Stability Of Liposomes Research Articles

Alpha-Tocopherol-Infused Flexible Liposomal Nanocomposite Pressure-Sensitive Adhesive: Enhancing Skin Permeation of Retinaldehyde

Retinaldehyde (RAL), or retinal, is a vitamin A derivative that is widely used for several skin conditions. However, it is light sensitive and has low water solubility, limiting its efficiency in transdermal delivery. This study developed a novel delivery system for retinal (RAL) using flexible liposomes (FLPs) infused with α-tocopherol succinate (α-TS) to improve stability, and enhance skin permeability. The RAL-FLPs were embedded in pressure-sensitive adhesive (PSA) hydrogels, creating a delivery platform that supports prolonged skin residence and efficient permeation of RAL. The stability and skin permeation as well as human skin irritation and adhesion capabilities were assessed to determine the formulation’s safety and efficacy. Our findings suggested that the addition of α-TS could improve liposomal stability and RAL chemical stability. Moreover, the skin permeation and fluorescence microscopic-based studies suggested that the addition of α-TS could enhance skin permeability of RAL through hair follicles. The RAL-FLP was embedded in PSA hydrogels fabricated from 25% GantrezTM S-97 (GT) and 1% hyaluronic acid (Hya) with aluminum as a crosslinker. The PSA hydrogel exhibited desirable peeling and tacking strengths. The developed hydrogels also demonstrated greater skin deposition of RAL compared with its aqueous formulation. Additionally, the RAL-FLP-embedded PSA hydrogels showed no skin irritation and maintained better adhesion for up to 24 h compared to commercial patches. Hence, the developed hydrogels could serve as a beneficial platform for delivering RAL in treating skin conditions.

Preparation and Characterization of Universal Liquid Proliposomes Encapsulating Water-soluble Efficacious Substances.

Liposomes were extensively used for cosmetics and pharmaceuticals due to their versatility, biocompatibility, and biodegradability, as well as the ability to encapsulate water-soluble and fat-soluble substances. However, some challenges remain unsolved, including poor stability, complex preparation process, limited encapsulation efficiencies (EE%) and drug loading capacity (DLC%). We herein prepared universal liquid proliposomes by rotary evaporation method and optimized formulations with different pH, glycerol content, ethanol content and preparation process. The EE% of water-soluble substances was above 85%, and the maximum DLC% was 37.5%. In 7 different conditions, the optimal formulation of the proliposomes remained stable over 60 days. The excellent stability of proliposomes and nicotinamide liposomes and their essence, when applied to cosmetic formulations, was confirmed by the Turbiscan stability analyzer. The proposed universal liquid proliposomes can form liposomes encapsulating a variety of water-soluble substances rapidly, making them an accessible and versatile tool for improving the stability and applicability of water-soluble raw materials.

Antiaging synergistic effect in noninvasive transdermal delivery of peptide loaded liposomes by low energy/frequency radiofrequency

Low energy/frequency radiofrequency (LRF) combined with the transdermal delivery of liposome (L) encapsulated antiaging peptides technology is a remarkable, newly developed physical noninvasive transdermal penetration technique; it is considered a highly efficient, comprehensive and safe technology. In this study, our objective was to evaluate the physical and chemical mechanisms underlying the efficacy of this innovative technique involving a combination of LRF and L, termed LLRF, that exerts a synergistic anti-aging effect on human skin, via an animal experiment. Physical and chemical analyses indicated that a relatively stable liposome with a uniform nano-size, which was formed, possessed good transdermal permeability that was 2.74 folds higher than that of the free peptide (F). LLRF exhibited a higher transdermal permeation performance that was of 3.65 folds higher than that of the free one, which was substantiated via confocal laser scanning fluorescence microscopy. The mouse UVB photoaging model trial confirmed that the LLRF technology exerted a significant synergistic effect compared to liposome technology, or free peptide, by downregulating inflammatory factors (IL-6, TNF-α), inhibiting the mRNA and protein expression of matrix metalloproteinases (MMP1, MMP3), promoting the mRNA and protein expression of related collagens (Procollagen, Col1α1 and Col3α1), and repairing the stratum corneum barrier function, as evidenced by trans-epidermal water loss (TEWL), skin cuticle hydration (SCH), and decreased expression of β-gal, an aging marker. These findings indicated that photoaging skin can be effectively and comprehensively rejuvenated, and that even photodamage can be reversed, thereby restoring the original physiological characteristics of healthy skin. Clinical tests have confirmed that although liposome technology is an effective antiaging method which helps exert tightening and anti-wrinkle effects on human skin, LLRF is an even more effective anti-aging technique. This study reveals a highly effective technique involving a combination physical and chemical therapy that may be utilized for antiaging purposes as well as repairing lightly damaged skin, and can be made readily available in the future.

