Liposome Solution Research Articles

Preparation and evaluation of inhalable S-allylmercapto-N-acetylcysteine and nintedanib co-loaded liposomes for pulmonary fibrosis

Orally marketed products nintedanib (NDNB) and pirfenidone (PFD) for pulmonary fibrosis (PF) are administered in high doses and have been shown to have serious toxic and side effects. NDNB can cause the elevation of galectin-3, which activates the NF-κB signaling pathway and causes the inflammatory response. S-allylmercapto-N-acetylcysteine (ASSNAC) can alleviate the inflammation response by inhibiting the TLR-4/NF-κB signaling pathway. Therefore, we designed and prepared inhalable ASSNAC and NDNB co-loaded liposomes for the treatment of pulmonary fibrosis. The yellow, spheroidal co-loaded liposomes with a particle size of 98.32±1.98 nm and zeta potential of -22.5 ± 1.58 mV were produced. The aerodynamic fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of NDNB were >50 % (81.14 %±0.22 %) and <5 μm (1.79 μm±0.06 μm) in the nebulized liposome solution, respectively. The results showed that inhalation improved the lung deposition and retention times of both drugs. DSPE-PEG 2000 in the liposome formulation enhanced the mucus permeability and reduced phagocytic efflux mediated by macrophages. ASSNAC reduced the mRNA over-expressions of TLR-4, MyD88 and NF-κB caused by NDNB, which could reduce the NDNB's side effects. The Masson's trichrome staining of lung tissues and the levels of CAT, TGF-β1, HYP, collagen III and mRNA expressions of Collagen I, Collagen III and α-SMA in lung tissues revealed that NDNB/Lip inhalation was more beneficial to alleviate fibrosis than oral NDNB. Although the dose of NDNB/Lip was 30 times lower than that in the oral group, the inhaled NDNB/Lip group had better or comparable anti-fibrotic effects to those in the oral group. According to the expressions of Collagen I, Collagen III and α-SMA in vivo and in vitro, the combination of ASSNAC and NDNB was more effective than the single drugs for pulmonary fibrosis. Therefore, this study provided a new scheme for the treatment of pulmonary fibrosis.

Can Nanobubble Ozone Liposomes Be A New Agent In The Fight Against Foodborne Infections?

In this study, a nanobubble ozone liposome solution containing 2% ZnCl2 was used. The aging tests were conducted according to the ASTM F 1980 [1] standards. The minimum inhibitory concentration (MIC) level of the nanobubble ozone liposome solution with 2% ZnCl2 was determined as 1.562 ppm for strains of Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) by the CLSI M07 A9 [2] standard test method. To assess the time-dependent antibacterial effect of the nanobubble liposome solution with 2% ZnCl2, the solution's efficiency at a concentration of 2000 ppm and for different time intervals was tested on strains of Salmonella enterica subsp. enterica (ATCC® 14028™) and Listeria monocytogenes (ATCC® 7644™). The results showed that the antibacterial activity of the strains of S. enterica subsp. enterica started at the end of the 10th minute and the solution was effective after 30 minutes. For strains of L. monocytogenes, it was observed that the activity started at the end of the 2nd minute and the product was effective after the 10th minute. According to the ASTM F 1980 standards, it was found that the nanobubble ozone liposome solution retained its effectiveness in one-year stability tests. As a result, the nanoparticle liposome solution, a new product, does not lose its stability and effectiveness for a long time, contrary to what is known. Although the half-life of gaseous ozone is as short as 20 minutes, the stability in the nanoparticle liposome solution has been determined as at least one year. Since nanoparticle liposome solution is a natural and slow-release product, nanobubble ozone liposome solution with 2% ZnCl2 may be used as a newly developed agent against contaminations in food processing facilities caused by biofilm-forming microorganisms through the use in disinfections of surfaces that are in direct contact with food products.

In vitro gastrointestinal digestion of marine oil emulsions and liposomal solutions: fate of LC-PUFAs upon lipolysis.

