Properties Of Liposomes Research Articles

The manufacturing of 3D-printed microfluidic chips to analyse the effect upon particle size during the synthesis of lipid nanoparticles.

The process of 3D printing to produce microfluidic chips is becoming commonplace, due to its quality, versatility and newfound availability. In this study, a UV liquid crystal display (LCD) printer has been implemented to produce a progression of microfluidic chips for the purpose of liposomal synthesis. The emphasis of this research is to test the limitations of UV LCD printing in terms of resolution and print speed optimisation for the production of microfluidic chips. By varying individual channel parameters such as channel length and internal geometries, the essential channel properties for optimal liposomal formulation are being investigated to act as a basis for future experimentation including the encapsulation of active pharmaceutical ingredients. Using the uniquely designed chips, liposomes of ≈120 nm, with polydispersity index values of ≤0.12 are able to be reproducibly synthesised. The influence of total flow rates and lipid choice is investigated in depth, to provide further clarification on how a microfluidic setup should be optimised. In-depth explanations of the importance of each channel parameter are also explained throughout, with reference to their importance for the properties of a successful liposome.

Lipid-A-dependent and cholesterol-dependent dynamics properties of liposomes from gram-negative bacteria in ESKAPE

AntiMicrobial Resistance (AMR) is a worldwide health emergency. ESKAPE pathogens include the most relevant AMR bacterial families. In particular, Gram-negative bacteria stand out due to their cell envelope complexity which exhibits strong resistance to antimicrobials. A key element for AMR is the chemical structure of lipid A, modulating the physico-chemical properties of the membrane and permeability to antibiotics. Liposomes are used as models of bacterial membrane infective vesicles. In this work, coarse-grained molecular dynamics simulations were used to model liposomes from ESKAPE Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa). We captured the role of lipid A, cardiolipin and cholesterol on liposome morphology and physico-chemical properties. Additionally, the reported antimicrobial peptides Cecropin B1, JB95, and PTCDA1-kf, were used to unveil their implications on membrane disruption. This study opens a promising starting point to understand molecular keys of bacterial membranes and to promote the discovery of new antimicrobials to overcome AMR.

Structure and interaction roles in the release profile of chalcone-loaded liposomes

The structures and molecular interactions of established synthetic chalcones were correlated with their release profiles from asolectin liposomes. The effects of chalcones on the properties of liposomes were evaluated by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-VIS), horizontal attenuated total reflection Fourier transform infrared (HATR-FTIR), 31P nuclear magnetic resonance (31P NMR), zeta (ζ) potential and differential scanning calorimetry (DSC). The profiles and mechanisms of release were accessed according to the Korsmeyer-Peppas model. Results obtained allowed the establishment of a relationship between the chalcone release profile and 1) the ordering effects of chalcones in different membrane regions, 2) their polar or interfacial location in the lipid layer, 3) the influence of hydroxy and methoxy substituents, 4) their effect on reorientation of lipid choline-phosphate regions. The obtained data may improve the development of chalcone-based systems to be used in the therapy of chronic and acute diseases.

Effect of polyol type on the structure and properties of lecithin liposomes prepared using the polyol dilution method

The polyol dilution (PD) method is an approach for preparing liposomes by pre-mixing a lipid/polyol binary mixture, followed by hydration, and is widely used in the cosmetics industry. In this method, polyols play an important role in the formulation design and application, however, the effect of the polyol type on liposomes (PD-liposomes) is yet to be understood. In this study, we investigated the effect of three types of polyols—glycerol (Gly), propylene glycol (PG), and 1,3-butylene glycol (BG)—on the physicochemical properties of PD-liposomes composed of hydrogenated egg yolk lecithin (EL). The particle size of PD-liposomes was controlled by adjusting the type and concentration of the polyols. Furthermore, the addition of polyols improved the dispersion stability, indicating that PD-liposomes are suitable for industrial applications. The morphology of lipid/polyol binary mixture was the determining factor of the liposome structure, and the formation region of unilamellar vesicles (ULVs) and multilamellar vesicles (MLVs) was closely related to the dielectric constant of the dispersion medium. ULVs were formed using a high dielectric constant dispersion medium, such as Gly, and MLVs were formed using a low dielectric constant dispersion medium, such as PG and BG at high concentrations. This study showed that the addition of polyols improves the phase homogeneity of the bilayer and that PG or BG is more effective than Gly. The control of the homogeneity of the bilayer phase is an effective technique to prevent leakage and control the sustained release of the active ingredient; thus, this method enhances the efficacy of the active ingredient. This study is the first to systematically elucidate the control mechanisms of the physicochemical properties of PD-liposomes, including the particle size, dispersion stability, shape, and phase state of the bilayer. Our findings will contribute to the wide range of applications of PD-liposomes.