Preparation and characterization of niosomes for the delivery of a lipophilic model drug: comparative stability study with liposomes against phospholipase-A2

Vesicular nanocarriers like niosomes and liposomes are widely researched for controlled drug delivery systems, with niosomes emerging as promising alternatives due to their higher stability and ease of manufacturing. This study aimed to develop and characterize a niosomal formulation for the encapsulation and sustained release of temozolomide (TMZ), a model lipophilic drug, and to compare the stability of niosomes and liposomes, with a particular focus on the behavior of their lipid bilayers. Niosomes were prepared using the thin-film hydration method, composed of Span 60 (Sorbitan monostearate), cholesterol, and soy lecithin in varying molar ratios. The study investigated critical properties such as drug loading capacity, release kinetics, and resistance to enzymatic degradation. The optimized formulation was analyzed for drug entrapment efficiency and stability against phospholipase A2 (PLA2) degradation. The optimized niosomal formulation, with a 4:2:1 molar ratio of Span 60: cholesterol, achieved a high TMZ entrapment efficiency of 73.23 ± 1.02% and demonstrated sustained drug release over 24 hours. In comparison, liposomes released their TMZ payload within 4 hours upon exposure to PLA2, while the niosomes maintained their release profile, indicating superior stability. Spectroscopic and thermal analysis confirmed successful drug encapsulation with no component incompatibilities.

A Modified Self-micro Emulsifying Liposome for Bioavailability Enhancement of Quercetin and its biological effects

Quercetin (QT) is a chief dietary flavonoid with a myriad of health benefits, however, its poor solubility and low bioavailability restrict its food application. Thus, the present study aimed at enhancing its solubility using a modified self-micro emulsifying system (QT-TPGS-QS). The stability of liposome was assessed via monitoring of its particle indexes (size, zeta potential, PDI, stability towards in-vitro digestion, drug release, and encapsulation efficiency). Further, antibacterial and cellular antioxidant potential of liposomes were determined. QT-TPGS-QS exhibited good optical clarity with a loading ratio of 2.1%. The liposome showed uniform spherical and regular shape (< 100 nm) with a QT release rate of 85.61% ± 0.32% in simulated in-vitro digestion. QT-TPGS-QS demonstrated superior antibacterial activity compared to QT alone against Escherichia coli, Staphylococcus aureus, and Salmonella. In-vitro antioxidant evaluation confirmed that the QT-TPGS-QS exhibited a significantly higher free radical scavenging ability than QT alone. Cellular assay confirmed that QT-TPGS-QS (15 μg/mL) exhibited a good protection effect on oxidative stress induced by H2O2. Catalase (CAT) and glutathione peroxidase (GSH-Px) levels were significantly upregulated, concurrent with a reduction of malondialdehyde (MDA) suggesting that QT-TPGS-QS might be effective in inhibiting the production of intracellular reactive oxygen species (ROS), and to be considered as food additive or in nutraceuticals.

Effect of chitosan coating on the characterization and stability of the CPH liposomes

Effect of chitosan coating on the characterization and stability of the CPH liposomes

Enhancement of oral bioavailability of ibrutinib using a liposil nanohybrid delivery system.

