Diameter Of Liposomes Research Articles

Determination of pH Effects on Phosphatidyl-Hydroxytyrosol and Phosphatidyl-Tyrosol Bilayer Behavior.

A robust method was developed to investigate the liposomal behavior of novel enzymatically-synthesized hydroxytyrosol and tyrosol phospholipids. Bilayer characteristic obtained by this method, including bilayer formation stability and adsorption properties, were explored using dynamic light scattering, zeta-potential measurements, and quartz crystal microbalance with dissipation monitoring (QCMD), respectively. Liposome diameters were found to typically increase from pH 5.5 to pH 10. Zeta potentials values, on the other hand, were found to be well below −25 mV at all pH conditions explored, with the lowest values (and thus, the best liposome stability) at pH 5.5 or pH 10. Quartz crystal microbalance with dissipation monitoring measurements demonstrated that 100% 1,2-dioloeoylphosphatidyl-hydroxytyrosol (DOPHT) liposomes adsorbed intact onto silica in buffer conditions at pH 5.5 and with no calcium, or at pH 7.5 with calcium (no adsorption was detected at pH 10). 1,2-Dioleoylphosphatidyl-tyrosol (DOPT) liposomes were shown to adsorb intact under buffer conditions only at pH 5.5 with and without calcium. 1,2-Dioleoylphosphatidyl-2-phenolethanol (DOPPE), in comparison, readily adsorbed intact at pH 7.5 without calcium and just slightly at pH 5.5 with calcium present, but formed a supported bilayer over hours at pH 5.5 in the absence of calcium ions.

A physicochemical study of ophthalmological vital dyes: From dimerization equilibrium in buffer solution to their liposomal dispersions

Vital dyes are used both in intra-operative and diagnostic ophthalmology as liquid solutions wherein dyes self-associate reducing their effects. Hence, an efficient dyes-delivery system is required to carry the maximum fraction of dye administered to the target site. In this study primarily two aspects of indocyanine green, patent blue V and brilliant blue G have been investigated. First, band profiles of UV–Vis absorption and emission spectra, acquired as a function of dye concentration in buffer solutions(pH = 7.4), have been analyzed to calculate the dimerization constant. Results demonstrate that their self-assembly properties have to be correlated to the molecular polarization. Second, the vital dyes have been loaded into liposomes prepared with the thin-film hydration method followed by extrusion. Encapsulation efficiency has been calculated to be 30%. Scanning electron microscopy and dynamic light scattering measurements have revealed that dye inclusion reduces the liposome diameter. Activation energy of liposome diffusion has been extracted by Arrhenius plots. Zeta potential measurements as a temperature function have been exploited to evaluate a dimensionless surface charge and prove that ratio charge(dye-loaded liposome)-to-charge(blank liposome) is always greater than unity and decreases with temperature.

Rapid optimization of liposome characteristics using a combined microfluidics and design-of-experiment approach.

Liposomes have attracted much attention as the first nanoformulations entering the clinic. The optimization of physicochemical properties of liposomes during nanomedicine development however is time-consuming and challenging despite great advances in formulation development. Here, we present a systematic approach for the rapid sizeoptimization of liposomes. The combination of microfluidics with a design-of-experiment (DoE) approach offers a strategy to rapidly screen and optimize various liposome formulations, i.e., up to 30 liposome formulations in 1day. Five representative liposome formulations based on clinically approved lipid compositions were formulated using systematic variations in microfluidics flow rate settings, i.e., flow rate ratio (FRR) and total flow rate (TFR). Interestingly, flow rate-dependent DoE models for the prediction of liposome characteristics could be grouped according to lipid-phase transition temperature and surface characteristics. For all formulations, the FRR had a significant impact (p < 0.001) on hydrodynamic diameter and size distribution of liposomes, while the TFR mainly affected the production rate. Liposome characteristics remained constant for TFRs above 8mL/min. The stability study revealed an influence of lipid:cholesterol ratio (1:1 and 2:1 ratio) and presence of PEG on liposome characteristics during storage. To validate our DoE models, we formulated liposomes incorporating hydrophobic dodecanethiol-coated gold nanoparticles. This proof-of-concept step showed that flow rate settings predicted by DoE models successfully determined the size of resulting empty liposomes (109.3 ± 15.3nm) or nanocomposites (111 ± 17.3nm). This study indicates that a microfluidics-based formulation approach combined with DoE is suitable for the routine development of monodisperse and size-specific liposomes in a reproducible and rapid manner.

