunogenic activation or a pro-inflammatory response to cytotoxicity. In contrast to being virulence factors, OMVs are used for vaccination purposes in the combat against bacterial pathogens, and recent research thus is focused on to indirectly aim these versatile bacterial weapons against themselves.

The ability of a recently developed novel class of liposomes to promote dermal delivery of tretinoin (TRA) was evaluated. New penetration enhancer-containing vesicles (PEVs) were prepared adding to conventional phosphatidylcholine vesicles (control liposomes) different hydrophilic penetration enhancers: Oramix ® NS10 (OrNS10), Labrasol ® (Lab), Transcutol ® P (Trc), and propylene glycol (PG). Vesicles were characterized by morphology, size distribution, zeta potential, incorporation efficiency, stability, rheological behaviour, and deformability. Small, negatively charged, non-deformable, multilamellar vesicles were obtained. Rheological studies showed that PEVs had fluidity higher than conventional liposomes.

The trend towards personalized medicine and the long-standing wish to reduce drug consumption and unwanted side effects have been the driving force behind research on drug delivery vehicles that control localization, timing and dose of released cargo. Controlling location and timing of the release allows using more potent drugs as the interaction with the right target is ensured and enables sequential drug release. A particularly desired solution allows for externally triggered release of encapsulated compounds. Externally controlled release can be accomplished if drug delivery vehicles, such as liposomes or polyelectrolyte multilayer capsules, incorporate nanoparticle (NP) actuators. However, close control over the structure of the composite material is necessary to harness this potential. This review describes the assembly and characterization of NP functionalized liposomes and polyelectrolyte multilayer capsules that allow for externally triggered cargo release. Special attention is paid to the relationship between NP stability and the assembly and performance of NP functionalized drug delivery vehicles.

Supramolecular nanostructures assembled by polymeric amphiphiles have been intensively studied during the last two decades. Such nanocarriers may be engineered to possess on-demand bioresponsitivity for the prevention, diagnosis, and treatment of human diseases. The successful development of several nanoassembly-based polymer therapeutics further encouraged scientists to develop nano-vehicles to achieve controlled release, enhanced efficacy, improved specificity and reduced toxicity. Different from the abundant existing literatures on the hydrophobically or electrostatically driven self-assemblies and their therapeutic applications, this article reviews hostguest interaction mediated nanoassemblies, especially those constructed using cyclodextrins as the host entities. The excellent biocompatibility, complexation capacity, and chemical-sensitivity of cyclodextrin make cyclodextrin-containing polymers attractive to construct host-guest nanoassemblies. Such nanocarriers may be advantageous also because of the broad availability of cyclodextrins, their flexibility for structure/property modulation and their chemical-responsive characteristics.

Cryo-transmission electron microscopy (cryo-TEM) was employed to investigate the aggregate structure in dilute aqueous dispersions of egg-phosphatidylcholine (EPC), oleic acid (OA), and the lysophospholipid monooleoylphosphatidylcholine (MOPC). At physiological pH and salt concentration, a relatively monodisperse population of unilamellar liposomes was detected in mixtures containing equimolar concentrations of the three components. Threadlike micelles constituted the dominant aggregate structure in samples containing high concentrations of MOPC. Excess fatty acid forced, on the other hand, the system toward structures with net negative curvature. In the absence of phospholipid, cryo-TEM revealed bilayer fragments in coexistence with threadlike micelles in mixtures containing the same molar amount of MOPC and OA. External addition of MOPC to preformed EPC liposomes gave rise to a concentration dependent evolution of intermediate structures, including open liposomes and bilayer fragments. The structural rearrangements were found to be slow and permitted visualization of a number of interesting transition structures. In addition to the structural studies, static and time-resolved fluorescence measurements were employed to determine some fundamental parameters for MOPC micelles. The results indicate a critical micelle concentration of close to 5 µM and an aggregation number of approximately 142.