Liposils, synthesized via the liposome templating method, offer a promising strategy for enhancing liposome stability by employing a silica coating. This study focuses on the development of nanocarriers utilizing silica-coated nanoliposomes for encapsulating the poorly water-soluble drug, ibrutinib. Ibrutinib-loaded nanoliposomes were meticulously formulated using the reverse-phase evaporation technique, serving as templates for silica coating, resulting in spherical liposils with an average size of approximately 240 nanometers. Comprehensive characterization of the liposil's physical and chemical properties was conducted using various analytical methods, including dynamic light scattering, transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis. Liposils demonstrated superior performance compared to ibrutinib-loaded nanoliposomes, showing sustained drug release profiles in simulated intestinal fluids and resistance to simulated gastric fluid, as confirmed by dissolution studies. Moreover, ibrutinib liposils exhibited a significant increase in half-life (4.08-fold) and notable improvement in bioavailability (3.12-fold) compared to ibrutinib suspensions, as determined by pharmacokinetic studies in rats. These findings underscore the potential of liposils as nanocarriers for orally delivering poorly water-soluble drugs, offering enhanced stability and controlled release profiles, thereby improving bioavailability prospects and therapeutic efficacy. This approach holds promise for addressing challenges associated with the oral administration of drugs with limited solubility, thereby advancing drug delivery technologies and clinical outcomes in pharmaceutical research and development.

Thermosensitive Liposomes for Gemcitabine Delivery to Pancreatic Ductal Adenocarcinoma.

Treatment of pancreatic ductal adenocarcinoma with gemcitabine is limited by an increased desmoplasia, poor vascularization, and short plasma half-life. Heat-sensitive liposomes modified by polyethylene glycol (PEG; PEGylated liposomes) can increase plasma stability, reduce clearance, and decrease side effects. Nevertheless, translation of heat-sensitive liposomes to the clinic has been hindered by the low loading efficiency of gemcitabine and by the difficulty of inducing hyperthermia in vivo. This study was designed to investigate the effect of phospholipid content on the stability of liposomes at 37 °C and their release under hyperthermia conditions; this was accomplished by employing a two-stage heating approach. First the liposomes were heated at a fast rate, then they were transferred to a holding bath. Thermosensitive liposomes formulated with DPPC: DSPC: PEG2k (80:15:5, mole%) exhibited minimal release of carboxyfluorescein at 37 °C over 30 min, indicating stability under physiological conditions. However, upon exposure to hyperthermic conditions (43 °C and 45 °C), these liposomes demonstrated a rapid and significant release of their encapsulated content. The encapsulation efficiency for gemcitabine was calculated at 16.9%. Additionally, fluorescent analysis during the removal of unencapsulated gemcitabine revealed an increase in pH. In vitro tests with BxPC3 and KPC cell models showed that these thermosensitive liposomes induced a heat-dependent cytotoxic effect comparable to free gemcitabine at temperatures above 41 °C. This study highlights the effectiveness of the heating mechanism and cell models in understanding the current challenges in developing gemcitabine-loaded heat-sensitive liposomes.

Preparation, Pharmacokinetics and Anti-Liver Injury Pharmacodynamic Study of Esculin Loaded Liposomes Modified by TPGS

In this study, Esculin (ES)-loaded liposomes modified with TPGS (ES-TPGS-Ls) were successfully prepared to enhance bioavailability and hepatoprotective activity of this coumarin glucoside. We utilize thin-film dispersion to fabricate ES-TPGS-Ls. The size, polydispersed index (PDI), Zeta potential (Z-potential), morphology, and encapsulation effectiveness of the liposomes were all evaluated afterwards. The storage stability of ES-TPGS-Ls at 4 °C was investigated. The findings showed that ES-TPGS-Ls had spherical nanoparticles with 194.47±8.54 nm as the mean size, 0.239±0.011 as PDI, and −21.16±0.97) mV as Z-potential coupled with encapsulation efficiency (EE) of 91.85±0.44%. Storage stability of liposomes at 4 °C was maintained within one week. Pharmacokinetic study showed that the relative oral bioavailability of ES-TPGS-Ls increased by 2.38 times. Pharmacodynamic studies showed that the developed liposomes could enhance the hepatoprotective activity of ES. Overall, the ES-TPGS-Ls significantly enhanced the bioavailability of esculin, thereby enhancing the in vivo hepatoprotective effect of ES.

Strategic Developments in Polymer-Functionalized Liposomes for Targeted Colon Cancer Therapy: An Updated Review of Clinical Trial Data and Future Horizons.