Preclinical evaluation of thermosensitive poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-grafted liposomes for cancer thermochemotherapy

Thermosensitive liposomes grafted with cholesterol-conjugated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) (chol-pHPMAlac) have been developed for heat-induced release of doxorubicin (DOX). These liposomes release DOX completely during mild hyperthermia, but their interaction with blood cells and cancer cells has not been studied. Following intravenous administration, liposomes may interact with plasma proteins and various types of cells (e.g., endothelial cells, platelets, and macrophages), which would reduce their disposition in the tumor stroma. Interaction between liposomes and platelets may further cause platelet activation and thrombosis, which could lead to vascular occlusion and thromboembolic complications. The aim was to investigate DOX release kinetics in the presence of serum, stability, in vitro uptake by and toxicity to cancer cells and somatic cells, and platelet activating potential of the chol-pHPMAlac liposomes. DOX release was determined spectrofluorometrically. Liposome stability was determined in buffer and serum by dynamic light scattering and nanoparticle tracking analysis. Association with/uptake by and toxicity of empty liposomes to AML-12, HepG2 (both hepatocyte-derived cancer cells), RAW 264.7 (macrophages), and HUVEC (endothelial) cells was assayed in vitro. Platelet activation was determined by analysis of P-selectin expression and fibrinogen binding. DOPE:EPC liposomes (diameter = 135 nm) grafted with 5% chol-pHPMAlac (cloud point (CP) = 16 °C; Mn = 8.5 kDa) released less than 10% DOX at 37 °C in 30 min, whereas complete release took place at 47 °C or higher within 10 min. The size of these liposomes remained stable in buffer and serum during 24 h at 37 °C. Fluorescently labeled but DOX-lacking chol-pHPMAlac-liposomes exhibited poor association with/uptake by all cells under investigation, were not cytotoxic, and did not activate platelets in both buffered solution and whole blood. In conclusion, thermosensitive chol-pHPMAlac-grafted liposomes rapidly release DOX during mild hyperthermia. The liposomes are stable in a physiological milieu, are not taken up by cells that are encountered in an in vivo setting, and are non-antagonistic towards platelets. Chol-pHPMAlac-grafted liposomes are therefore good candidates for DOX delivery to tumors and temperature-triggered release in tumor stroma.

Impact of curcumin liposomes with anti-quorum sensing properties against foodborne pathogens Aeromonas hydrophila and Serratia grimesii

Quorum sensing (QS) is a signal sensing system by which bacteria monitor the density of their population, thus, targeting to QS system may be an alternative approach to control diverse cellular processes including the microbial contamination and the virulence of human and plant pathogens as bacteria have been evolving resistance to antibiotics. In this study, curcumin liposomes were prepared by film dispersion method to increase its bioavailability against QS systems of food-borne epathogenic bacteria, i.e. Aeromonas hydrophila and Serratia grimesii. And their physicochemical properties were measured including particle size, zeta-potential entrapment rate as well as drug-loading rate. Meanwhile, the effects of curcumin liposomes on QS phenomenon of food-borne pathogens including biofilm formation, extracellular protease, swimming motility et al. were determined. Results showed that the average diameter of curcumin liposomes was (207 ± 8.2) nm and the entrapment rate and drug-loading rate were 82.71% and 23.33%. The zeta-potential of curcumin liposomes were (−37 ± 1.56) mv. Curcumin liposomes showed uniform structures by scanning electron microscopy (SEM). The curcumin liposomes could significantly inhibit QS systems of the two pathogens and the biological availability of curcumin has been improved.