The bioaccessibility and bioavailability of dietary fatty acids depend on the lipid to which they are esterified, the organisation of theses lipids in water and their recognition by lipolytic enzymes. In this work, we studied the release of marine long-chain polyunsaturated fatty acids (LC-PUFA), depending on their presentation either in the form of phospholipids (PL) or triacylglycerol (TAG). Two formulations based on marine PL or TAG extracted from salmon heads (Salmo salar) were prepared. Lipolysis was first tested in vitro by using individual gastrointestinal lipases and phospholipases to identify the enzymes involved in the digestion. Second, the lipolysis of the prepared formulations by a combination of enzymes was tested under in vitro conditions mimicking the physiological conditions found in the GI tract, both in the stomach and in the upper small intestine, in order to evaluate digestibility of TAG and LC-PUFA-containing liposomes. The in vitro results showed that TAG emulsion was hydrolyzed by porcine pancreatic extracts (PPE) and pure pancreatic lipase (PPL) with its cofactor, colipase, and to a lesser extent by pancreatic-lipase-related protein 2 (PLRP2) and a gastric extract (RGE) containing gastric lipase while no hydrolysis was observed with purified pancreatic phospholipase A2 (PLA2) and carboxyl ester hydrolase (CEH). The PL substrate was found to be hydrolysed by PLA2, PPE and PLRP2. Their phospholipase activities on liposomes formulation was dependent on the presence of bile salts. Using a two-step in vitro digestion model, we measured the kinetics of fatty acid release from TAG and PL during the gastric and intestinal phases of digestion. The highest overall lipolysis level was obtained with liposomes (around 75%) during the intestinal phase while they were preserved during the gastric phase. The overall lipolysis level of TAG emulsion was lower (around 33%), while it started already in the gastric phase. In conclusion, liposomes appear as a better delivery system for intestinal absorption of LC-PUFA than TAG. In addition, their resistance to lipolysis under gastric condition can protect LC-PUFA and provide a gastric stable delivery system for other molecules.

Application of ensemble machine learning approach to assess the factors affecting size and polydispersity index of liposomal nanoparticles

Liposome nanoparticles have emerged as promising drug delivery systems due to their unique properties. Assessing particle size and polydispersity index (PDI) is critical for evaluating the quality of these liposomal nanoparticles. However, optimizing these parameters in a laboratory setting is both costly and time-consuming. This study aimed to apply a machine learning technique to assess the impact of specific factors, including sonication time, extrusion temperature, and compositions, on the size and PDI of liposomal nanoparticles. Liposomal solutions were prepared and subjected to sonication with varying values for these parameters. Two compositions: (A) HSPC:DPPG:Chol:DSPE-mPEG2000 at 55:5:35:5 molar ratio and (B) HSPC:Chol:DSPE-mPEG2000 at 55:40:5 molar ratio, were made using remote loading method. Ensemble learning (EL), a machine learning technique, was employed using the Least-squares boosting (LSBoost) algorithm to accurately model the data. The dataset was randomly split into training and testing sets, with 70% allocated for training. The LSBoost algorithm achieved mean absolute errors of 1.652 and 0.0105 for modeling the size and PDI, respectively. Under conditions where the temperature was set at approximately 60 °C, our EL model predicted a minimum particle size of 116.53 nm for composition (A) with a sonication time of approximately 30 min. Similarly, for composition (B), the model predicted a minimum particle size of 129.97 nm with sonication times of approximately 30 or 55 min. In most instances, a PDI of less than 0.2 was achieved. These results highlight the significant impact of optimizing independent factors on the characteristics of liposomal nanoparticles and demonstrate the potential of EL as a decision support system for identifying the best liposomal formulation. We recommend further studies to explore the effects of other independent factors, such as lipid composition and surfactants, on liposomal nanoparticle characteristics.

Preparation of Uniform Nano Liposomes Using Focused Ultrasonic Technology.

Liposomes are microspheres produced by placing phospholipids in aqueous solutions. Liposomes have the advantage of being able to encapsulate both hydrophilic and hydrophobic functional substances and are thus important mediators used in cosmetics and pharmaceuticals. It is important for liposomes to have small sizes, uniform particle size distribution, and long-term stability. Previously, liposomes have been prepared using a homo mixer, microfluidizer, and horn and bath types of sonicators. However, it is difficult to produce liposomes with small sizes and uniform particle size distribution using these methods. Therefore, we have developed a focused ultrasound method to produce nano-sized liposomes with better size control. In this study, the liposome solutions were prepared using the focused ultrasound method and conventional methods. The liposome solutions were characterized for their size distribution, stability, and morphology. Results showed that the liposome solution prepared using focused ultrasonic equipment had a uniform particle size distribution with an average size of 113.6 nm and a polydispersity index value of 0.124. Furthermore, the solution showed good stability in dynamic light scattering measurements for 4 d and Turbiscan measurements for 1 week.

