Dipalmitoylphosphatidylcholine Liposomes Research Articles

Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin

Objective: We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer.Significance: The present study provides the useful information for development of noninvasive treatment of diabetes.Methods: Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin.Results: DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased.Conclusion: We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.

Effects of hydroxy-xanthones on dipalmitoylphosphatidylcholine lipid bilayers: A theoretical and experimental study

Xanthones and derivatives are natural active compounds whose interest has been increased due to its several pharmacological effects. In this work, effects of hydroxy-xanthones on the physicochemical properties of dipalmitoylphosphatidylcholine (DPPC) liposomes have been investigated in terms of lipid bilayer fluidity, by means of molecular dynamics simulations and temperature dependence of zeta potential studies. Experimental results predict, in good agreement with simulations, that xanthones are able to be incorporated into DPPC liposomes with certain localization, fluidizing the bilayer. Both effects, localization and fluidity were found to be dependent of the number of hydroxilic substituents of the xanthone and the lipid phase state.

Effect of the presence of cholesterol in the interfacial microenvironment on the modulation of the alkaline phosphatase activity during in vitro mineralization

Mineralization of the skeleton starts within cell-derived matrix vesicles (MVs); then, minerals propagate to the extracellular collagenous matrix. Tissue-nonspecific alkaline phosphatase (TNAP) degrades inorganic pyrophosphate (PPi), a potent inhibitor of mineralization, and contributes Pi (Phosphate) from ATP to initiate mineralization. Compared to the plasma membrane, MVs are rich in Cholesterol (Chol) (∼32%) and TNAP, but how Chol influences TNAP activity remains unclear. We have reconstituted TNAP in liposomes of dipalmitoylphosphatidylcholine (DPPC) or dioleoylphosphatidylcholine (DOPC) combined with Chol or its derivatives Cholestenone (Achol) and Ergosterol (Ergo). DPPC plus 36% sterols in liposome increased the catalytic activity of TNAP toward ATP. The presence of Chol also increased the propagation of minerals by 3.4-fold. The catalytic efficiency of TNAP toward ATP was fourfold lower in DOPC proteoliposomes as compared to DPPC proteoliposomes. DOPC proteoliposomes also increased biomineralization by 2.8-fold as compared to DPPC proteoliposomes. TNAP catalyzed the hydrolysis of ATP more efficiently in the case of the proteoliposome consisting of DOPC with 36% Chol. The same behavior emerged with Achol and Ergo. The organization of the lipid and the structure of the sterol influenced the surface tension (γ), the TNAP phosphohydrolytic activity in the monolayer, and the TNAP catalytic efficiency in the bilayers. Membranes in the Lα phase (Achol) provided better kinetic parameters as compared to membranes in the Lo phase (Chol and Ergo). In conclusion, the physical properties and the lateral organization of lipids in proteoliposomes are crucial to control mineral propagation mediated by TNAP activity during mineralization.

Interaction of Selected Phenylpropenes with Dipalmitoylphosphatidylcholine Membrane and Their Relevance to Antibacterial Activity.

The effect of structurally closely related phenylpropenes (PPs), estragole, anethole, eugenol, and isoeugenol, on the fluidity of dipalmitoyl phosphatidyl choline (DPPC) liposome membrane was investigated by DSC, Raman, and fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH). Liposomes were prepared by thin-film hydration method at various DPPC:PP molar ratios. The DPH anisotropy measurements of blank and PP-loaded liposomes were performed at 28, 41, and 50°C, which correspond, respectively, to gel phase, main transition temperature of DPPC, and liquid phase. The Raman images showed the formation of nano- and micrometric spherical multi-lamellar vesicles. All studied PPs exhibited a membrane fluidizing effect which was reinforced by the presence of phenolic hydroxyl group in eugenol and isoeugenol. The PPs interacted with the choline head group and the alkyl chains of DPPC membrane, wherein isoeugenol and anethole possessing the same C7-C8 position of the double bond in the propenyl side chain, incorporated deeply in the bilayer. Additionally, the PPs were analyzed for antibacterial activity against E. coli by macrobroth dilution method. Anethole and estragole were more efficient in inhibiting the bacterial growth than eugenol and isoeugenol. We conclude that the fluidizing effect of PPs on the membrane is a common mechanism that is not related to the hydrophobicity of the PP molecule. Besides, other target sites may be involved in PP antibacterial activity against Gram-negative bacteria. The greater hydrophobicity of these PPs may contribute to their penetrability through the outer bacterial membrane.