Transverse tubule vesicles were isolated from frog skeletal muscle by a procedure initially described by Rosemblatt et al. (J. Biol. Chem. 256, 8140-8148 (1981)) and later modified by Hidalgo et al. (J. Biol. Chem. 258, 13937-13945 (1983)). A large fraction of the isolated vesicles (80-90%) were sealed, as indicated by the detergent induced increase in (Na++ K+)-ATPase activity and ATP-dependent ouabain binding. To determine the orientation of the sealed vesicles binding of digoxin, a lipid soluble derivative of ouabain, was measured. The same values of ATP-dependent digoxin binding were found with or without detergents, indicating that all the vesicles that are sealed have the ATP site accessible, and hence are sealed with the cytoplasmic side-out (inside-out orientation). The transverse tubule preparation isolated from frog muscle is highly purified, as indicated by its cholesterol content and its (Na++ K+)-ATPase activity; negligible contamination with sarcoplasmic reticulum was observed, as indicated by the protein composition and the lack of measurable Ca 2 +-ATPase activity of the isolated transverse tubules. High initial rates of Mg 2 +-ATPase activity were found, with the peculiar property of being inhibited during the course of the reaction. Addition of lysophosphatidylcholine or saponin partially prevented the inhibition of Mg2+-ATPase activity during the reaction.

Despite the recent upsurge of theoretical reduced models for vesicle shape dynamics, comparisons with experiments have not been accomplished. We review the implications of some of the recently proposed models for vesicle dynamics, especially the Tumbling-Trembling domain regions of the phase plane and show that they all fail to capture the essential behavior of real vesicles for excess areas, \Delta, greater than 0.4. We emphasize new observations of shape harmonics and the role of thermal fluctuations.

The rates of oximolysis of p-nitrophenyl diphenyl phosphate (PNPDPP) by Acetophenoxime; 10-phenyl-10-hydroxyiminodecanoic acid; 4-(9-carboxynonanyl)-1-(9-carboxy-1-hydroyiminononanyl) benzene; 1-dodecyl-2-[(hydroxyimino)methyl]-pyridinium chloride (IV) and N-methylpyridinium-2-aldoxime chloride were determined in micelles of N-hexadecyl-N,N,N-trimethylammonium chloride (CTAC), N-hexadecyl-N,N-dimethylammonium propanesulfonate and dioctadecyldimethylammonium chloride (DODAC) vesicles. The effects of CTAC micelles and DODAC vesicles on the rates of oxymolysis of O,O-Diethyl O-(4-nitrophenyl) phosphate (paraoxon) by oxime IV were also determined. Analysis of micellar and vesicular effects on oximolysis of PNPDPP, using pseudophase or pseudophase with explicit consideration of ion exchange models, required the determination of the aggregate's effects on the pK a of oximes and on the rates of PNPDPP hydrolysis. All aggregates increased the rate of oximolysis of PNPDPP and the results were analyzed quantitatively. In particular, DODAC vesicles catalyzed the reaction and increased the rate of oximolysis of PNPDPP by IV several million fold at pH's compatible with pharmaceutical formulations. The rate increase produced by DODAC vesicles on the rate of oximolysis paraoxon by IV demonstrates the pharmaceutical potential of this system, since the substrate is used as an agricultural defensive agent and the surfactant is extensively employed in cosmetic formulations.

when a cosurfactant is added and, e.g., nematic phases can The influence of shear on a lamellar phase in the system sodium then be observed (5-7). dodecyl sulfate/decanol/water was investigated by combined rheo-Samples of macroscopic size are not homogeneously small angle light scattering. Three different regions were detected aligned, but usually a polydomain structure characterized by and all could be characterized by different scattering patterns in a nonuniform director orientation is observed. Shear flow depolarized and polarized light scattering. Flow alignment of anihas a profound effect on the structure and macroscopic alignsotropic domains in flow direction was found at low and high ment of liquid crystals, and consequently the rheological shear rates. A viscosity maximum was observed at intermediate properties of such materials are rather complex. Some studshear rates, and different anisotropic scattering patterns were deies on these rheological properties of lyotropic mesophases tected in polarized and depolarized scattering. The data are interpreted by a shear-induced formation of vesicles which displayed have been performed during the past years and have always a characteristic four-lobe pattern in depolarized scattering. A butreported complicated behavior (8-18). Since mechanical terfly pattern observed in polarized scattering indicated the exisdeformations can alter the structure, it is necessary to monitence of concentration fluctuations along the flow direction. The tor the structural changes during shear flow, to further undertransitions between the three regions were reversible, but the forstand the rheological properties of complex fluids. Different mation of vesicles was found only when the sample was sheared rheo-optical techniques such as small angle light scattering for a long time at appropriate shear rates. Complicated rheological (SALS) and small angle neutron scattering (SANS) or flow properties as, e.g., shear thinning and shear thickening, were found birefringence have been developed to study flow-induced as a consequence of the structural changes. ᭧ 1996 Academic Press, Inc. structural changes (19-30). Key Words: lyotropic lamellar phase; small angle light scatter-Shear alignment could be followed by simultaneous rheoing; shear; viscosity; vesicle.