The Interaction of Water-Soluble Pillar[5]Arenes Containing Amide and Ammonium Fragments with Lipid Bilayer

The absence of toxic properties and genotoxic activity was shown for water-soluble pillar[5]arenes containing amide and ammonium fragments. There was no induced mutation associated with the substitution of base pairs in the Ames test. Using the methods of turbidimetry and transmitting electron microscopy (TEM), the interaction of the macrocycle with the surface of lipid bilayer in the liquid crystalline state was established. DLS detected the appearance of larger particles upon titration of liposome suspension with pillar[5]arene 3. TEM confirms an increase in the average diameter of liposomes in the presence of the macrocycle which may result from liposome fusion.

Preparation and pharmacokinetics of cefquinome sulfate liposomes in goats

We evaluated the pharmacokinetics of cefquinome sulfate (CEF) liposomes in eight healthy goats following intramuscular administration at 4 mg/kg. The average particle diameter of CEF liposomes prepared by the ethanol injection method was 335nm with a CEF entrapment efficiency of 69.56%. The elimination half-life (t1/2b) of CEF liposomes was 33.04h compared with 16.21 h for CEF injected without carrier (p less than 0.05). The area under the concentration curve (AUC) for CEF liposomes was approximately three-times greater than for CEF alone (P less than 0.05). The time-point of maximum plasma concentration of the drug (Tp) and the maximum plasma concentration (Cmax) were 4.38 h and 1.99 ìg/mL for CEF liposomes, compared with 1.86 h and 3.55 ìg/mL for CEF without carrier, respectively.

Chitosan-coated liposomes as delivery systems for improving the stability and oral bioavailability of acteoside

The stability and bioavailability of acteoside were improved by encapsulating it with liposomes and chitosan. The liposomes were characterized through transmission electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy, and their particle size, zeta potential, encapsulation efficiency (EE), in vitro release, storage stability and oral bioavailability were tested. Results showed that the particles were nanosized and spherical. The average diameter, zeta potential, EE and relative bioavailability (Frel) of the acteoside liposome (Ac-Lip) were 78.49 ± 1.44 nm, −4.93 ± 0.79 mV, 81.06 ± 3.48% and 217.62%, respectively. These parameters increased to 92.77 ± 2.99 nm, +19.65 ± 0.90 mV, 88.10 ± 5.36% and 442.84%, respectively, after the surface of Ac-Lip was coated with 2 mg/mL of chitosan (CS-Ac-Lip). In contrast to Ac-Lip, the CS-Ac-Lip showed a reduced in vivo release rate and enhanced storage stability. The chitosan coating increased the diameter, zeta potential, EE, in vivo release time, stability and bioavailability of the Ac-Lip, and the chitosan–liposome is a promising delivery system for transporting acteoside or other bioactive components.

Influence of Cationic Phosphatidylcholine Derivative on Monolayer and Bilayer Artificial Bacterial Membranes.

An increasing number of bacterial infections and the rise in antibiotic resistance of a number of bacteria species forces one to search for new antibacterial compounds. The latter facts motivate the investigations presented herein and are aimed at studying the influence of a cationic lipid, 1-palmitoyl-2-oleoyl- sn-glycero-3-ethylphosphocholine (EPOPC), on model (mono- and bilayer) membranes. The monolayer experiments involved the analysis of the interactions of EPOPC with bacterial membrane lipids in one component and mixed systems as well as Brewster angle microcopy studies. The properties of liposomes were analyzed based on the results of dynamic light scattering (DLS) and zeta potential measurements as well as on the experiments concerning the release of calcein entrapped in liposomes after titration with surfactant solution and steady-state fluorescence anisotropy of DPH. The obtained results evidenced that EPOPC, even at low concentrations, strongly changes organization of model systems making them less condensed. Moreover, EPOPC decreases the hydrodynamic diameter of liposomes, increases their zeta potential, and destabilizes model membranes, increasing their fluidity and permeability. Also, the in vitro tests performed on Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) strains prove that EPOPC has some bacteriostatic properties which seem to be stronger toward Gram-negative than Gram-positive bacteria. All these findings allow one to conclude that EPOPC mode of action may be directly connected with the interactions of EPOPC molecules with bacterial membranes.