Impact of Surface-Active Guanidinium-, Tetramethylguanidinium-, and Cholinium-Based Ionic Liquids on Vibrio Fischeri Cells and Dipalmitoylphosphatidylcholine Liposomes

We investigated the toxicological effect of seven novel cholinium, guanidinium, and tetramethylguanidinium carboxylate ionic liquids (ILs) from an ecotoxicological point of view. The emphasis was on the potential structure-toxicity dependency of these surface-active ILs in aqueous environment. The median effective concentrations (EC50) were defined for each IL using Vibrio (Aliivibrio) fischeri marine bacteria. Dipalmitoylphosphatidylcholine (DPPC) liposomes were used as biomimetic lipid membranes to study the interactions between the surface-active ILs and the liposomes. The interactions were investigated by following the change in the DPPC phase transition behaviour using differential scanning calorimetry (DSC). Critical micelle concentrations for the ILs were determined to clarify the analysis of the toxicity and the interaction results. Increasing anion alkyl chain length increased the toxicity, whereas branching of the chain decreased the toxicity of the ILs. The toxicity of the ILs in this study was mainly determined by the surface-active anions, while cations induced a minor impact on the toxicity. In the DSC experiments the same trend was observed for all the studied anions, whereas the cations seemed to induce more variable impact on the phase transition behaviour. Toxicity measurements combined with liposome interaction studies can provide a valuable tool for assessing the mechanism of toxicity.

Mixed lipid/polymer nanostructures: From advanced materials to drug delivery systems

The aim of this investigation was to study the alterations of the physicochemical characteristics of L-α-phosphatidylcholine, hydrogenated (Soy) (HSPC) and dipalmitoyl phosphatidyl choline (DPPC) liposomes, caused by the incorporation of a poly (oligoethylene glycol acrylate)-b-poly(lauryl acrylate) (POEGA-PLA) block copolymer at different molar ratios. We used Dynamic and Electrophoretic Light Scattering to determine the size and the ζ-potential; imaging techniques for investigate the structure and Static Light Scattering for quantifying the fractal morphology of the prepared nanosystems in situ. The size of mixed nanostructures became smaller with the incorporation of the block copolymer into the lipid membrane. The size of the prepared nanosystems ranged between 50-80nm. The fractal dimension (df) decreased significantly with the incorporation of block copolymer into liposomal bilayers. The morphology of DPPC:POEGA-PLA mixed nanostructures (with df equal to 1.8) is open (more loose). On the other hand, the morphology of HSPC: POEGA-PLA (with df equal to 2.1) is more compact and dense. The molar ratio of the POEGA-PLA did not alter the morphology of the mixed nanostructures, expect from HSPC:POEGA-PLA system. Finally, we studied the drug loading properties of the mixed nanostructures in order to examine their properties as advanced Drug Delivery nanosystems.