Preparation of Magnetized Mesenchymal Stem Cells Using Magnetic Liposomes to Enhance Their Retention in Targeted Tissue -Evaluation of Retention and Anti-inflammatory Efficiency in Skeletal Muscle

Magnetic nanoparticle-incorporated liposomes (magnetic liposomes) are considered a promising site-specific drug delivery carrier. Although there are many reports on the development of magnetic liposomes, most of them focus on the characteristics of magnetic nanoparticles, rather than liposomes. Therefore, we first evaluated the effect of the physicochemical properties of magnetic liposomes on their interaction with cells. The highest cellular uptake and retention under a magnetic field was observed using small magnetic cationic liposomes. However, magnetic cationic liposomes exhibited strong cytotoxicity. Based on these results, we constructed complexes of less toxic magnetic anionic liposomes (Mag-AL) and atelocollagen (ATCOL), a biocompatible cationic biomaterial. The cellular associated amount of Mag-AL under a magnetic field was significantly increased when Mag-AL was complexed with ATCOL, and it was comparable to that of magnetic cationic liposomes. Additionally, Mag-AL/ATCOL complexes produced no cytotoxic effect. Moreover, liver accumulation of Mag-AL/ATCOL complexes was significantly increased at a magnetic field-exposed region after intravenous injection in rats. These results indicate that Mag-AL/ATCOL complexes may be a safe and efficient magnetic responsive drug carrier. Next, we applied Mag-AL/ATCOL complexes to prepare magnetized cells for effective cell therapy. Mesenchymal stem cells (MSCs), which have the capacity to suppress tissue inflammation, were efficiently magnetized by incubation with Mag-AL/ATCOL complexes under a magnetic field. Intramuscularly injected magnetized MSCs were significantly retained in mouse skeletal muscle in the presence of a magnetic field and modulated tissue inflammatory responses. These results suggest that magnetized MSCs are useful for muscle regeneration.

PASylation improves pharmacokinetic of liposomes and attenuates anti-PEG IgM production: An alternative to PEGylation

PASylation, which was recently reported as the conjugation of pharmacologically active compounds with polypeptide sequences mainly made of proline, alanine and serine, has been proposed as an alternative to PEGylation. In this study, we designed PAS-modified liposomes (PASylated liposomes) and studied the effect of the incorporation of PAS-lipid on the stability and pharmacokinetic properties of liposomes, and compared them both in vitro and in vivo to PEGylated liposomes. Results showed that PASylated liposomes modified with single-chained PAS-lipid C16-(PA3)7 (SC-PAS-Lip) showed comparable storage and serum stability to PEGylated liposomes (PEG-Lip), and a significantly decreased macrophage uptake compared with unmodified liposomes. SC-PAS-Lip displayed long circulating pharmacokinetic profile which was not impacted by the repeated administration of liposomes, and they were less likely to induce the production of anti-PEG IgM compared with PEGylated liposomes, presenting PASylation as an alternative liposome modification strategy to PEGylation.

A Review on the Delivery of Plant-Based Antidiabetic Agents Using Nanocarriers: Current Status and Their Role in Combatting Hyperglycaemia.