Alicyclobacillus acidoterrestris, a thermoacidophilic, non-pathogenic and spore-forming bacterium has been detected in several spoiled commercial pasteurised fruit juices. A. acidoterrestris spores, besides being resistant to the pasteurisation treatment conditions normally applied to acidic fruit products, can germinate and grow causing spoilage. Therefore, this microorganism was suggested as the target to be used in the design of adequate pasteurisation processes. The objectives of this work were to investigate the influence of temperature (T: 85–97°C), total soluble solids (SS: 5–60°Brix or % by weight) and pH (2.5–6.0) on D-values (decimal reduction time) of Alicyclobacillus acidoterrestris (type strain, NCIMB 13137) spores, and to fit a model using response surface methodology. A central composite face-centred experimental design was used, and the response, D-value determined in malt extract broth, ranged between 0.498±0.045 and 94.9±6.7 min. Within the factor ranges studied, temperature was the parameter that most affected the D-value. Following this was the SS and, lastly, the pH value. A linear decrease in D-value was observed with decreasing SS and pH, and a non-linear decrease in D-value was noticed with increasing temperature. A second order polynomial was successfully fitted to the data (R2=0.98). In general, D-values measured in real fruit systems, such as orange, apple and grape juices, blackcurrant concentrates, cupuaçu (exotic fruit) extract and orange juice drink, were higher than those predicted by the malt extract broth model. This result emphasises the importance of experimental validation of any model-derived process.

The spontaneous formation of mixed vesicles, and their coexistence and solubilization due to the formation of mixed micelles have been investigated on the aqueous solutions of a mixed surfactant system constituted by two cationic surfactants: a C10-double-chain surfactant, didecyldimethylammonium bromide (di-C10DMAB), and a C12-single-chain surfactant, dodecylethyldimethylammonium bromide (C12EDMAB). The concentration at which the monomer-to-mixed vesicle transition occurs CVC*, as well

Background: Thalassemia is a hereditary hemolytic anemia caused by mutations in the globin gene complex. Circulatory disturbances including arterial and venous thrombosis have also been noted in these patients. Aggregability of abnormal RBC and the high level of membrane-derived microparticles stemming from activated platelets and other blood cells are thought to be responsible for the associated thrombotic risk. Destruction of RBC is also thought to be an important pathophysiological consequence, particularly through the formation of circulating vesicles. To our knowledge, there has been no attempt to quantitatively evaluate the number of RBC vesicles in thalassemia. This prompted us to study the level of RBC vesicles in the peripheral blood of thalassemia patients using quantitative flow cytometry.

Asymmetrical flow field-flow fractionation (AsFlFFF)/multi-angle light scattering (MALS) was employed for studying filter-extruded liposomes in carrier solutions with different ionic strength and osmolarity. By dilution of preformed liposome suspensions with different media, only the ionic strength in the external free aqueous phase was changed. Under such conditions the liposomes were found to elute at almost identical elution times, which is

During pregnancy, lymphocytes infiltrating the rabbit lacrimal gland disperse to the interacinar space from their normal focal concentrations, basal fluid secretion decreases, pilocarpine-induced fluid secretion increases, and stimulated fluid protein concentration decreases. Ductal epithelial cell prolactin (PRL) content increases and redistributes from the apical to the basal-lateral cytoplasm. A replication-incompetent adenovirus vector for rabbit PRL (AdPRL) was used to test the hypothesis that increased intracrine/autocrine PRL signaling alters secretory protein traffic in an ex vivo lacrimal acinar cell model. AdPRL had no discernable influence on microtubules or actin microfilaments or their responses to carbachol (CCh). Endogenous and transduced PRLs exhibited similar, nonpolarized, punctate distributions. Cells secreted PRL consititutively and at increased rates in response to CCh. In contrast, constitutive secretion of β-hexosaminidase was negligible, suggesting that the c...