The pore forming capacity of Sticholysin I in dipalmitoyl phosphatidyl vesicles is tuned by osmotic stress

The osmotic condition modulates the properties of liposomes, particularly those related to their stability and response to external agents such as membrane-active proteins or peptides. In a previous work, we have demonstrated that an osmotic shock can increase, per se, water influx/efflux and the exit of the fluorophore calcein entrapped in the aqueous pool of dipalmitoylphosphatidylcholine (DPPC) and DPPC:sphingomyelin (SM) large unilamellar vesicles (LUVs), suggesting a loss of integrity of the liposome bilayer. In the present work, we have extended our study in order to assess how an osmotic imbalance prior to or synchronous with the addition of a recombinant variant of the pore-forming toxin sticholysin I (rSt I) modifies its pore forming capacity in DPPC and DPPC:SM (1:1) LUVs. Our results conclusively show the capacity of hypotonic gradients to improve the pore forming capacity of rSt I molecules, even in pure DPPC liposomes, rendering pore-formation less dependent on the presence of sphyngomyelin. In fact, non-active toxins in DPPC liposomes become active by a hypotonic imbalance in a similar way to those containing SM as a second component.

The Influence of Natural and Model Forms of Humic Acids on the Dynamic Parameters of Model Membranes

Abstract In this paper the influence of humic acid concentrations extracted from Histosols (HA-A) and their model forms (HA-B) separated from humic substances commercially produced by Carl Roth GmbH + Co.KG on the dynamic properties of liposome membranes was determined. Differences in the quality of the humic acids (HA-A and HA-B) were determined by the 1HNMR and FTIR methods. Liposomes from the sonication of egg yolk lecithin (EYL) in an aqueous solution and synthetic Dipalmitoylphosphatidylcholine (DPPC) were used. Fluidity of liposome membranes was determined by the EPR technique with spin probes (TEMPO, 16DOIXYL). The electrical parameters of membranes were found using a Keithley 6517 electrometer. Our study showed significant differences in the influence of HA-A and HA-B on the membranes. In the bilayer membranes of the liposomes of HA-A admixture there was slightly more stiffening of the interior of the membrane in comparison to HA-B. A similar effect was observed in the surface layer of the liposome membranes. This difference is particularly evident for DPPC liposomes, however, the EYL liposomes admixture with HA-B slightly increased the fluidity of the surface layer. Electrical study confirmed this effect. The study shows that natural and model forms of humic acids differ in their effects on the activity of tested membrane models. The strong differences in the interaction of HA-A and HA-B on parameter F in DPPC liposomes can be result from the transport of humic acids connected to the metal ions inside the membranes (xenobiotics present in the environment).

Effect of anionic and cationic polyamidoamine (PAMAM) dendrimers on a model lipid membrane

In spite of the growing variety of biological applications of dendrimer-based nanocarriers, a major problem of their potential applications in bio-medicine is related to the disruption of lipid bilayers and the cytotoxicity caused by the aggregation processes involved onto cellular membranes. With the aim to study model dendrimer-biomembrane interaction, the self-assembly processes of a mixture of charged polyamidoamine (PAMAM) dendrimers and dipalmitoylphosphatidylcholine (DPPC) lipids were investigated by means of Zeta potential analysis, Raman and x-ray scattering. Zwitterionic DPPC liposomes showed substantially different behaviors during their interaction with negatively charged (generation G=2.5) sodium carboxylate terminated (COO– Na+) dendrimers or positively charged (generation G=3.0) amino terminated (−NH2) dendrimers. More specifically the obtained results evidence the sensitive interactions between dendrimer terminals and lipid molecules at the surface of the liposome, with an enhancement of the liposome surface zeta potential, as well as in the hydrophobic region of the bilayers, where dendrimer penetration produce a perturbation of the hydrophobic alkyl chains of the bilayers. Analysis of the SAXS structure factor with a suitable model for the inter-dendrimers electrostatic potential allows an estimation of an effective charge of 15 ǀeǀ for G=2.5 and 7.6 ǀeǀ for G=3.0 PAMAM dendrimers. Only a fraction (about 1/7) of this charge contributes to the linear increase of liposome zeta-potential with increasing PAMAM/DPPC molar fraction. The findings of our investigation may be applied to rationalize the effect of the nanoparticles electrostatic interaction in solution environments for the design of new drug carriers combining dendrimeric and liposomal technology.