Physical and chemical stability of anthocyanin-rich black carrot extract-loaded liposomes during storage

In this study, the protection effect of black carrot extract on the stability of liposomes during storage was evaluated. The physical and chemical stability of the extract (0.4% w/w) including extract-loaded liposomes with various lecithin content (1%, 2%, and 4% w/w) were demonstrated. Z-average particle diameter and zeta potentials of liposomes were evaluated before and after 21 days of storage. The particle diameter of the samples was found to be lower than 50 nm after storage and no statistical change was determined (p < 0.05). The liposomes with and without extract were visualized by transmission electron microscopy (TEM) after negative staining. The TEM images revealed that unloaded and extract-loaded liposomes are similar in size. The degradation of extract (30%–90%), phenolic content (10%–29%), and antioxidant capacity (4%–33%) of liposomes depending on lecithin content were also determined during storage to evaluate the biochemical stability. A hexanal analysis was performed to investigate the lipid oxidation in liposomes within 60 days. According to the results, the oxidation of polyunsaturated fatty acids may be inhibited with the addition of the extract to liposomes; however, lipid content should be limited according to the extract concentration. The highest protection on oxidation was observed in extract-loaded liposomes containing 1% lecithin. The study provided valuable data on the contribution of an anthocyanin addition to liposomes to overcome oxidation of unsaturated phospholipids.

Preparation and characterization of liposomes encapsulating Calophyllum inophyllum oil

Callophyllum inophyllum oil, also known as Tamanu oil, is reported to treat a wide range of skin problems such as acne, eczema, psoriasis, herpes, hemorrhoids, and injuries caused due to wounds, among others. Liposomes, which are effective carriers for topical treatment of dermal diseases, could enhance the therapeutic efficiency of Tamanu oil. Therefore, the purpose of this study was to formulate and characterize liposomes loading Tamanu oil. Liposomes encapsulating Tamanu oil with different ratios of Phospholipon 90G and L-α-lecithin were prepared using the thin-film hydration technique. Liposomal formulations were characterized in terms of aspect, particle size, size distribution, zeta potential, and morphology by using light microscope and dynamic light scattering analysis (DLS). Furthermore, the best formulation was tested with the storage stability after 30 days, and Tamanu oil loaded in the liposomes was identified as dictated in Vietnamese pharmacopoeia. The data demonstrated that an average liposome diameter of 53 nm with a narrow polydispersity (0.289) was obtained at a Phospholipon 90G to L-α-lecithin molar ratio of 4:6, and a Tamanu oil to phospholipid mass ratio of 1:3 approximately. In addition, according to the DLS results, the particle size and the zeta potential were quite stable at 2-8oC during 30 days of storage. The study achieved the promising results for developing a novel formulation containing Tamanu oil, which may be valuable to treatment of skin diseases.

Mechanical properties of milk sphingomyelin bilayer membranes in the gel phase: Effects of naturally complex heterogeneity, saturation and acyl chain length investigated on liposomes using AFM

Sphingomyelin (SM) molecules are major lipid components of plasma membranes that are involved in functional domains. Among natural SMs, that found in milk (milk-SM) exhibits important acyl chain heterogeneities in terms of length and saturation, which could affect the biophysical properties and biological functions of the milk fat globule membrane or of liposome carriers. In this study, the thermotropic and mechanical properties of milk-SM, synthetic C16:0-SM, C24:0-SM and the binary mixtures C16:0-SM/C24:0-SM (50:50% mol) and C24:0-SM/C24:1-SM (95:5% mol) bilayer membranes were investigated using differential scanning calorimetry and atomic force microscopy, respectively. Results showed that acyl chain length, heterogeneity and unsaturation affected i) the temperature of phase transition of SM bilayers, and ii) the mechanical properties of liposome (diameter<200nm) membranes in the gel phase, e.g. the Young modulus E and the bending rigidity kC. This study increases our knowledge about the key role of naturally complex lipid compositions in tailoring the physical properties of biological membranes. It could be also used in liposomes development e.g. to select the suitable lipid composition according to usage.