Features that alter the glycolipid sugar headgroup accessibility at the membrane interface have been studied in bilayer lipid model vesicles using a fluorescence technique with the enzyme galactose oxidase. The effects on oxidation caused by variation in the hydrophobic moiety of galactosylceramide or the membrane environment for galactosylceramide, monogalactosyldiacylglycerol and digalactosyldiacylglycerol were studied. For this study we combined the galactose oxidase method for determining the oxidizability of galactose containing glycolipids, and the fluorescence method for determining enzymatic hydrogen peroxide production. Exposed galactose residues with a free hydroxymethyl group at position 6 in the headgroup of glycolipids were oxidized with galactose oxidase and subsequently the resultant hydrogen peroxide was determined by a combination of horseradish peroxidase and 10-acetyl-3,7dihydroxyphenoxazine (Amplex Red). Amplex Red reacts with hydrogen peroxide in the presence of horseradish peroxidase with a 1:1 stoichiometry to form resorufin. With this coupled enzyme approach it is also possible to determine the galactolipid transbilayer membrane distribution (inside-outside) in bilayer vesicles.

The dialysis of micellar and vesicular systems, through a cellulose acetate membrane permeable only to monomer surfactant, has been investigated for the system sodium decanoate/decanoic acid as a function of pH, in pH regions where micelles (pH 9) or vesicles (pH 7.5) are present. The results provide data that are helpful in establishing the thermodynamic state of the systems and the interplay of the relevant equilibrium and kinetic considerations. Additionally, the kinetics of spontaneous formation and destruction of vesicles when subjected to a pH-jump perturbation have been studied. Changes are rapid, taking place over a time scale of a few seconds.

Stable vesicles with diameters between about 1 and 10 Am were prepared by a particular emulsification technology that involved the use of the surfactants Span 80 and Tween 80 and the phospholipid lecithin (phosphatidylcholine from soybeans). Two membrane enzymes, Dfructose dehydrogenase from Gluconobacter sp. (FDH) and sarcosine dehydrogenase from Pseudomonas putida (SDH), were for the first time immobilized onto the bilayer membranes of these type of vesicles; and the catalytic activity and enzymatic stability were measured and compared with the enzymes in a vesicle-free solution. The enzyme activity as well as stability considerably increased upon immobilization. In particular, immobilized FDH at 25jC was stable for at least 20 days, while the activity of the free enzyme dropped to about 20% of its initial value during the same period of time.

Vesicle Water purification Sedimentation Sand filter Organic pollutants a b s t r a c t Vesicle-clay complexes in which positively charged vesicles composed of didodecyldimethylammonium bromide (DDAB) were adsorbed on montmorillonite removed efficiently anionic (sulfentrazone, imazaquin) and neutral (alachlor, atrazine) pollutants from water.

The rates of oximolysis of p-nitrophenyl diphenyl phosphate (PNPDPP) by Acetophenoxime; 10-phenyl-10-hydroxyiminodecanoic acid; 4-(9-carboxynonanyl)-1-(9-carboxy-1-hydroyiminononanyl) benzene; 1-dodecyl-2-[(hydroxyimino)methyl]-pyridinium chloride (IV) and N-methylpyridinium-2-aldoxime chloride were determined in micelles of N-hexadecyl-N,N,N-trimethylammonium chloride (CTAC), N-hexadecyl-N,N-dimethylammonium propanesulfonate and dioctadecyldimethylammonium chloride (DODAC) vesicles. The effects of CTAC micelles and DODAC vesicles on the rates of oxymolysis of O,O-Diethyl O-(4-nitrophenyl) phosphate (paraoxon) by oxime IV were also determined. Analysis of micellar and vesicular effects on oximolysis of PNPDPP, using pseudophase or pseudophase with explicit consideration of ion exchange models, required the determination of the aggregate's effects on the pKa of oximes and on the rates of PNPDPP hydrolysis. All aggregates increased the rate of oximolysis of PNPDPP and the results were analyzed quantitatively. In particular, DODAC vesicles catalyzed the reaction and increased the rate of oximolysis of PNPDPP by IV several million fold at pH's compatible with pharmaceutical formulations. The rate increase produced by DODAC vesicles on the rate of oximolysis paraoxon by IV demonstrates the pharmaceutical potential of this system, since the substrate is used as an agricultural defensive agent and the surfactant is extensively employed in cosmetic formulations. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1040–1052, 2009

Characterization of classical 'hand-shaken' moltilamellar lipid vesicles (MLVs) confirmed that these systems exclude solute during formation thus confounding previous captured volume measurements which typically have utilized solute as a marker of the ocduded aqueom~ space. We used solvent rather than solute to determine the captured volume of these systems and obtained values at least twice those previously reported. We present here a Valeted volume and lameHarity pmfde of 'hand-shaken' MLVs and suggest that these parameters are dependent on the lipid concentration present during hydration_.