Temperature-dependent bifurcation of cooperative interactions in pure and enriched in β-carotene DPPC liposomes

We examined the influence of temperature on lipid intermolecular interactions and the organization of bilayers within multilamellar dipalmitoylphosphatidylcholine (DPPC) liposomes. We also investigated the effect of 0.5 mol% β-carotene, a non-polar carotenoid, on the adhesive properties of these liposomes. Atomic force microscopy (AFM) and differential scanning calorimetry (DSC) were used to correlate the changes in the physical properties of the liposomal systems with their thermotropic behaviour. Using DSC we detected two transitions in pure DPPC vesicles and in those containing 0.5 mol% β-carotene. In both systems the pretransition occurred at 34.5(1)°C and the main phase transition at 41.4 °C during heating. Upon cooling, the temperatures of the pretransition and the main transition decreased by about 6 °C and 1 °C, respectively. Changes in enthalpy and entropy were also similar in the two investigated systems. Data obtained in parallel AFM force experiments show that the adhesive forces between the liposomal systems and AFM probe strongly depend on the loading rate. Moreover, their characteristic monotonic changes and discontinuities are sensitive to temperature. In the range of temperatures from 27 °C to 31 °C, i.e. below the temperature of phase transition from gel to ripple phase, the adhesive forces measured in a water environment are about an order of magnitude higher in the presence of β-carotene than in pure DPPC liposomes. The observed variable dependence of adhesion on the loading rate suggests that there are changes in the long- and short-range interactions between lipids, and that these may be related to the occurrence of some clustering effects. In addition, the simultaneous existence of different subphases was found in the gel phase of DPPC liposomes. The presence of β-carotene at a level of 0.5 mol% stimulates the structural reorganization of DPPC multilamellar vesicles and enhances the bifurcation phenomenon detected in these systems.

Immobilization of chlorophyll by using layer-by-layer technique for controlled release systems and photodynamic inactivation

The development of systems for the controlled release of drugs is important because they allow the control of drug absorption and tissue distribution and also can reduce local toxicity. This study aimed to assemble and characterize two types of release systems, consisting of layer-by-layer films obtained from poly(allylamine) hydrochloride with chlorophyll (PAH/CHL films) or chlorophyll incorporated into dipalmitoylphosphatidylcholine liposomes (PAH/Lip+CHL films). For these systems, the molecular aggregation, growth process, thermally stimulated desorption, wettability, and controlling release of CHL was studied by using UV–vis spectroscopy and wetting contact angle analysis. In addition, experiments of photodynamic inactivation using PAH/CHL or PAH/Lip+CHL films with a 633-nm laser light were performed and the susceptibility of Candida albicans (C. albicans) to this approach was examined. Fluorescence and atomic force microscopies were used to investigate the surface morphology after the application of the photoinactivation procedure. A redshift of the UV–vis spectrum associated to films when compared with the spectrum of the CHL solution indicated a molecular aggregation of CHL molecules in the films. The film growth process was determined by a nucleation and a growth of spheroids or rods for either PAH/Lip+CHL or PAH/CHL films, respectively. Thermally activated desorption experiments indicated that interactions between CHL and PAH (126kJ/mol) in PAH/CHL or between Lip+CHL and PAH (140kJ/mol) in PAH/Lip+CHL films may be governed by electrostatic interactions. The wettability of PAH/Lip+CHL films was larger than that for PAH/CHL films, which can be attributed to hydrophilic groups on the surface of the DPPC liposomes. Release experiments revealed that free CHL in PAH/CHL films was released more slowly than its partner incorporated into liposomes. After the photodynamic inactivation, results of survival fraction and fluorescence microscopy revealed that C. albicans presented similar susceptibility for the two kinds of films. AFM supported the fluorescence one suggesting that cell death of C. albicans may occur due to damages to its cell wall by C. albicans.