Characterization of hutbak based papers activated with limonene for food packaging

Limonene has a great potential to create an active paper for citrus products. The aim of this study is first to encapsulate limonone by liposome method and cyclodextrin inclusion methods and second to characterize and measure antifungal activity of hutbak papers that have active properties. Active hutbak papers are produced by dipping method with free limonene solution (H-L), encapsulated limonene containing liposome solution (H-Lp), hydroxypropyl-beta-cyclodextrin/limonene inclusion complex solutions (H-HPβCD) and beta-cyclodextrin/limonene (H-βCD) inclusion complex solutions. The effects of the production methods on the physical properties of the papers were analyzed by tensile test and color analysis. The produced active papers were stored for 30 days at 4⁰C. The amount of limonene remaining in the papers and antifungal activity analyzes against P. digitatum and P. expansium were performed on intervals of storage. The highest limonene content values were determined in H-βCD samples. Only the H-HPβCD samples showed zone diameters according to the disk diffusion method.

Effect of liposome composition on β-blocker interactions studied by capillary electrokinetic chromatography.

Liposome capillary electrokinetic chromatography was used to investigate the interactions between three β-blockers of different hydrophobicity and various liposome solutions. The studied β-blockers comprised alprenolol, propranolol, and carvedilol. The composition of the liposome solutions, containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phos-phoethanolamine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine, and cholesterol in various molar ratios, was designed by a response surface methodology-central composite design approach. Subsequently, after conducting the liposome capillary electrokinetic chromatography experiments and determining the retention factors from the electrophoretic mobilities of the compounds, and further calculating the distribution coefficients, an analysis of variance was performed. After extracting the statistical models, optimal operational conditions were obtained based on the developed models. To further investigate the interactions between the β-blockers and the liposomes, nanoplasmonic sensing experiments were carried out on two different liposome systems. The overall results demonstrate the strong influence of cholesterol and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine on the distribution coefficients.

The protective effect of N-acetylcysteine against liposome and chitosan-induced cytotoxicity

Aim N-acetylcysteine (NAC) is an antioxidant used to moderate liposome and chitosan-induced cell cytotoxicity at their high concentrations. Methods Liposome and chitosan were prepared and characterised. The cytotoxicity effect of liposome with NAC-loaded liposome (liposome-NAC) and chitosan solution with chitosan solution containing NAC (chitosan-NAC) on the A549 cell line was compared. Results Particle size, zeta potential, and NAC drug release for liposome were 125.9 ± 8 nm, −34.7 ± 2.1 mV, and 51.1% ± 3%, respectively. Scanning electron microscope (SEM) and transmission electron microscope (TEM) indicated spherical shape of liposome. Encapsulation efficiency of liposome-NAC was 12% ± 0.98%. Particle size and zeta potential for chitosan solution were 361 ± 11.3 nm and 10.8 ± 1.52 mV. Stability storage study indicated good stability of chitosan and liposome. Cell viability of liposome-NAC and chitosan-NAC significantly was higher than liposome and chitosan at all four concentrations. Conclusions NAC has a protective effect against liposome and chitosan-induced cell toxicity.

Imaging Flow Cytometry for High-Throughput Phenotyping of Synthetic Cells.

The reconstitution of basic cellular functions in micrometer-sized liposomes has led to a surge of interest in the construction of synthetic cells. Microscopy and flow cytometry are powerful tools for characterizing biological processes in liposomes with fluorescence readouts. However, applying each method separately leads to a compromise between information-rich imaging by microscopy and statistical population analysis by flow cytometry. To address this shortcoming, we here introduce imaging flow cytometry (IFC) for high-throughput, microscopy-based screening of gene-expressing liposomes in laminar flow. We developed a comprehensive pipeline and analysis toolset based on a commercial IFC instrument and software. About 60 thousands of liposome events were collected per run starting from one microliter of the stock liposome solution. Robust population statistics from individual liposome images was performed based on fluorescence and morphological parameters. This allowed us to quantify complex phenotypes covering a wide range of liposomal states that are relevant for building a synthetic cell. The general applicability, current workflow limitations, and future prospects of IFC in synthetic cell research are finally discussed.