Preparation of liposome bearing disulfide proteinoid and its reduction-responsive release property

Egg phosphatidylcholine (Egg PC) liposome bearing a disulfide proteinoid exhibited a reduction-responsive release property. Proteinoid composed of Asp, Leu, and cystamine (Prot(ALC)) and Asp and Leu (Prot(AL)) were synthesized by thermal condensation, confirmed by Raman, FT-IR, 1H NMR and 13C NMR spectroscopy. Egg PC liposome bearing the proteinoid was prepared by a film hydration and sonication method. The fluorescence quenching of dye (i.e. calcein) loaded in liposome bearing the proteinoid was 68.1–78.1%. The mean hydrodynamic diameter of liposome bearing the proteinoid was less than 200 nm and it decreased with increasing amount of the proteinoid. On the TEM photo, multi-lamellar vesicles were observed and the vesicle diameter was 100–300 nm. At all the phospholipid to proteinod ratios tested (i.e. 1:0.01, 1:0.02, and 1:0.05 (w/w)), the release degree in 12 h of dye loaded in liposome bearing Prot(AL) was less than 2%, and it was almost the same regardless of dithiothreitol (DTT, a reducing agent) concentration (i.e. 0, 10, and 20 mM). Whereas the release degree of dye loaded in liposome bearing Prot(ALC) was 1.5–8.4% and it was significantly dependent on DTT concentration.

Operative Parameters Optimization Production of Liposomes for the Encapsulation of Hydrophilic Compounds Using a New Supercritical Process

Liposomes are spherical vesicles formed by a inner aqueous core and a double lipidic layer around it. Conventional techniques for the production of liposomes are characterized by several drawbacks, like the production of micrometric vesicles, a difficult control of the Particle Size Distribution (PSD) and low encapsulation efficiencies (EE) of hydrophilic compounds. Many supercritical semi-continuous techniques were proposed in literature. They are successful in the intent of producing liposomes of smaller diameter, but the EE of hydrophilic compounds and the reproducibility are still a challenge. For this reason, it was recently proposed a new supercritical process whose aim is to invert the steps of production of liposomes, by first creating water droplets and then to fast surround them by phospholipids. We discovered that the high diffusion coefficient of phospholipids in supercritical carbon dioxide allows a fast coverage of water droplets preserving the drug content into the liposome core. In this work, hydrophilic compounds were encapsulated in the vesicles produced using SuperLip, such as Fluorescein, Bovine Serum Albumin (BSA) and Ampicillin, obtaining monodispersed spherical vesicles with a mean size from 100 to 300 nm. Operative parameters like water flow rate and lipid to water mass ratio were optimized. The EEs were evaluated with UV-Vis spectroscopy according to methods reported in literature, and obtaining high values up to 99 % for the three investigated compounds.

Fractional laser-assisted percutaneous drug delivery via temperature-responsive liposomes

Liposomes are used for transdermal delivery of drugs and vaccines. Our objective was to develop temperature-responsive (TR) liposomes to achieve temperature-dependent, controlled release of an encapsulated drug, and use fractional laser irradiation to enhance transdermal permeability of these liposomes. TR-liposomes prepared using a thermosensitive polymer derived from poly-N-isopropylacrylamide, N,N-dimethylacrylamide, egg phosphatidylcholine, and dioleoylphosphatidylethanolamine, delivered fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as a model drug. Effect of temperature on liposome size and drug release rate was estimated at two temperatures. Transdermal permeation through hairless mouse skin, with and without CO2 fractional laser irradiation, and penetration into Yucatan micro-pig skin were investigated using Franz cell and fluorescence microscopy. Dynamic light scattering showed that mean liposome diameter nearly doubled from 190 to 325 nm between 37 and 50 °C. The rate and amount of OVA-FITC released from TR-liposomes were higher at 45 °C that those at 37 °C. Transdermal permeation of OVA-FITC across non-irradiated skin from both TR- and unmodified liposomes was minimal at 37 °C, but increased at 45 °C. Laser irradiation significantly increased transdermal permeation of both liposome groups at both temperatures. Fluorescence microscopy of frozen biopsy specimens showed deeper penetration of FITC from unmodified liposomes compared to that from polymer-modified liposomes. Rhodamine accumulation was not observed with polymer-modified liposomes at either temperature. Temperature-dependent controlled release of an encapsulated drug was achieved using the TR-liposomes. However, TR-liposomes showed lower skin permeability despite higher hydrophobicity. Fractional laser irradiation significantly increased the transdermal permeation. Additional studies are required to control liposome size and optimize transdermal permeation properties.