Influence of inhalation anesthetics on the chain-melting phase transition of DPPC liposomes. Near-infrared spectroscopy studies supported by PCA analysis

Near-infrared (NIR) spectroscopy was applied for the first time to study the chain-melting phase transition of a lipid bilayer wall of dipalmitoylphosphatidylcholine (DPPC) liposomes in the presence of different inhalation anesthetics (enflurene, halothane, isoflurane, and sevoflurane). A good agreement with the literature data referred to anesthetic/DPPC membranes studied by many other techniques showed that NIR could be applied to the studies of lipid membranes as an alternative to commonly used mean-infrared (MIR) method. Relations between the temperature of the lipid phase transition of doped DPPC liposomes and the anesthetic concentration were estimated. The potency of disturbance of the lipid phase transition was compared between studied anesthetics.

Biological Activity of Japanese Quince Extract and Its Interactions with Lipids, Erythrocyte Membrane, and Human Albumin.

The aim of the study was to determine in vitro biological activity of fruit ethanol extract from Chaenomeles speciosa (Sweet) Nakai (Japanese quince, JQ) and its important constituents (−)-epicatechin (EC) and chlorogenic acid (CA). The study also investigated the structural changes in phosphatidylcholine (PC) liposomes, dipalmitoylphosphatidylcholine liposomes, and erythrocyte membranes (RBC) induced by the extract. It was found that the extract effectively inhibits oxidation of RBC, induced by 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH), and PC liposomes, induced by UVB radiation and AAPH. Furthermore, JQ extract to a significant degree inhibited the activity of the enzymes COX-1 and COX-2, involved in inflammatory reactions. The extract has more than 2 times greater activity in relation to COX-2 than COX-1 (selectivity ratio 0.48). JQ extract stimulated growth of the beneficial intestinal bacteria Lactobacillus casei and Lactobacillus plantarum. In the fluorimetric method by means of the probes Laurdan, DPH and TMA-DPH, and 1H-NMR, we examined the structural changes induced by JQ and its EC and CA components. The results show that JQ and its components induce a considerable increase of the packing order of the polar heads of lipids with a slight decrease in mobility of the acyl chains. Lipid membrane rigidification could hinder the diffusion of free radicals, resulting in inhibition of oxidative damage induced by physicochemical agents. JQ extract has the ability to quench the intrinsic fluorescence of human serum albumin through static quenching. This report thus could be of huge significance in the food industry, pharmacology, and clinical medicine.

Thermodynamics of interaction between carbohydrates and unilamellar dipalmitoyl phosphatidylcholine membranes

The purpose of this study was to examine the direct effect of sucrose and sucralose on the main phase transition of dipalmitoyl phosphatidylcholine (DPPC) liposomes with differential scanning calorimetry, for use as potential cryopreservatives for cells. Because cells are typically treated directly with cryopreservatives and not thermally cycled to erase thermal history, we have focused on the impact that these sugars have on the main phase transition during the first heating and cooling cycles. The incorporation of sucrose appears to have very little effect on the phase behavior of DPPC liposomes except a broadening of the main phase transition. In contrast, sucralose leads to a drop in the transition peak temperature from 41.5 to 39.6 °C when there is 50 mol% sucralose present. Further increases in sucralose concentration result in the peak transition temperature gradually increasing again to 41.1 °C at 87 mol% sugar. This change is accompanied by decrease in the width of the transition, during heating, as well as increased hysteresis. This phenomenon may be due to a kosmotropic effect resulting in partial dehydration and interdigitation of the bilayer as the sucralose concentration is increased. These findings indicate that sucralose may be useful for the cryopreservation of cell membranes.

The Localization of Phenolic Compounds in Liposomal Bilayers and Their Effects on Surface Characteristics and Colloidal Stability.