Polypropylene composite hernia mesh with anti-adhesion layer composed of PVA hydrogel and liposomes drug delivery system

Polypropylene (PP) mesh has been widely used in hernia repair as prosthesis material owing to its excellent balanced biocompatibility and mechanical properties. However, abdominal adhesion between the visceral and PP mesh is still a major problem. Therefore, anti-adhesive PP mesh was designed with poly(vinyl alcohol) (PVA) hydrogel and liposomes drug delivery system. First, PVA hydrogel coating was formed on the surface of PP mesh with freezing-thawing processing cycles (FTP). Subsequently, the lyophilized PVA10-c-PP was immersed in rapamycin (RPM)-loaded liposome solution until swelling equilibrated to obtain the anti-adhesion mesh RPM@LPS/PVA10-c-PP. It was demonstrated that the hydrogel coating can stably fix on the surface of PP mesh even after immersed in PBS solution at 37 °C or 40 °C for up to 30 days. In vitro cell tests revealed the excellent cytocompatibility and the potential to inhibit cell adhesion of the modified PP mesh. Moreover, the anti-adhesive effects of the RPM@LPS/PVA10-c-PP mesh was evaluated through in vivo experiments. The RPM@LPS/PVA10-c-PP mesh exhibited less adhesion than original PP mesh throughout the duration of implantation. At 30 days, the adhesion score of RPM@LPS/PVA10-c-PP mesh was 1.37 ± 0.75, however the original PP was 3 ± 0.71. Furthermore, the results of H&E and Masson trichrome staining proved that the RPM@LPS/PVA10-c-PP mesh showed slighter inflammation response and significant looser fibrous tissue surrounded the PP filaments as compared to the native PP. The current findings manifested that this type of RPM@LPS/PVA10-c-PP might be a potential candidate for anti-adhesion treatment. Data availabilityData will be made available on request.

Liposomal bupivacaine is both safe and effective when administered via local infiltration at surgical site and mesovarium for laparoscopic ovariectomy in mares.

Liposomal local anaesthetic solutions may provide extended-duration analgesia postoperatively but have not been assessed following intra-peritoneal local infiltration in any species. To evaluate two doses of 1.33% liposomal bupivacaine (LB) versus 0.75% bupivacaine HCL (BHCl) for analgesia following laparoscopic ovariectomy in mares. Prospective cohort study. Fifteen healthy Quarter Horse mares (age 2-20 years) with normal bilateral ovarian palpation and appearance were enrolled. Horses were restrained in standing stocks and administered an α-2 agonist, butorphanol, and flunixin meglumine, followed by a variable rate infusion of sedation with α-2 agonists. Bilateral paralumbar fossa ovariectomies were performed. Treatment with either 30 ml 0.75% BHCl followed by 20 or 40 ml LB 13.3% (LB20 and LB40) volume expanded with saline to 80 ml total (n=6/group) or 80 ml BHCl alone (n=3, BCHL) was infused around incision sites and each mesovarium (LB or BHCl) prior to ovariectomy. Horses were monitored for 72 h by physical examination, algometry, and pain scoring (composite pain scale by Bussieres et al., Horse Grimace Scale). Abdominocentesis with peritoneal fluid analysis was performed at 72 h. Analgesia achieved with all treatment protocols allowed completion of ovariectomy procedures. Pressure algometry scores were lower in BHCl-treated horses versus both LB groups overall. Pain scores were improved with LB-treated horses in a dose-dependent fashion (Horse Grimace Scale scores LB40 < LB20 < BHCL; composite pain scale scores LB40 < BHCL, LB20 < BHCL, BHCL, and LB20 did not differ). Peritoneal fluid total protein was lower in LB40 versus LB20 and BHCL horses. No complications from LB administration were appreciated. Small patient sample size, lack of follow-up past 72 h or histopathology. Analgesia duration was extended and pain scores improved postoperatively with LB versus BHCl in a dose-dependent fashion. Further clinical evaluation of extended-duration local anaesthetics in horses for improved postoperative pain management is warranted.