Diabetes mellitus is a prevalent metabolic syndrome that is associated with high blood glucose levels. The number of diabetic patients is increasing every year and the total number of cases is expected to reach more than 600 million worldwide by 2045. Modern antidiabetic drugs alleviate hyperglycaemia and complications that are caused by high blood glucose levels. However, due to the side effects of these drugs, plant extracts and bioactive compounds with antidiabetic properties have been gaining attention as alternative treatments for diabetes. Natural products are biocompatible, cheaper and expected to cause fewer side effects than the current antidiabetic drugs. In this review, various nanocarrier systems are discussed, such as liposomes, niosomes, polymeric nanoparticles, nanoemulsions, solid lipid nanoparticles and metallic nanoparticles. These systems have been applied to overcome the limitations of the current drugs and simultaneously improve the efficacy of plant-based antidiabetic drugs. The main challenges in the formulation of plant-based nanocarriers are the loading capacity of the plant extracts and the stability of the carriers. A brief review of lipid nanocarriers and the amphipathic properties of phospholipids and liposomes that encapsulate hydrophilic, hydrophobic and amphiphilic drugs is also described. A special emphasis is placed on metallic nanoparticles, with their advantages and associated complications being reported to highlight their effectiveness for treating hyperglycaemia. The present review could be an interesting paper for researchers who are working in the field of using plant extract-loaded nanoparticles as antidiabetic therapies.

Enhancement of the Transdermal Delivery of Nonsteroidal Anti-inflammatory Drugs Using Liposomes Containing Cationic Surfactants

New hybrid liposomes based on cationic amphiphiles with different structures of the head group (cetyltrimethylammonium bromide (CTAB), 3-hexadecyl-1-hydroxyethylimidazolium bromide (IA-16(OH)), 1-(butylcarbamoyl)oxyethyl-3-hexadecylimidazolium bromide (IAC 16(Bu)), and hexadecylmethylpyrrolidinium bromide (PR-16)) were developed for transdermal administration of nonsteroidal anti-inflammatory drugs. The different surfactant/lipid compositions were studied to obtain stable liposomes with high functionality. The hydrodynamic diameter of cationic liposomes was ∼110 nm. An admixture of cationic surfactants and PC liposomes improves the physicochemical properties of vesicles and transdermal diffusion rate and prolongs the release of drugs. Liposomal diclofenac sodium (DS) and ketoprofen (KP) were tested (using Franz cells) for transdermal penetration. Drug diffusion monitoring for 48 h demonstrated that the maximum DS and KP penetration through the synthetic membranes (Strat-M) is characterized by values of 255 ± 2 and 186 ± 3 μg/cm2, respectively. The influence of the surfactant head group on the properties (stability, release profile, permeability) of cationic liposomes was shown for the first time. While the drug specificity is evident for the rate of release, the permeability increases as follows: conventional liposomes < CTAB/PC < PR-16/PC < IAC-16(Bu)/PC < IA-16(OH)/PC for both medicines. The rat paw edema model was used to assess the anti-inflammatory effect of the IA-16(OH)/PC leader formulation in vivo. It was found that liposomal DS and KP are effective for relieving rat paw edema. It should be noted that DS-loaded hybrid liposomes demonstrated the highest therapeutic efficacy compared to conventional vesicles.

The effect of selected bisphenols on model erythrocyte membranes of different cholesterol content

Bisphenols belong to the group of environmental pollutants with proven harmful impact on human red blood cells. However, the exact effect of these substances may vary depending on the lipid composition of the cell membrane, since this structure is the first barrier between the cell interior and the external environment. The aim of this work was to analyze the influence of bisphenol A (BPA), bisphenol S (BPS) and their 1:1 mixture on model human erythrocyte membranes, composed of sphingomyelin (SM), phospatidylcholine (PC) and cholesterol (Chol). Due to the postulated correlation between the content of cholesterol in biomembranes and the toxic effect of bisphenols the model systems of different sterol concentrations (10, 20 and 40 mol% of Chol) were used in the studies. In the experiments, Langmuir monolayer technique accompanied with Brewster Angle Microscopy were applied and liposome properties were investigated. The obtained findings reveal that, in the investigated range of the sterol content, the effect of BPA, namely the changes of the organization and stability of model membranes and weakening of the attractive lipid-lipid interactions, is strongly dependent on the concentration of Chol in the system. The higher the sterol content, the stronger the BPA-induced alterations in membrane properties. However taking into account the results reported previously for the system containing 33.3% of cholesterol, it seems that the relationship between the effect of BPA and the amount of Chol is not linear for higher sterol concentrations. In contrast, BPS shows a much weaker influence on model erythrocyte membranes and does not act selectively on the systems studied. The effect of a mixture of BPA and BPS is intermediate between that of BPA and BPS used separately, however, the observed effects appear to be determined only by the presence of BPA in the system. Thus, the concentration of cholesterol in human erythrocyte membranes, which depends on factors such as age or health status, may play a key role in the toxic effects of BPA but not BPS.