A Novel Approach on Drug Delivery: Investigation of A New Nano-Formulation of Liposomal Doxorubicin and Biological Evaluation of Entrapped Doxorubicin on Various Osteosarcoma Cell Lines.

Objective In this study we prepared a novel formulation of liposomal doxorubicin (L- DOX). The drug dose was optimized by analyses of cellular uptake and cell viability of osteosarcoma (OS) cell lines upon exposure to nanoliposomes that contained varying DOX concentrations. We intended to reduce the cytotoxicity of DOX and improve characteristics of the nanosystems. Materials and Methods In this experimental study, we prepared liposomes by the pH gradient hydration method. Various characterization tests that included dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo-TEM) imaging, and UV- Vis spectrophotometry were employed to evaluate the quality of the nanocarriers. In addition, the CyQUANT® assay and fluorescence microscope imaging were used on various OS cell lines (MG-63, U2-OS, SaOS-2, SaOS-LM7) and Human primary osteoblasts cells, as novel methods to determine cell viability and in vitro transfection efficacy. Results We observed an entrapment efficiency of 84% for DOX within the optimized liposomal formulation (L-DOX) that had a liposomal diameter of 96 nm. Less than 37% of DOX released after 48 hours and L-DOX could be stored stably for 14 days. L-DOX increased DOX toxicity by 1.8-4.6 times for the OS cell lines and only 1.3 times for Human primary osteoblasts cells compared to free DOX, which confirmed a higher sensitivity of the OS cell lines versus Human primary osteoblasts cells for L-DOX. We deduced that L- DOX passed more freely through the cell membrane compared to free DOX. ConclusionWe successfully synthesized a stealth L-DOX that contained natural phospholipid by the pH gradient method, which could encapsulate DOX with 84% efficiency. The resulting nanoparticles were round, with a suitable particle size, and stable for 14 days. These nanoparticles allowed for adequately controlled DOX release, increased cell permeability compared to free DOX, and increased tumor cell death. L-DOX provided a novel, more effective therapy for OS treatment.

Ca2+-dependent aggregation and permeabilization of erythrocytes by ω-hydroxypalmitic and α, ω-hexadecandioic acids

This paper presents the data and describes the Ca2+-dependent effect of the products of ω-oxidation of palmitic acid, as well as ω-hydroxypalmitic and α, ω-hexadecandioic acids, on rat erythrocytes. It is shown that in the presence of Ca2+ these acids induce aggregation of erythrocytes, which is accompanied by a reduction in the number of single cells in suspension. As well, a release of K+ from the cells occurs, which indicates the permeabilization of the plasma membrane. However, ω-hydroxypalmitic and α, ω-hexadecandioic acids are inferior to palmitic acid in their ability to induce Ca2+-dependent erythrocyte permeabilization. Bovine serum albumin and blood serum inhibit the effects of palmitic acid. At the same time, the influence of these agents on the effects of ω-hydroxypalmitic and α, ω-hexadecandioic acids appears to be much weaker. It is shown that ω-hydroxypalmitic and α, ω-hexadecandioic acids in the presence of Ca2+ induce an increase in the hydrodynamic diameter of single-walled lecithin liposomes, which indicates their fusion and (or) aggregation. The mechanisms of ω-hydroxypalmitic acid/Ca2+- and α, ω-hexadecandioic acid/Ca2+-induced effects on rat erythrocytes are discussed.

