Liposome Structure Research Articles

Microfluidic Fabricated Liposomes for Nutlin-3a Ocular Delivery as Potential Candidate for Proliferative Vitreoretinal Diseases Treatment.

Proliferative vitreoretinal diseases (PVDs) represent a heterogeneous group of pathologies characterized by the presence of retinal proliferative membranes, in whose development retinal pigment epithelium (RPE) is deeply involved. As the only effective treatment for PVDs at present is surgery, we aimed to investigate the potential therapeutic activity of Nutlin-3a, a small non-genotoxic inhibitor of the MDM2/p53 interaction, on ARPE-19 cell line and on human RPE primary cells, as in vitro models of RPE and, more importantly, to formulate and evaluate Nutlin-3a loaded liposomes designed for ophthalmic administration. Liposomes were produced using an innovative approach by a microfluidic device under selection of different conditions. Liposome size distribution was evaluated by photon correlation spectroscopy and centrifugal field flow fractionation, while the liposome structure was studied by transmission electron microscopy and Fourier-transform infrared spectroscopy. The Nutlin-3a entrapment capacity was evaluated by ultrafiltration and HPLC. Nutlin-3a biological effectiveness as a solution or loaded in liposomes was evaluated by viability, proliferation, apoptosis and migration assays and by morphological analysis. The microfluidic formulative study enabled the selection of liposomes composed of phosphatidylcholine (PC) 5.4 or 8.2 mg/mL and 10% ethanol, characterized by roundish vesicular structures with 150-250 nm mean diameters. Particularly, liposomes based on the lower PC concentration were characterized by higher stability. Nutlin-3a was effectively encapsulated in liposomes and was able to induce a significant reduction of viability and migration in RPE cell models. Our results lay the basis for a possible use of liposomes for the ocular delivery of Nutlin-3a.

Acidic ionic liquid-based liposome for efficient catalytic degradation of azo dyes

Amphiphilic ionic liquids (ILs) with an imidazole head and two undecene tails (abbreviated as [MimV11, V11]Br) were synthesized through alkylation reaction. They were utilized as lipoid monomers for constructing an isotropic catalytic degradation platform of azo dyes. The spherical structure of this IL-based liposome was reinforced by cross-linking polymerization of the olefin tails. The imidazole groups served as anchor points for attaching catalytic heteropolyanions (such as [PW12O40]3-, [PMo12O40]3-) to the liposomal vehicle. Furthermore, the arrangement of these linkers on the liposome surface facilitated the trapping and enrichment of the catalytic species. Consequently, a series of isotropic catalysts decorated with heteropolyanions (poly[MimA11, A11][heteropolyanions]) were prepared through anion exchange, where sufficiently exposed heteropolyanions maximized the catalytic degradation activity. The morphology, structure, and properties of the catalysts were confirmed using SEM, TEM, FTIR, XPS, UV–vis, and GC–MS. Experimental results found that poly[MimA11, A11][PW12O40] was the optimal catalyst, achieving a removal efficiency of 97.2% for methyl orange (MO) within 3 h. The intermediates involved in the reaction were analyzed to propose the degradation pathway of MO. Moreover, this kind of solid catalyst could be recovered by centrifugation, and its degradation efficiency remained above 91% even after five cycles. This research provides valuable insights for expanding the applications of IL-functionalized materials.

Light emitting diode (LED) irradiation of liposomes enhances drug encapsulation and delivery for improved cancer eradication

Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.

Repurposing Disulfiram to Combat Acute Respiratory Distress Syndrome with Targeted Delivery by LET-Functionalized Nanoplatforms.

Acute respiratory distress syndrome (ARDS) is a serious respiratory condition characterized by a damaged pulmonary endothelial barrier that causes protein-rich lung edema, an influx of proinflammatory cells, and treatment-resistant hypoxemia. Damage to pulmonary endothelial cells and inflammation are pivotal in ARDS development with a key role played by endothelial cell pyroptosis. Disulfiram (DSF), a drug that has long been used to treat alcohol addiction, has recently been identified as a potent inhibitor of gasdermin D (GSDMD)-induced pore formation and can thus prevent pyroptosis and inflammatory cytokine release. These findings indicate that DSF is a promising treatment for inflammatory disorders. However, addressing the challenge posed by its intrinsic physicochemical properties, which hinder intravenous administration, and effective delivery to pulmonary vascular endothelial cells are crucial. Herein, we used biocompatible liposomes incorporating a lung endothelial cell-targeted peptide (CGSPGWVRC) to produce DSF-loaded nanoparticles (DTP-LET@DSF NPs) for targeted delivery and reactive oxygen species-responsive release facilitated by the inclusion of thioketal (TK) within the liposomal structure. After intravenous administration, DTP-LET@DSF NPs exhibited excellent cytocompatibility and minor systemic toxicity, effectively inhibited pyroptosis, mitigated lipopolysaccharide (LPS)-induced ARDS, and prevented cytokine storms resulting from excessive immune reactions in ARDS mice. This study presents a straightforward nanoplatform for ARDS treatment that potentially paves the way for the clinical use of this nanomedicine.