The interactions with and effects of five chemically distinct, bioactive phenolic compounds on the lipid bilayers of model dipalmitoylphosphatidylcholine (DPPC) liposomes were investigated. Complementary analytical techniques, including differential scanning calorimetry (DSC) and phosphorus and proton nuclear magnetic resonance spectroscopy (NMR), were employed in order to determine the location of the compounds within the bilayer and to correlate location with their effects on bilayer characteristics and liposomal stability. As compared to the phenolic compounds localized in the glycerol region of the DPPC head group within the bilayer, which enhanced the colloidal stability of the liposomes, compounds located closer to the center of the bilayer reduced vesicle stability as a function of time. Molecules present in the upper region of liposomal DPPC acyl chains (C1-C10) inhibited liposomal aggregation and size increase, perhaps due to tighter packing of adjoining DPPC molecules and increased surface exposure of DPPC phosphate head groups. These data may be useful for designing liposomal systems containing hydrophobic phenols and other small molecules, selecting appropriate analytical methods for determining their location within liposomal bilayers, and predicting their effects on liposome characteristics early in the liposome formulation development process.

Tetra- and Penta-Cyclic Triterpenes Interaction with Lipid Bilayer Membrane: A Structural Comparative Study.

The effect of tetracyclic (cortisol, prednisolone, and 9-fluorocortisol acetate) and pentacyclic (uvaol and erythrodiol) triterpenes (TTPs) on the fluidity of dipalmitoyl phosphatidyl choline (DPPC) liposome membrane was investigated by differential scanning calorimetry, Raman spectroscopy, and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH). Liposomes were prepared in the absence and presence of TTPs at molar ratios DPPC:TTP 100:1, 100:2.5, and 100:10. All the studied TTPs abolished the pre-transition and modified the intensity of the Raman peak at 715cm(-1) proving the interaction of TTP molecules with the choline head group of phospholipids. An increase in the Raman height intensity ratios of the peaks I 2935/2880, I 2844/2880, and I 1090/1130, giving information about the ratio disorder/order of the alkyl chains, and a decrease of the main transition temperature demonstrated the interaction of TTPs with the alkyl chains. The tetracyclic TTPs produced broadening of the phase transition profile. Besides, a scarcely splitting of the main transition peak was obtained with prednisolone and 9-fluorocortisol acetate. The results of fluorescence depolarization of DPH showed that the studied molecules fluidized the liposomal membrane at 25, 41, and 50°C. Pentacyclic TTPs, being more hydrophobic than tetracyclic ones, demonstrated higher fluidizing effect than tetracyclic TTPs in the liquid crystalline phase suggesting a deeper incorporation in the lipid bilayer. The presence of a free polar head group at the ring D seems to control the TTP incorporation in the bilayer and consequently its effect on the membrane fluidity.

Selective quantitation of the incorporation of the immunomodulator α-galactosylceramide in liposomes using LC–MS/MS

α-Galactosylceramide (α-GalCer) is a synthetic glycosphingolipid that has been widely studied as a potential vaccine adjuvant and exhibits distinct immunoregulatory effects when incorporated into liposomes. The aim of this study was to utilise the high selectivity of liquid chromatography–tandem mass spectrometry (LC–MS/MS) to develop a validated method for quantitating α-GalCer incorporation into liposomes.To separate unincorporated α-GalCer, liposomes were pelleted by centrifugation, resuspended and mixed with the mobile phase to allow solubilisation of the liposome components. Separation of α-GalCer was achieved using a C8 column with a mobile phase consisting of 7:3 (v/v) ethanol:methanol with 0.5% formic acid and 10mM ammonium formate. The multiple reaction monitoring (MRM) mode for the triple quadrupole was used to measure the peak area of the m/z 858.74→696.69 transition, which is the change in mass of the α-GalCer molecule after detachment of the galactose group through fractionation. The method developed here demonstrated specificity for α-GalCer in the presence of other liposome components.The validated method was used to determine the incorporation of α-GalCer in dipalmitoylphosphatidylcholine (DPPC) liposomes at varying concentrations and to monitor the stability of liposomes containing α-GalCer during storage at 4°C during 30 days.