DEVELOPMENT AND EVALUATION OF METFORMIN LIPOSOME FORMULATIONS

This inquiry focuses on liposomes as its subject matter. Liposomes are an excellent means of increasing the period of time during which an impact is active from hours to months. In the current investigation, liposomal formulations of metformin hydrochloride were created and analysed by the researchers. Because its plasma half-life is much shorter than that of other drugs (t1/2 = 1.5 h), the patient has to take the drug more often in order to keep its concentration in steady state plasma. In this study, liposomal formulations of metformin were tested for drug entrapment, surface characterisation, in-vitro drug release investigations, release kinetics, and their underlying processes. Study concludes that the development of liposomal solutions of metformin hydrochloride was a fruitful endeavour.

Regulation of Nitric Oxide (NO) Release by Membrane Fluidity in Ruthenium Nitrosyl Complex-Embedded Phospholipid Vesicles.

Incorporating water-insoluble nitric oxide (NO)-releasing molecules into biocompatible vesicles may allow for the tunable control of NO release on a specific target site. In vesicles, membrane fluidity plays an important role and influences the final therapeutic efficiency of drugs loaded into the vesicles. Hence, we aimed to investigate the effect of lipid fluidity on the NO release behavior of the photo-controllable ruthenium nitrosyl (Ru-NO) complex. In this regard, a new photoactive ruthenium nitrosyl complex (L.Ru-NO) with amphiphilic terpyridine ligand was synthesized and characterized in detail. L.Ru-NO was incorporated with commercial phospholipids to form nanoscale vesicles L.Ru-NO@Lip. The photoactive {Ru-NO}6 type complex released NO in the organic solvent CH3CN and aqueous liposome solution by irradiating under low-intensity blue light (λ = 410 nm, 3 W). To demonstrate the effect of lipid structure and fluidity on NO release, four different liposome systems L.Ru-NO@Lip1-4 were prepared by using phospholipids such as DOPC, DSPC, DPPC, and DMPC having different chain lengths and saturation. The NO-releasing abilities of these liposomes in aqueous medium were studied by UV-vis spectrum, colorimetric Greiss, and fluorescent DAF assay. The results show that the rate of NO release could be easily tuned by varying the lipid fluidity. The effect of temperature and pH on NO release was also studied. Further, the complex L.Ru-NO and liposomes L.Ru-NO@Lip1 were assayed as an antibacterial agent against the strains of bacteria Escherichia coli and Staphylococcus aureus.

EthoLeciplex: a new tool for effective cutaneous delivery of minoxidil

This work designates EthoLeciplex, a vesicular system consisting of phospholipid, CTAB, ethanol and water, as an innovative vesicular system for cutaneous/transfollicular minoxidil (MX) delivery. MX-loaded EthoLeciplex was fabricated by one-step fabrication process. Formulations were designed to study the effects of drug/phospholipid ratio, CTAB/phospholipid ratio, and ethanol concentration on vesicular size, PDI, surface charge and EE%. The optimized formulation was characterized by in vitro release, drug/excipient compatibility, ex vivo skin permeability and safety. A size of 83.6 ± 7.3 to 530.3 ± 29.4 nm, PDI of 0.214 ± 0.01 to 0.542 ± 0.08 and zeta potential of +31.6 ± 4.8 to +57.4 ± 12.5 mV were observed. Encapsulation efficiency was obtained in its maximum value (91.9 ± 16.2%) at the lowest drug/phospholipid ratio, median CTAB/phospholipid and the highest ethanol concentration. The optimized formulation was consisted of 0.3 as drug/lipid ratio, 1.25 as CTAB/lipid ratio and 30% ethanol concentration and showed responses’ values in agreement with the predicted results. Differential scanning calorimetry studies suggested that EthoLeciplex existed in flexible state with complete incorporation of MX into lipid bilayer. The cumulative amount of MX permeated from EthoLeciplex, conventional liposome and ethanolic solution after 12 h were 36.3 ± 1.5 µg/ml, 21 ± 2.0 µg/ml and 55 ± 4.0 µg/ml respectively. Based on the remaining amount, the amount of MX accumulated in different skin layers can be predicted in descending order as follows; EthoLeciplex > conventional liposome > MX solution. EthoLeciplex produced marked disorder in the stratum corneum integrity and swelling with no features of skin toxicity. This new cationic system is a promising carrier for cutaneous/transfollicular drug delivery.