Hollow structures on the submicrometer scale (nm) are obtained with the assembly of polyelectrolytes according to the layer-by-layer (LbL) technique. Following the LbL procedure, polymers alginate and chitosan were alternatively adsorbed on a vesicular template made of didodecyldimethylammonium bromide (DDAB). Evidence for the removal of the vesicular template entrapped in the alginate/chitosan film is presented. The removal of the vesicular template was achieved through interactions between a nonionic surfactant (Triton X100) and the double-chained surfactant forming the vesicles. The application of this approach allowed the production of hollow nanospheres with a mild procedure, avoiding the use of strong acids or other extreme working conditions that can modify the shell integrity. The obtained nanostructures were characterized by means of dynamic light scattering (DLS), the ζ potential, and scanning electron microscopy (SEM). The SEM analysis demonstrated the presence, after the core removal process, of nanocapsules indistinguishable in size and shape from the parent core-shell system. The analysis of the surface charge of the hollow nanocapsules, after the core dissolution, by ζ potential measurements, indicates good aggregate stability. DLS measurements showed that the size of the nanocapsules is on the order of hundreds of nanometers. Moreover, the size of both the core-shell and the hollow particles did not appear to be perturbed by variations in temperature or ionic strength.

Sustained release of neurotransmitter depends upon the recycling of synaptic vesicles. Until now, it has been assumed that vesicle recycling is regulated by signals from the presynaptic bouton alone, but results from rat hippocampal neurons reported here indicate that this need not be the case. Fluorescence imaging and pharmacological analysis show that a nitric oxide (NO) signal generated postsynaptically can regulate endocytosis and at least one later step in synaptic vesicle recycling. The proposed retrograde pathway involves an NMDA receptor (NMDAR)-dependent postsynaptic production of NO, diffusion of NO to a presynaptic site, and a cGMP-dependent increase in presynaptic phosphatidylinositol 4,5-biphosphate (PIP2). These results indicate that the regulation of synaptic vesicle recycling may integrate a much broader range of neural activity signals than previously recognized, including postsynaptic depolarization and the activation of NMDARs at both immediate and nearby postsynaptic active zones.

Periodontal disease is a localised inflammatory response caused by the infection of a periodontal pocket arising from the accumulation of subgingival plaque. Periodontal disease has been considered as a possible risk factor for other systemic diseases such as cardiovascular diseases and pre-term low birth weight infants. Advances in understanding the aetiology, epidemiology and microbiology of periodontal pocket flora have revolutionised the therapeutic strategies for the management of periodontal disease progression. This review summarises the recent developments in the field of intra-pocket drug delivery systems and identifies areas where further research may lead to a clinically effective intra-pocket delivery system. Periodontal disease is a collective term ascribed to several pathological conditions characterised by degeneration and inflammation of gums, periodontal ligaments, alveolar bone and dental cementum [1]. It is a localised inflammatory response caused by bacterial infection of a periodontal pocket associated with subgingival plaque [2]. Although bacteria are the primary cause of periodontal disease, the expression of microbial pathogenic factors alone may not be sufficient to cause periodontitis. Periodontal pathogens produce harmful by-products and enzymes that break extracellular matrices as well as host cell membranes to produce nutrients for their growth. In doing so, they initiate damage directly or indirectly by triggering host-mediated responses that lead to self-injury [1]. In the early phase of the disease (gingivitis), inflammation is confined to the gingiva but extends to deeper tissues in periodontitis, leading to gingival swelling, bleeding and bad breath. In the late phase of the disease, the supporting collagen of the periodontium is degenerated, alveolar bone begins to resorb and gingival epithelium migrates along the tooth surface forming a 'periodontal pocket' [2,3]. This periodontal pocket provides ideal conditions for the proliferation of microorganisms: primarily Gram negative, facultative anaerobic species. Prominent amongst these are Bacteroides spp.: B. intermedius and B. gingivalis; fusiform organisms: Actinobacillus actinomycetemcomitans, Wolinella recta and Eikenella spp.; and various bacilli and cocci; spirochetes; amoebas and trichomonads [2]. The periodontal pocket, however, remains and if it Reviews KEYNOTE REVIEW