Liposomes, made up of phospholipid bilayers, are efficient nanocarriers for drug delivery because they can encapsulate both hydrophilic and lipophilic drugs. Conventional cancer treatments sometimes involve considerable toxicities and adverse drug reactions (ADRs), which limits their clinical value. Despite liposomes' promise in addressing these concerns, clinical trials have revealed significant limitations, including stability, targeted distribution, and scaling challenges. Recent clinical trials have focused on enhancing liposome formulations to increase therapeutic efficacy while minimizing negative effects. Notably, the approval of liposomal medications like Doxil demonstrates their potential in cancer treatment. However, the intricacy of liposome preparation and the requirement for comprehensive regulatory approval remain substantial impediments. Current clinical trial updates show continued efforts to improve liposome stability, targeting mechanisms, and payload capacity in order to address these issues. The future of liposomal drug delivery in cancer therapy depends on addressing these challenges in order to provide patients with more effective and safer treatment alternatives.

Quantitative determination of liposomal irinotecan and SN-38 concentrations in plasma samples from children with solid tumors: Use of a cryoprotectant solution to enhance liposome stability

Preclinical studies have demonstrated that liposomal irinotecan (CPT-11), a topoisomerase I inhibitor, has broad activity against adult cancers, including pancreatic, gastric, colon, lung, glioma, ovarian, and breast cancer. Encapsulation of irinotecan into liposomes can modify its pharmacokinetic properties dramatically. Also, the pharmacokinetic profiles of liposomal drug formulations are not fully understood; thus, bioanalytical methods are needed to separate and quantify nonencapsulated vs. encapsulated concentrations. In this study, two robust, specific, and sensitive LC-MS/MS methods were developed and validated to separate and quantify the nonencapsulated CPT-11 (NE-CPT-11) from the sum-total CPT-11 (T-CPT-11) and its major metabolite, SN-38, in human plasma after intravenous administration of liposomal irinotecan. NE-CPT-11 and SN-38 were separated from plasma samples by using solid-phase extraction, and T-CPT-11 was measured by protein precipitation. The liposomal CPT-11 formulation was unstable during sample storage and handling, resulting in elevated NE-CPT-11 concentration. To improve the stability of liposomal CPT-11, a cryoprotectant solution was added to human plasma samples prior to storage and processing. CPT-11, SN-38, and their respective internal standards, CPT-11-d10 and SN-38-d3, were chromatographically separated on a reversed-phase C18 analytical column. The drugs were detected on a triple quadrupole mass spectrometer in the positive MRM ion mode by monitoring the transitions 587.3 > 124.1 (CPT-11) and 393.0 > 349.1 (SN-38). The calibration curves demonstrated a good fit across the concentration ranges of 10–5000 ng/mL for T-CPT-11, 2.5–250 ng/mL for NE-CPT-11, and 1–500 ng/mL for SN-38. The accuracy and precision were within the acceptable limits, matrix effects were nonsignificant, recoveries were consistent and reproducible, and the analytes were stable under all tested storage conditions. Finally, the LC-MS/MS methods were successfully applied in a phase I clinical pharmacokinetic study of nanoliposomal irinotecan (Onivyde®) in pediatric patients with recurrent solid malignancies or Ewing sarcoma.

Electrochemical Investigation of the Stability of Poly-Phosphocholinated Liposomes.

Poly[2-(methacryloyloxy)ethyl phosphorylcholine] liposomes (pMPC liposomes) gained attention during the last few years because of their potential use in treating osteoarthritis. pMPC liposomes that serve as boundary lubricants are intended to restore the natural lubrication properties of articular cartilage. For this purpose, it is important that the liposomes remain intact and do not fuse and spread as a lipid film on the cartilage surface. Here, we investigate the stability of the liposomes and their interaction with two types of solid surfaces, gold and carbon, by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). With the aid of a hydrophilic species used as an electroactive probe in the solution, the charge transfer characteristics of the electrode surfaces are obtained. Additionally, from EIS, the capacitance characteristics of the surfaces are derived. No decrease of the peak currents and no displacement of the peak potentials to greater overpotentials are observed in the CV experiments. No decrease in the apparent capacitance and increase in the charge transfer resistance is observed in the EIS experiments. On the contrary, all parameters in both CV and EIS do change in the opposite direction. The obtained results confirm that there is only physical adsorption without fusion and spreading of the pMPC liposomes and without the formation of lipid films on the surfaces of both gold and carbon electrodes.