In vitro anti-inflammatory efficacies of liposomal suspensions of acetylsalicylic acid

Egg phosphatidylcholine (EPC) liposome containing acetylsalicylic acid (ASA) (EPC/ASA liposome) was prepared by a film hydration and sonication method, and the effect of liposome on the in vitro anti-inflammatory efficacy and the in vitro skin permeation of ASA was investigated. The mean diameter of EPC liposome and EPC/ASA liposome was about 271 and 175 nm, respectively. Both of liposomes were multi-lamellar vesicles on transmission electron microscopy photos. The in vitro viability of cell (Raw264.7) treated with EPC/ASA liposome suspension was significantly lower than the viability of cell treated with ASA solution. The amount of nitrite and prostaglandin E2 produced by cell treated with EPC/ASA liposome suspension was significantly lower than the amount produced by cells treated with ASA solution, indicating EPC liposome boosted the anti-inflammatory efficacy of ASA. The amount of ASA permeated through hairless mouse skin was inappreciable for 24 h when ASA solution was applied, whereas the permeation amount markedly increased to about 185 μg/cm2 for 24 h when EPC/ASA liposome suspension was applied. EPC liposome also enhanced the permeation into stratum corneum and epidermis/dermis.

Novel resveratrol delivery systems based on alginate-sucrose and alginate-chitosan microbeads containing liposomes

We reported the design of liposome-loaded Ca-alginate microspheres as a drug delivery system for controlled release of resveratrol. The effect of admixed sucrose and chitosan coating was assessed in terms of physicochemical, thermal and release properties of liposome-in alginate systems with encapsulated resveratrol. The diameter of liposomes produced by proliposome method increased from 412 to 471 nm with addition of sucrose as a cryoprotectant. DSC analysis revealed that phospolipids interact with each other while forming the lipid bilayer and that resveratrol was incorporated within the lipid bilayer, causing destabilizing effect in the two temperature regions (137–202 °C and 240–270 °C). Liposomes were entrapped within polymer network and remained intact as determined by SEM cross-sectional observation of the microbeads. Liposomes interfered with the thermal behavior of alginate in the temperature region above 220 °C. The presence of liposomes decreased the strength of the beads in comparison to placebo beads, according to mechanical tests on compression. Release studies performed in Franz diffusion cell showed the overall resistance to mass transfer one order of magnitude higher (106 s/m) than the resistance ascribed solely to the liposomal membrane. The chitosan coating, visible as a dense surface layer (∼7 μm thick) in dry state, caused decrease in encapsulation efficiency of resveratrol (85% vs. 91%) and in size of the particles (d50 of 387 vs. 440 μm); the chitosan also caused weakening of the polymer matrix, but increased resistance to drug diffusion (11.4 × 105 s/m) in comparison to the uncoated alginate-liposome formulation (9.1 × 105 s/m).

PH- and cinnamic acid-triggerable dioleoylphophatidylethanolamine liposome bearing polyethyleneimine/palmitic acid mixture

ABSTRACTpH and cinnamic acid (CA)-triggerable liposome was prepared by stabilizing dioleoylphosphatidylethanolamine (DOPE) bilayer with polyethyleneimine (PEI)/palmitic acid (PA) mixture. PEI/PA mixture was air/water interface-active, possibly due to the formation of PEI/PA salt conjugate. When the weight ratio of DOPE to PEI/PA mixture was 200:1, 100:1, 50:1, and 20:1, the fluorescence quenching degree of calcein loaded in the DOPE/PEI/PA assembly prepared using PBS (10 mM, pH 7.4) was 70.7%, 68.7%, 35.3%, and 14%, respectively, indicating that DOPE could be assembled into liposome at the physiological pH value with the aid of the PEI/PA mixture. The hydrodynamic mean diameter of liposome increased from 289 nm to 702 nm on increasing the weight ratio of the DOPE to PEI/PA mixture, possibly because of the bulky PEI chains. The release degree in 120 seconds at pH 4.5, pH 6.0, pH 7.4, and pH 9.0 was about 85%, 24.1%, 10.1%, and 62.0%, respectively, when the suspension of liposome of which the DOPE to PEI/PA mixture weight ratio was 50:1 (pH 7.4) was injected into the release medium of different pH values. The triggered release upon the acidification (i.e., pH 7.4–4.5) and the alkalization (i.e., pH 7.4–9.0) was possibly because PA and PEI were deionized under acidic and alkali conditions, respectively; thus the salt bridge of PEI/PA conjugate could break down. The DOPE liposome also exhibited CA-triggered release. The release degree in 120 seconds at 25°C was 23.1% and it was higher than the release degree at 50°C, 10.9%, possibly because CA could render PEI chains condensed and assembled under upper the critical solution temperature.