Properties of calcium carbonate precipitated in the presence of DPPC liposomes modified with the phospholipase A2

Small unilamellar dipalmitoylphosphatidylcholine (DPPC) vesicles of average diameter 119 nm were used as a template for calcium carbonate precipitation. The precipitation was carried out from CaCl2 and Na2CO3 solutions at room temperature 25 °C and physiological temperature 37 °C. Moreover, liposomes modified with the enzyme phospholipase A2 (PLA2) were also used as an organic matrix. The influence of liposomes on the precipitation of calcium carbonate has been investigated using scanning electron microscopy and X-ray diffraction measurements. The particles surface modification was evidenced using zeta potential measurements and thermogravimetric analysis. The obtained results show that the effect of DPPC vesicles on the CaCO3 precipitation is concentration dependent. The stability of vaterite increases with the increase in liposomes content in the solutions. At the liposomes concentration equal to 100 mg L−1 a mixture of precipitated vaterite and calcite is observed. The temperature increase weakens this effect. Moreover, the enzyme PLA2 action has no significant influence on the calcium carbonate precipitation in the presence of DPPC liposomes at both investigated temperatures.

Semi-solid fluorinated-DPPC liposomes: Morphological, rheological and thermic properties as well as examination of the influence of a model drug on their skin permeation

The goal of this study was to investigate the influence of an incorporated model drug on the skin permeation of the vehicle itself as it may affect the microstructure and properties of the applied formulation via molecular interactions. For this purpose, we performed skin permeation studies using liposomes prepared with F-DPPC, a monofluorinated analog of dipalmitoylphosphatidylcholine (DPPC), with and without sodium fluorescein (SoFl) serving as model drug. Interestingly, the liposome preparation with F-DPPC yielded semi-solid opalescent systems. Hence, a thorough characterization was accomplished beforehand by electron microscopy imaging, rheological and thermoanalytical experiments. Freeze-fracture electron microscopy images confirmed the existence of globular shaped vesicles in the F-DPPC preparations and oscillatory rheological measurements proved the viscoelastic properties of F-DPPC and F-DPPC+SoFl liposomes in contrast to the viscous characteristics of DPPC liposomes. Thermoanalytical measurements revealed an increased phase transition temperature Tm of about 50°C for F-DPPC and F-DPPC+SoFl liposomes compared to pure DPPC liposomes with a Tm of about 43°C. The similar Tm of F-DPPC+SoFl and F-DPPC liposomes as well as the similar skin permeation of the vehicle compound F-DPPC compared to its drug-free counterpart suggest an incorporation of sodium fluorescein into the aqueous core of F-DPPC liposomes.

Evaluation of testicular tissue of adult rats treated with cisplatin incorporated into the liposome

Cisplatin (CPL) is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. However, it causes serious side effects, especially on reproduction. In order to reduce the undesirable effects caused by many drugs, liposomes have been used as a good system for drug delivery. The aim of this study was to investigate, for the first time, the effects of CPL incorporated into the dipalmitoyl phosphatidylcholine liposome (DPPC) on the testicular tissue of adult Wistar rats. The animals (n = 20) were distributed into four experimental groups: (a) control (distillated water); (b) liposome (DPPC, 1 mL), (c) cisplatin incorporated into liposome (CPL/DPPC), and (d) CPL (8 mg/kg body weight). The animals received a single intraperitoneal injection and were killed 10 days after each treatment for histopathological analysis of testes. The results showed that the testicular histomorphometric parameters in rats of DPPC and CPL/DPPC groups were similar to those of the control group. Meanwhile, rats of the CPL-treated group showed a variety of morphological alterations, including atrophy of seminiferous tubules and presence of multinucleated cells in the germinal epithelium. The incorporation of CPL into the liposome had no influence on the testicular weight or any other stereological parameters, but it was beneficial in maintaining the body weight of the animals. In conclusion, the liposome suppressed the cytotoxic effects caused by cisplatin in the testes of rats, suggesting a possible use in chemotherapy against cancer to reduce the side effects seen on reproduction.