Molecular Dynamics Simulations Reveal Octanoylated Hyaluronic Acid Enhances Liposome Stability, Stealth and Targeting.

Liposome-based drug delivery systems have been widely used in drug and gene delivery. However, issues such as instability, immune clearance, and poor targeting have significantly limited their clinical utility. Consequently, there is an urgent need for innovative strategies to improve liposome performance. In this study, we explore the interaction mechanisms of hyaluronic acid (HA), a linear anionic polysaccharide composed of repeating disaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine connected by alternating β-1,3 and β-1,4 glycosidic linkages, and its octanoylated derivates (OHA) with liposomes using extensive coarse-grained molecular dynamics simulations. The octyl moieties of OHA spontaneously inserted into the phospholipid bilayer of liposomes, leading to their effective coating onto the surface of liposome and enhancing their structural stability. Furthermore, encapsulating liposome with OHA neutralized their surface potential, interfering with the formation of a protein corona known to contribute to liposomal immune clearance. Importantly, the encapsulated OHA maintained its selectivity and therefore targeting ability for CD44, which is often overexpressed in tumor cells. These molecular-scale findings shed light on the interaction mechanisms between HA and liposomes and will be useful for the development of next-generation liposome-based drug delivery systems.

Stabilization of cationic liposomes using hyaluronic acid-modified gold nanoparticles by post-microfluidics conjugation approach for drug delivery applications

lipid-based nanoparticles (LNPs), particularly liposomes, have gained prominence throughout the pharmaceutical sector as a hopeful means for transporting a range of therapeutic agents. Improving LNPs stability is crucial in pharmaceuticals, and drug delivery systems to ensure their effectiveness and reliability. The current research was undertaken to design a pH-responsive hyaluronic acid-modified gold nanoparticle-stabilized cationic liposome (SPC/DOPE/DOTAP) system (HA-SH/AuNPs@liposomes) to improve the stability of liposomes. This was achieved through a post-microfluidics conjugation technique to encapsulate the 5-fluorouracil (5-FU) anticancer drug, usually employed in nonmelanoma skin cancer (NMSC) treatment. Microfluidics is an emerging technology that can be employed as a powerful tool for designing nanoscale liposomes with highly uniform size distributions and acceptable colloidal stability. Utilizing a microfluidics toroidal mixer, affixed HA-SH/AuNPs (size: 12.56 ± 1.65 nm) to positively charged liposomes (size: 75 ± 0.68 nm and PDI: 0.032 ± 0.0021). These liposomes exhibited strong stability, limited fusion propensity, and minimal cargo release at neutral pH. The gold stabilizers detached in an acidic environment, releasing encapsulated therapeutic agents. The dynamic light scattering (DLS) analysis results indicate that HA-SH/AuNPs@Liposomes (size: 102.2 ± 1.3 nm and PDI: 0.11 ± 0.01) exhibit greater stability than bare liposomes over 4 weeks at 4 °C. This enhanced stability can be attributed to the presence of HA-SH/AuNPs in the liposomal structure. This research outlines a systematic method to optimize the size rapidly and PDI of liposomes by employing the Design of Experiments (DoE). The results highlighted that utilizing both the microfluidic technique and gold nanoparticle-stabilized liposomes offers benefits for creating controlled drug release formulations. This approach leads to enhanced biopharmaceutical characteristics and improved scalability of liposomal formulations.