Production and stability of food-grade liposomes containing microbial carotenoids from Rhodotorula mucilaginosa

We demonstrated the technical feasibility of obtaining carotenoids-loaded liposomes from soybean lecithins using an ethanol injection technique. We evaluated the influence of three lecithin-types with different phosphatidylcholine content and microbial carotenoids produced by yeast Rhodotorula mucilaginosa on liposome properties. The liposomal systems were characterized by average hydrodynamic diameter, polydispersity index, ζ-potential, and stability under different pH and heat temperature conditions commonly observed in food processing. The lecithin type and concentration used to produce liposomes significantly influence the hydrodynamic diameter, polydispersity index, and ζ-potential. In general, we observed the presence of liposomes with diameters ranging from 150 to 221 nm and a polydispersity index of approximately 0.300 when Lipoid S45 was used. The incorporation of microbial carotenoids promoted a significant increase in hydrodynamic diameter and ζ-potential, while carotenoid-loaded liposomes showed a lower polydispersity index. The carotenoid-loaded liposomes submitted to pH 3 presented a visual phase separation, while liposomes submitted at 70 °C for 15 min showed degradation of carotenoids equal to control assay (without treatment). We concluded that it is possible to incorporate microbial carotenoids in food-grade liposomal systems, allowing for further studies aimed at their application as an encapsulating and/or delivery system to be used in aqueous food products.

Characterization of lecithin liposomes prepared by polyol dilution method using 1,3-butylene glycol

Liposomes, which are formed from phospholipids, have been widely applied in cosmetics for skin enhancement. The polyol dilution (PD) method is commonly used to prepare liposomes in the cosmetic industry. An understanding of liposome physicochemical properties is essential for cosmetic-formulation design and application. However, there have been few studies on the characterization of liposomes prepared by the PD method (PD-liposomes). Here, we studied the effect of 1,3-butylene glycol (BG) on the formation of egg-yolk lecithin (EL)-based PD-liposomes. Furthermore, the use of BG to control the liposome structural and membrane properties was investigated. The use of BG enables particle-size control of liposomes and improves the dispersion stability. In the preparation of PD-liposomes, the structure of the molecular assembly in the EL/BG binary system prior to hydration is an important factor in determining the type of PD-liposome produced. The key step in the preparation of unilamellar and multilamellar vesicles is the formation of spherical vesicles with low BG concentrations, or a stacked planar lamellar structure with high BG concentrations in the EL/BG binary system followed by hydration to form liposomes, respectively. Various properties of liposomes can be readily controlled by changing the polyol concentration. Therefore, the PD method is superior to the conventional method not only in terms of process advantages such as simplicity, ability to achieve mass production, and the absence of toxic organic solvents, but also in terms of suitability for industrial applications.

Multilamellar Liposomes as a Model for Biological Membranes: Saturation Recovery EPR Spin-Labeling Studies.

EPR spin labeling has been used extensively to study lipids in model membranes to understand their structures and dynamics in biological membranes. The lipid multilamellar liposomes, which are the most commonly used biological membrane model, were prepared using film deposition methods and investigated with the continuous wave EPR technique (T2-sensitive spin-labeling methods). These investigations provided knowledge about the orientation of lipids, their rotational and lateral diffusion, and their rate of flip-flop between bilayer leaflets, as well as profiles of membrane hydrophobicity, and are reviewed in many papers and book chapters. In the early 1980s, the saturation recovery EPR technique was introduced to membrane studies. Numerous T1-sensitive spin-label methods were developed to obtain detailed information about the three-dimensional dynamic membrane structure. T1-sensitive methods are advantageous over T2-sensitive methods because the T1 of spin labels (1–10 μs) is 10 to 1000 times longer than the T2, which allows for studies of membrane dynamics in a longer time–space scale. These investigations used multilamellar liposomes also prepared using the rapid solvent exchange method. Here, we review works in which saturation recovery EPR spin-labeling methods were applied to investigate the properties of multilamellar lipid liposomes, and we discuss their relationships to the properties of lipids in biological membranes.