Porous Mg‐stabilized amorphous calcium carbonate as carrier for hydrophobic drugs

AbstractIn this work, we demonstrate that porous MgACC microspheres could be prepared in liposome solution containing zwitterionic and anionic lipids. We find that the lipid molecules incorporated into MgACC could be as high as 10 mass%. Because hydrophobic drugs are lipophilic, the porous MgACC has been exploited as the carriers of hydrophobic drugs. Using lecithin as the source of lipids and N‐(rhodamine‐6G)lactam‐ethylenediamine (R6GNCCN) as the model of hydrophobic drugs, the optimal loading capacity was found to be ca. 1.4 mass%. The release of R6GNCCN to a phosphate buffer at pH 7.4 was over 90% within 5 hr. The drug release profile could be attenuated by encapsulating the MgACC core by a CaP shell.

Multiscale Dynamics of Lipid Vesicles in Polymeric Microenvironment.

Understanding dynamic and complex interaction of biological membranes with extracellular matrices plays a crucial role in controlling a variety of cell behavior and functions, from cell adhesion and growth to signaling and differentiation. Tremendous interest in tissue engineering has made it possible to design polymeric scaffolds mimicking the topology and mechanical properties of the native extracellular microenvironment; however, a fundamental question remains unanswered: that is, how the viscoelastic extracellular environment modifies the hierarchical dynamics of lipid membranes. In this work, we used aqueous solutions of poly(ethylene glycol) (PEG) with different molecular weights to mimic the viscous medium of cells and nearly monodisperse unilamellar DMPC/DMPG liposomes as a membrane model. Using small-angle X-ray scattering (SAXS), dynamic light scattering, temperature-modulated differential scanning calorimetry, bulk rheology, and fluorescence lifetime spectroscopy, we investigated the structural phase map and multiscale dynamics of the liposome–polymer mixtures. The results suggest an unprecedented dynamic coupling between polymer chains and phospholipid bilayers at different length/time scales. The microviscosity of the lipid bilayers is directly influenced by the relaxation of the whole chain, resulting in accelerated dynamics of lipids within the bilayers in the case of short chains compared to the polymer-free liposome case. At the macroscopic level, the gel-to-fluid transition of the bilayers results in a remarkable thermal-stiffening behavior of polymer–liposome solutions that can be modified by the concentration of the liposomes and the polymer chain length.

Formulation and Evaluation of Ethosomal Gel and Non-ethosomal Gel of S.grandiflora Leaves

The numbers of products based on new drug delivery systems have considerably increased in the past few years, and this growth is projected to carry on in the future. These bio-pharmaceuticals present challenges to drug delivery system because of their different nature and difficulty in delivery through conventional routes. Therefore, further research will focus on the delivery of these complex molecules through different routes, including nasal, pulmonary, vaginal, rectal, etc. The intend of the study was to formulate and evaluate ethosomes of Sesbania grandiflora leaves which may transport the drug to targeted site more efficiently than marketed gel preparation and also overcome the problems related with oral administration of drug. Trans-dermal drug delivery is a technique which can be exploited to overcome the variables, which could affect the oral absorption of drugs such as pH, food intake and gastrointestinal motility. As compared to liposome or hydro-alcoholic solution ethosomal systems were much more capable at delivering a fluorescent probe to the skin in terms of quantity and depth. The formulations were prepared with ethanol, lecithin, propylene glycol, and glycerol and were evaluated. The lecithin (phospholipids) used as a vesicles forming component, polyglycol and ethanol used as a skin penetration enhancer. The drug released of formulated ethosomal gel was 4-5 times improved as compared to non ethosomal gel which directly achieves unparalleled flexibility in formulation. Ethosomal gel successfully addresses the issues relating to the drug delivery of poorly water-soluble drugs, peptides, potent drugs and the release of multi-drugs.