Enhancing the stability and bio-accessibility of carotenoids extracted from canistel (Lucuma nervosa) via liposomes encapsulation

Canistel (Lucuma nervosa) is a valuable natural source of carotenoids, but their use in the food industry is hampered by low extraction efficiency, poor stability, and limited bio-accessibility. HPLC results showed that a deep eutectic solvent (DES) composed of D-menthol and canoic acid (Men-CaA) has significantly higher extraction yields for lycopene (498.66 ± 3.20 μg/mL DW) and β-carotene (6.43 ± 0.23 μg/mL DW) than corn oil. UV-VIS spectrophotometry combined with response surface methodology results confirmed that the best encapsulation efficiency of liposome for lycopene and β-carotene was attained in the temperature range of 30–70 °C, with the ratio of carotenoid extract to liposome of 1:25 (w/w), the ratio of phospholipids to cholesterol, and the ratio of aqueous phase to lipid phase of 2:1 (v/v). SEM analysis revealed that liposome-encapsulated carotenoid extract formed spherical structures with a uniform texture and rough surface. The ζ-potential assay confirmed the highest stability of liposomes at pH 7. FTIR spectroscopy indicated effective encapsulation of canistel-derived carotenoids by liposomes. Furthermore, liposomes encapsulation improved the thermal and storage stability and bio-accessibility of lycopene and β-carotene. Encapsulating canistel carotenoids in liposomes significantly enhances their stability and bio-accessibility, presenting a viable strategy for preserving the efficacy of food-based active ingredients.

Preparation of a novel ATP liposome and its regulation of postharvest senescence in Agaricus bisporus

This study aimed to prepare an adenosine triphosphate (ATP) liposome by reverse evaporation to improve the stability of exogenous ATP and regulate its sustained release. Its microstructure and physicochemical indexes were systematically characterized to obtain the optimal drug–lipid ratio. The results showed that egg yolk lecithin (EYL)/ATP-5 exhibited minimal vesicle size with good encapsulation efficiency (63.26 % ± 0.20 %). The storage stability and thermogravimetric (TG) results showed that EYL/ATP-5 exhibited better dispersion properties during storage; however, it did not significantly affect the thermal stability of liposomes. Transmission electron microscopy results further corroborated that the liposomes at this ratio exhibited a homogeneous and unaggregated vesicular structure, which was favorable for the maintenance of liposome stability. EYL/ATP-5 treatment was used for the postharvest preservation of white mushrooms. The results showed that EYL/ATP-5 treatment maintained the firmness of white mushroom substrate after harvesting, delayed browning, inhibited its respiration, and postponed the quality deterioration of white mushrooms. In conclusion, the ATP liposomes obtained in this study provided a new idea for storing and preserving harvested edible fungi.

Alginate nanogel-embedded liposomal drug carriers facilitate drug delivery efficiency in arthritis treatment

Despite numerous advantages of liposomes in treating rheumatoid arthritis (RA), the in vivo stability remains a critical issue. Current strategies for improving liposomal stability often compromise their original properties. Herein, we designed an alginate nanogel-embedded liposome aiming at retaining those inherent advantages while enhancing their in vivo stability. The introduction of alginate network within the liposome core can provide mechanical support and controlled drug release without affecting the surface properties. Results showed the cross-linking of alginate network within the inner core of liposomes elevated the particle rigidity to 3 times, allowing for improved stability and decreased drug leakage. Moreover, this nanogel-embedded liposome with optimized elasticity obviously facilitated cellular uptake in inflammatory macrophages. When entering blood circulation, increased rigidity altered the composition of protein corona on the particle surface, resulting in 2-fold increase in circulation time and improved drug accumulation in arthritic joints. When anti-inflammatory chlorogenic acid (CA) was encapsulated into the nanogel network, this CA-loaded nanogel-embedded liposome significantly inhibited ROS production and inflammatory response, ultimately achieved superior therapeutic outcome in arthritic rats. Results demonstrated that this nanogel-embedded liposomes can essentially retain the inherent advantages and overcome the drawbacks of liposomes, thereby improving the drug delivery efficiency.

Calcein release from DPPC liposomes by phospholipase A2 activity: Effect of cholesterol and amphipathic copolymers