Abstract 5074: Investigating the cellular uptake of liposomal delivery system using cellular models of lymphoma

Abstract Background: Lymphoma accounts for more than 4% of cancer diagnoses in the United States. Conventional treatment strategies for lymphoma are effective, but face a multitude of challenges limiting efficacy. Nanomedicine presents a viable option to optimize the efficacy of current anti-lymphoma therapies. To achieve most selective drug targeting, optimization of liposome preparations is key. To improve the selective targeting properties of conventional liposomes, cell membrane lipid-extracted nanoliposomes (CLENs) were prepared using lipids extracted from lymphoma target cells. Reported here is results of initial design and development, including physicochemical characterization and in vitro analyses. Methods: The CRL-1593.2 cell line was the chosen cellular model of lymphoma. CRL-1593.2 cells were cultured and expanded In vitro for cellular extraction purposes. The CRL-1593.2 cell lipid extract (LE) was included to prepare CRL-1593.2 CLENs. Conventional lipid ingredients used in preparation of CRL-1593.2-CLENs included DOPC, Cholesterol, and DPPE-Rhodamine (used as a fluorescence indicator) for fluorescence studies using a fluorescence microplate reader. Phase I studies included physicochemical characterization and cellular uptake studies of preparations of CLENs, including 0 to 40 mol% of CRL-1593.2 LE content. In Phase II, the optimal LE content as determined by Phase I was fixed, while cholesterol content varied from 0 to 40 mol%.. For in vitro studies, the control cell lines employed represented other hematological diseases, RPMI 8226 (multiple myeloma), CCRF-CEM (acute lymphoblastic leukemia), and K562-GFP (chronic myeloid leukemia). Results: The optimized composition of CLEN preparation type consisted of DOPC: Cholesterol, lymphoma lipid extract (derived from CRL-1593.2 cells) in the ratio of 93:5:2. The mean particle size was 116 ± 10 nm (n=4) and the mean zeta potential was - 4.5 ± 5 mV (n= 4). For in vitro studies, the inclusion of 2 mol% LE in CRL-1593.2-CLENS demonstrated significant uptake when compared to 0% LE control preparations (P = 0.016). Additionally, the lymphoma cells also had a significantly higher uptake of the CRL-1593.2-CLENs when compared to the other hematological cell lines [(CCL-155; P = 0.0081), (K562-GFP; P = 0.0037) and, (CCRF-CEM; P = 0.0079)]. Conclusions: Early findings collectively suggest that the CRL-1593.2-CLENs is a highly selective drug delivery platform for the targeting of lymphoma cells. Citation Format: Joyce Edlyne Chima Bom, Tien Van Le, Tracy Togba-Bass, Erica Kim, Robert Campbell. Investigating the cellular uptake of liposomal delivery system using cellular models of lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5074.

The effect of antifibrotic and antibacterial drugs on the physicochemical properties of liposomes: A spectral study

The effect of antifibrotic and antibacterial drugs on the physicochemical properties of liposomes: A spectral study

Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery-Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes.

New carriers of phytosterols; acylglycerols containing natural myristic acid at sn-1 and sn-3 positions and stigmasterol residue linked to sn-2 position by carbonate and succinate linker have been designed and synthesized in three-step synthesis from dihydroxyacetone (DHA). The synthetic pathway involved Steglich esterification of DHA with myristic acid; reduction of carbonyl group of 1,3-dimyristoylpropanone and esterification of 1,3-dimyristoylglicerol with stigmasterol chloroformate or stigmasterol hemisuccinate. The structure of the obtained hybrids was established by the spectroscopic methods (NMR; IR; HRMS). Obtained hybrid molecules were used to form new liposomes in the mixture with model phospholipid and their effect on their physicochemical properties was determined, including the polarity, fluidity, and main phase transition of liposomes using differential scanning calorimetry and fluorimetric methods. The results confirm the significant effect of both stigmasterol-containing acylglycerols on the hydrophilic and hydrophobic region of liposome membranes. They significantly increase the order in the polar heads of the lipid bilayer and increase the rigidity in the hydrophobic region. Moreover, the presence of both acylglycerols in the membranes shifts the temperature of the main phase transition towards higher temperatures. Our results indicate stabilization of the bilayer over a wide temperature range (above and below the phase transition temperature), which in addition to the beneficial effects of phytosterols on human health makes them more attractive components of novel lipid nanocarriers compared to cholesterol.