Ketorolac loaded rigid and elastic vesicles were prepared by sonication and the physicochemical properties of the drug loaded-vesicle formulations were examined. Rigid and elastic vesicles were prepared from the double chain surfactant sucrose-ester laurate (L-595) and the single chain surfactant octaoxyethylene-laurate ester (PEG-8-L). Sulfosuccinate (TR-70) was used as a negative charge inducer. Evaluation of the prepared vesicle was performed by dynamic light scattering, extrusion and by (1)H NMR (T(2) relaxation studies). The vesicles mean size varied between 90 and 150 nm. The elasticity of the vesicles was enhanced with increasing PEG-8-L/L-595 ratio, while an increase in loading of ketorolac resulted in a reduction in vesicle elasticity. (1)H NMR measurements showed that the molecular mobility of ketorolac was restricted, which indicates that ketorolac molecules were entrapped within the vesicle bilayers. The T(2) values of the aromatic protons of ketorolac increased graduall...

Hemoglobin vesicles (HbV) as red cell substitutes were prepared from a purified carbonylhemoglobin (HbCO) solution and a lipid mixture composed of phospholipids, cholesterol, and R-tocopherol. The diameter was controlled to 251 (87 nm using an extrusion method; the vesicles penetrated through the membrane filters with regulated pore sizes. After the ligand exchanging reaction (HbCO f HbO 2), the oxygen affinity (P 50) of HbV was 32 Torr, which was controlled with the coencapsulation of pyridoxal 5′-phosphate. The rate of metHb formation in HbV was nonenzymatically reduced with the coencapsulation of DL-homocysteine. The Hb concentration of the HbV suspension, which was dispersed in a phosphate buffered saline solution (pH 7.4), was controlled at 10 g/dL. At this concentration, the total lipid concentration was 6.2 g/dL and the viscosity, 2.6 cP (230 s-1), was lower than that of the blood (4.4 cP). The HbV suspension showed a typical non-Newtonian flow for a particle dispersion and agreed well with the Casson model. The viscosity at shear rates lower than 23 s-1 showed a maximum with increasing the mixing ratio of human blood, plasma, or albumin, while no maximum was observed for the mixture with washed red blood cells. The aggregates of HbV are formed by interaction with plasma proteins, including albumin, while the aggregates reversibly dissociate at higher shear rate.

The properties of a new family of lipid-specific fluorescent probes, a fatty acid, a phosphatidylcholine and a sphingomyelin, bearing a 3-perylenoyl-labeled hydrophobic chain, are described. Perylenoyl-labeled lipids readily enter the lipid bilayer, the fluorophore being localized in the apolar region of the membrane. The perylenoyl fluorophore is characterized by a high quantum yield, its fluorescence parameters (hex 446 nm, 2k m 479-545 nm) permit to apply it as an acceptor of excitation energy from the 9-anthrylvinyl fluorophore used earlier for phospholipid labeling (Molotkovsky, Jul. G., Manevich, Y.M., Gerasimova, E.N., Molotkovskaya, I.M., Polessky, V.A. and Bergelson, L.D. (1982) Eur. J. . The anthrylvinyl-labeled lipids were shown to be capable to report phase segregation between the corresponding prototype lipids in model systems. The combined use of anthrylvinyl-and perylenoyl-labeled lipids opens additional possibilities for investigation of lipid-lipid and lipid-protein interactions in artificial and biological membranes. Perylenoyl-labeled lipids appeared also to be useful as fluorescent dyes in cytological studies.

Fabrication of vesicles with the diameter of 4-30 m was achieved by mixing hydrophobic nonionic surfactant (Span 65) with a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer (Pluronic P123) in aqueous solutions at room temperature. Ring-shaped structure of the Pluronic P123/Span 65 mixture assemblies was confirmed by fluorescence microscopy. The presence of internal aqueous phase in the Pluronic P123/Span 65 mixture assemblies was determined by measuring the entrapment efficiency of calcein using fluorescence spectroscopy. On the other hand, Pluronic P123/Span 60 mixture system formed wire-like assemblies but not vesicles.