In this study, we evaluated the impact of incorporating diblock and triblock amphiphilic copolymers, as well as cholesterol into DPPC liposomes on the release of a model molecule, calcein, mediated by exogenous phospholipase A2 activity. Our findings show that calcein release slows down in the presence of copolymers at low concentration, while at high concentration, the calcein release profile resembles that of the DPPC control. Additionally, calcein release mediated by exogenous PLA2 decreases as the amount of solubilized cholesterol increases, with a maximum between 18 mol% and 20 mol%. At concentrations higher than 24 mol%, no calcein release was observed. Studies conducted on HEK-293 and HeLa cells revealed that DPPC liposomes reduced viability by only 5% and 12%, respectively, after 3 hours of incubation, while DPPC liposome in presence of 33 mol% of Cholesterol reduced viability by approximately 11% and 23%, respectively, during the same incubation period. For formulations containing copolymers at low and high concentrations, cell viability decreased by approximately 20% and 40%, respectively, after 3 hours of incubation. Based on these preliminary results, we can conclude that the presence of amphiphilic copolymers at low concentration can be used in the design of new DPPC liposomes, and together with cholesterol, they can modulate liposome stabilization. The new formulations showed low cytotoxicity in HEK-293 cells, and it was observed that calcein release depended entirely on PLA2 activity and the presence of calcium ions.

Controlling the formation of ionic complex vesicles through double-tailed surfactants.

Liposomes are often used in cosmetics since they are naturally derived and have excellent texture enhancing capabilities. However, when preparing them by using phospholipids with unsaturated acyl groups, they easily suffer from oxidative degradation. Accordingly, hydrogenated phospholipids are preferred, however, it is difficult to prepare stable liposomes due to its high gel-liquid crystalline phase transition temperature. On the other hand, although dialkyl dimethyl ammonium type cationic surfactants are widely known to form vesicles, they have rarely been used for skincare products except for water-in-oil type emulsion creams stabilized by organically modified clay minerals. We decided to overcome all of the problems above through ionic complex vesicles formed by double-tailed cationic and anionic surfactants. Distearyl dimethyl ammonium chloride (DSAC) and sodium dilauramidoglutamide lysine (DLGL) were selected as cationic and anionic surfactants, respectively. Differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SWAXS) measurements were performed to confirm the DSAC/DLGL/water ternary phase diagram. Newly developed ionic complex vesicle formation was confirmed by cryogenic transmission electron microscopy (cryo-TEM). The adsorbed cosmetic film structure on the skin invivo was evaluated through the polarized infrared external reflection (PIR-ER). Finally, a cosmetic lotion formula was developed and the vesicle size was determined by dynamic light scattering (DLS). DSC and SWAXS data indicated that stable vesicles could be obtained at a molar ratio of DLGL to DSAC = 6:4. At this molar ratio, multi lamellar vesicles with diameters less than 100 nm were observed through cryo-TEM. PIR-ER data revealed that the developed vesicles formed a highly perpendicular orientation to the human skin surface. We have succeeded in formulating a cosmetic lotion containing developed vesicles with a mean diameter of 63.2 nm, which was stable over 1 month at 0, 37, and 50°C. Our newly developed vesicles can be easily obtained through a coagulation process. Also, the adsorbed film structure supported by PIR-ER experiments implies that the developed lotion has an excellent texture that is the same as cosmetic lotions containing liposomes. Therefore, it's possible that this ionic complex vesicle could take the place of liposomes.

Manufacturing process of liposomal Formation: A coarse-grained molecular dynamics simulation

A method of producing liposomes has been previously developed using a continuous manufacturing technology that involves a co-axial turbulent jet in co-flow. In this study, coarse-grained molecular dynamics (CG-MD) simulations were used to gain a deeper understanding of how the self-assembly process of liposomes is affected by the material attributes (such as the concentration of ethanol) and the process parameters (such as temperature), while also providing detailed information on a nano-scale molecular level. Specifically, the CG-MD simulations yield a comprehensive internal view of the structure and formation mechanisms of liposomes containing DPPC, DPPG, and cholesterol molecules. The importance of this work is that structural details on the molecular level are proposed, and such detail is not possible to obtain through experimental studies alone. The assessment of structural properties, including the area per lipid, diffusion coefficient, and order parameters, indicated that a thicker bilayer was observed at higher ethanol concentrations, while a thinner bilayer was present at higher temperatures. These conditions led to more water penetrating the interior of the bilayer and an unstable structure, as indicated by a larger contact area between lipids and water, and a higher coefficient of lipid lateral diffusion. However, stable liposomes were found through these evaluations at lower ethanol concentrations and/or lower process temperatures. Furthermore, the CG-MD model was further compared and validated with experimental and computational data including liposomal bilayer thickness and area per lipid measurements.