Liposomes loaded with betel leaf (Piper betle L.) extract: Antibacterial activity and preservative effect in combination with hurdle technologies on tilapia slices

Betel (Piper betle L.) leaf ethanolic extract (BLEE) has shown to possess antibacterial activities. However, the use of BLEE is still limited due to the instability and remaining chlorophylls even after dechlorophyllization. Encapsulation using liposomes might enhance its stability and reduce the color of BLEE, but antibacterial properties of liposomes have not been elucidated. Hence, this study was conducted to determine the antibacterial activity of liposome loaded with BLEE (L/BLEE). Microbial challenge tests using the selected bacteria (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Shigella sonnei) were also conducted to evaluate the preservative properties of L/BLEE at different concentrations combined with modified atmosphere packaging (MAP) and non-thermal plasma (NTP) treatment on tilapia slices stored at 4 °C. Antibacterial activity of BLEE was enhanced (p < 0.05) after loading into liposomes, as witnessed by lower (p < 0.05) MIC and MBC than those of the unencapsulated BLEE. L/BLEE also showed larger inhibition zones, lower triphenyl-2H tetrazolium chloride (TTC) dehydrogenase activity, and higher release rates of K+ and Mg2+ ions (p < 0.05) of bacteria. Additionally, scanning electron microscopic (SEM) images showed deformations and perforation on cell walls of bacteria after treatment with L/BLEE. L/BLEE at 400 ppm combined with MAP (CO2: Ar: O2 = 60: 30: 10) and NTP (80 KV-RMS for 5 min) exhibited the highest inhibition effect (p < 0.05) toward all the challenged bacteria over 15 days of storage at 4 °C. The use of L/BLEE at 400 ppm combined with MAP and NTP treatments could preserve tilapia slices for up to 12 days.

Polymer-Modified Liposomes for Drug Delivery: From Fundamentals to Applications.

Liposomes are highly advantageous platforms for drug delivery. To improve the colloidal stability and avoid rapid uptake by the mononuclear phagocytic system of conventional liposomes while controlling the release of encapsulated agents, modification of liposomes with well-designed polymers to modulate the physiological, particularly the interfacial properties of the drug carriers, has been intensively investigated. Briefly, polymers are incorporated into liposomes mainly using “grafting” or “coating”, defined according to the configuration of polymers at the surface. Polymer-modified liposomes preserve the advantages of liposomes as drug-delivery carriers and possess specific functionality from the polymers, such as long circulation, precise targeting, and stimulus-responsiveness, thereby resulting in improved pharmacokinetics, biodistribution, toxicity, and therapeutic efficacy. In this review, we summarize the progress in polymer-modified liposomes for drug delivery, focusing on the change in physiological properties of liposomes and factors influencing the overall therapeutic efficacy.

Nose-to-brain/spinal cord delivery kinetics of liposomes with different surface properties