Preparation of organic-solvent free liposome of Piper albi Linn extract in solution and powder form

Piperine is bioactive alkaloid extracted from white pepper (Piper albi Linn) with several beneficial pharmacological activities. It is also known to enhance the bioavailability of several limited solubilities of other compounds such as curcumin and resveratrol. Nevertheless, due to its poorly water-soluble character, piperine and extract of white pepper are less applied among other plant extracts. Therefore, our research focussed on the engineering of white pepper extract standardized to piperine in liposome solution and liposome powder for further preparation of various pharmaceutical dosage forms.Our research in preparation of extracted white pepper in liposome delivery system successfully prepared spheric liposome solution with 98.92%±1.17% and an average size of 398.7 nm. The liposome was also successfully prepared in dry powder form with sucrose as a carrier for liposome protection. The rehydration is successfully forming a spheric shape with a similar profile to the initial liposome solution. This research paves the way for scalable white pepper extract liposome preparation without the utilization of toxic organic solvent, to produce the commercial solvent-free product in the future.Keywords: Piperine, Piper albi Linn, liposome, extract, organic solvent-free, drug delivery system, spray dry

Polydiacetylene-based colorimetric and fluorometric sensors for lead ion recognition.

Development of novel sensors for the detection of lead ions (Pb2+) has attracted increasing interest due to their inherent toxic effects on human health and the environment. In this study, we describe two new polydiacetylene (PDA)-based liposome sensors for the colorimetric and fluorometric recognition of Pb2+ in aqueous solution. In the sensor system, a thymine-1-acetic acid (TAA) or orotic acid (OA) group was reasonably introduced into the diacetylene monomer to work as a strong binding site for Pb2+. The TAA- or OA-functionalized monomer and 10,12-pentacosadiynoic acid (PCDA) were incorporated into PDA liposomes in aqueous solution. After UV light-induced polymerization, deep blue colored liposome solutions were obtained. Upon the addition of a series of transition metal cations into the liposome solutions, only Pb2+ could induce a color change from blue to red observable by the naked eye and a large fluorescence enhancement. The results clearly showed that the PDA–EDEA–TAA and PDA–EDEA–OA liposomes could act as highly selective and sensitive probes to detect Pb2+ in aqueous solution. The detection limits of PDA–EDEA–TAA and PDA–EDEA–OA systems are 38 nM and 25 nM, respectively. The excellent selectivity of PDA liposomes could be attributed to the stronger complexation behavior of Pb2+ with TAA (or OA) and the carboxylic acid at the lipid–solution interface which could perturb the PDA conjugated backbone. In addition, the proposed sensors were successfully applied to detect trace amounts of Pb2+ in real water samples with excellent recovery, indicating that the developed method had a good accuracy and precision for the analysis of trace Pb2+ in practical samples.

Nanobubble Ozone Stored in Hyaluronic Acid Decorated Liposomes: Antibacterial, Anti-SARS-CoV-2 Effect and Biocompatibility Tests.

PurposeSARS-CoV-2-infected individuals may be asymptomatic, and therefore, the virus is highly contagious. We aimed to develop an agent to control viral replication in the upper respiratory tract and to prevent progression of the disease into the lower airways as well as inter-individual transmission. For this purpose, we investigated the antibacterial and antiviral activities of our novel nanobubble ozonated hyaluronic acid-decorated liposomal (NOHAL) solution, developed by using nanotechnology.MethodsThe MIC levels of NOHAL solution were determined on blood agar cultures of Staphylococcus aureus (ATCC 6538), Streptococcuspneumoniae (ATCC 49619) and Escherichia coli (ATCC 25922). The in vitro anti-viral activity of NOHAL solution was studied using recombinant SARS-CoV-2 copies of the original virus, grown in Vero cells generated by reverse genetic technology. Human primary lung epithelial cells obtained by bronchoscopy or lung resection were used for cell viability tests using flow cytometry analysis. The cytotoxicity testing was performed using the BALB/c 3T3 (CCL-163) cell line. Skin, oral, nasal and ocular irritation tests were performed using New Zealand albino rabbits, Syrian hamsters, BALB c mice and New Zealand albino rabbits of both sexes.ResultsBacterial growth was prevented by NOHAL solution in a time-/dose-dependent manner. In vivo or in vitro experiments did not show any toxicity of NOHAL solution. No cytotoxicity was recorded on cell viability. No skin, oral, nasal or ocular toxicities were recorded. In addition, in a SARS-CoV-2 mouse infection model, NOHAL solution diminished the viral RNA levels effectively in nasopharyngeal and lung samples after its prophylactic intranasal application.ConclusionNOHAL solution has the potential to reduce or prevent the spread of SARS-CoV-2 through the nose and/or oral cavity. The clinical efficacy of this solution needs to be tested in order to determine its efficacy in the early phase of COVID-19.