The administration of liposomes via nose-to-brain delivery is expected to become a strategy for efficient drug delivery to the central nervous system. Efficient nose-to-brain delivery and the kinetics of drugs administered in this manner depend on the properties of liposomes. However, there is a lack of basic knowledge of which liposomes are suitable for this purpose. Here, a qualitative study of intranasally administered liposomes (positively charged, neutral, and negatively charged, with or without polyethylene glycol [PEG] modification; particle size <100 nm) was performed to elucidate their dynamics in the brain and spinal cord. Additionally, a quantitative investigation was performed to ascertain their distribution in each part of the brain and spinal cord. The effects of liposome surface charge and PEG modification on the kinetics and distribution post intranasal administration were investigated via two experiments. Qualitative evaluation was performed via ex vivo observation after intranasal administration of fluorescently labeled liposomes. Neutral PEG-modified liposomes were distributed throughout the brain and spinal cord 60 min after administration, and the fluorescence intensity increased with time. By contrast, non-PEG-modified neutral liposomes showed particularly strong fluorescence in the olfactory bulb, and the fluorescence was localized in the anterior part of the brain. Positively charged liposomes showed low fluorescence around the lateral part of the brain and lumbar spinal cord 60 min after administration. Low fluorescence was observed in the whole brain and spinal cord, with strong fluorescence being observed in the olfactory bulb after 120 min of administration. Negatively charged liposomes showed no fluorescence at 60 min after administration, but low fluorescence was observed throughout the brain and spinal cord 120 min after administration. We quantified the radioactivity in the brain and spinal cord after intranasal administration of radioisotope-labeled liposomes. Neutral liposomes showed the highest distribution by area under the drug concentration-time curve (AUC60–120) in the brain and spinal cord compared to other liposomes. Compared with negatively charged liposomes, positively charged liposomes had a higher distribution in the olfactory bulb and forebrain, while negatively charged liposomes had a higher distribution in the hindbrain and bulbospinal tract cord. In addition, the distribution of PEG-modified neutral liposomes in the brain and spinal cord was significantly enhanced compared to that of non-PEG-modified neutral liposomes after 90 min of intranasal administration. These results indicate that surface charge and PEG modification strongly affect the efficiency of nose-to-brain delivery kinetics, and that PEG-modified neutral liposomes are excellent carriers for drug delivery to a wide area of the brain and spinal cord.

Pharmaceutical Development and Design of Thermosensitive Liposomes Based on the QbD Approach.

This study aimed to produce thermosensitive liposomes (TSL) by applying the quality by design (QbD) concept. In this paper, our research group collected and studied the parameters that significantly impact the quality of the liposomal product. Thermosensitive liposomes are vesicles used as drug delivery systems that release the active pharmaceutical ingredient in a targeted way at ~40–42 °C, i.e., in local hyperthermia. This study aimed to manufacture thermosensitive liposomes with a diameter of approximately 100 nm. The first TSLs were made from DPPC (1,2-dipalmitoyl-sn-glycerol-3-phosphocholine) and DSPC (1,2-dioctadecanoyl-sn-glycero-3-phosphocholine) phospholipids. Studies showed that the application of different types and ratios of lipids influences the thermal properties of liposomes. In this research, we made thermosensitive liposomes using a PEGylated lipid besides the previously mentioned phospholipids with the thin-film hydration method.

Structurally Related Liposomes Containing N-Oxide Surfactants: Physicochemical Properties and Evaluation of Antimicrobial Activity in Combination with Therapeutically Available Antibiotics.

Although liposomes are largely investigated as drug delivery systems, they can also exert a pharmacological activity if devoid of an active principle as a function of their composition. Specifically, charged liposomes can electrostatically interact with bacterial cells and, in some cases, induce bacterial cell death. Moreover, they also show a high affinity toward bacterial biofilms. We investigated the physicochemical and antimicrobial properties of liposomes formulated with a natural phospholipid and four synthetic l-prolinol-derived surfactants at 9/1 and 8/2 molar ratios. The synthetic components differ in the nature of the polar headgroup (quaternary ammonium salt or N-oxide) and/or the length of the alkyl chain (14 or 16 methylenes). These differences allowed us to investigate the effect of the molecular structure of liposome components on the properties of the aggregates and their ability to interact with bacterial cells. The antimicrobial properties of the different formulations were assessed against Gram-negative and Gram-positive bacteria and fungi. Drug–drug interactions with four classes of available clinical antibiotics were evaluated against Staphylococcus spp. The target of each class of antibiotics plays a pivotal role in exerting a synergistic effect. Our results highlight that the liposomal formulations with an N-oxide moiety are required for the antibacterial activity against Gram-positive bacteria. In particular, we observed a synergism between oxacillin and liposomes containing 20 molar percentage of N-oxide surfactants onStaphylococcus haemolyticus, Staphylococcus epidermidis, andStaphylococcus aureus. In the case of liposomes containing 20 molar percentage of the N-oxide surfactant with 14 carbon atoms in the alkyl chain for S. epidermidis, the minimum inhibitory concentration was 0.125 μg/mL, well below the breakpoint value of the antibiotic.