Effect of Penetration Enhancer on the Structure of Stratum Corneum: On-Site Study by Confocal Polarized Raman Imaging.

Keratin and lipid structures in the stratum corneum (SC) are closely related to the SC barrier function. The application of penetration enhancers (PEs) disrupts the structure of SC, thereby promoting infiltration. To quantify these PE-induced structural changes in SC, we used confocal Raman imaging (CRI) and polarized Raman imaging (PRI) to explore the integrity and continuity of keratin and lipid structures in SC. The results showed that water is the safest PE and that oleic acid (OA), sodium dodecyl sulfate (SDS), and low molecular weight protamine (LMWP) disrupted the ordered structure of keratin, while azone and liposomes had less of an effect on keratin. Azone, OA, and SDS also led to significant changes in lipid structure, while LMWP and liposomes had less of an effect. Establishing this non-invasive and efficient strategy will provide new insights into transdermal drug delivery and skin health management.

Light Sensitive Liposomes: A Novel Strategy for Targeted Drug Delivery.

Light-sensitive liposomes have emerged as a promising platform for drug delivery, offering the potential for precise control over drug release and targeted therapy. These lipid-based nanoparticles possess photoresponsive properties, allowing them to undergo structural changes or release therapeutic payloads upon exposure to specific wavelengths of light. This review presents an overview of the design principles, fabrication methods, and applications of light-sensitive liposomes in drug delivery. Further, this article also discusses the incorporation of light-sensitive moieties, such as azobenzene, spiropyran, and diarylethene, into liposomal structures, enabling spatiotemporal control over drug release. The utilization of photosensitizers and imaging agents to enhance the functionality and versatility of light-sensitive liposomes is also highlighted. Finally, the recent advances, challenges, and future directions in the field, emphasizing the potential for these innovative nanocarriers to revolutionize targeted therapeutics, are also discussed.

Construction Strategy of Functionalized Liposomes and Multidimensional Application.

Liposomes are widely used in the biological field due to their good biocompatibility and surface modification properties. With the development of biochemistry and material science, many liposome structures and their surface functional components have been modified and optimized one by one, pushing the liposome platform from traditional to functionalized and intelligent, which will better satisfy and expand the needs of scientific research. However, a main limiting factor effecting the efficiency of liposomes is the complicated environmental conditions in the living body. Currently, in order to overcome the above problem, functionalized liposomes have become a very promising strategy. In this paper, binding strategies of liposomes with four main functional elements, namely nucleic acids, antibodies, peptides, and stimuli-responsive motif have been summarized for the first time. In addition, based on the construction characteristics of functionalized liposomes, such as drug-carrying, targeting, long-circulating, and stimulus-responsive properties, a comprehensive overview of their features and respective research progress are presented. Finally, the paper critically presents the limitations of these functionalized liposomes in the current applications and also prospectively suggests the future development directions, aiming to accelerate realization of their industrialization.

The novel lactoferrin and DHA-codelivered liposomes with different membrane structures: Fabrication, in vitro infant digestion, and suckling pig intestinal organoid absorption

Inspired by membrane structure of breast milk and infant formula fat globules, four liposomes with different particle size (large and small) and compositions (Single phospholipids contained phosphatidylcholine, complex phospholipids contained phosphatidylcholine, phosphatidylethanolamine and sphingomyelin) were fabricated to deliver lactoferrin and DHA. In vitro infant semi-dynamic digestive behavior and absorption in intestinal organoids of liposomes were investigated. Liposomal structures were negligible changed during semi-dynamic gastric digestion while damaged in intestine. Liposomal degradation rate was primarily influenced by particle size, and complex phospholipids accelerated DHA hydrolysis. The release rate of DHA (91.7 ± 1.3 %) in small-sized liposomes (0.181 ± 0.001 μm) was higher than free DHA (unencapsulated, 64.6 ± 3.4 %). Complex phospholipids liposomal digesta exhibited higher transport efficiency (3.4-fold for fatty acids and 2.0-fold for amino acids) and better organoid growth than digesta of bare nutrients. This study provided new insights into membrane structure-functionality relationship of liposomes and may aid in the development of novel infant nutrient carriers.

The urolithin B nanomicellar delivery system as an efficient selective anticancer compound.

Urolithin B (UB), the antioxidant polyphenol has a protective impact on several organs against oxidative stress. However, its bioactivity is limited by its hydrophobic structure. In the current study, UB was encapsulated into a liposomal structure to improve its bioactivities anticancer, and antimicrobial potential. The UB nano-emulsions (UB-NE) were synthesized and characterized utilizing FESEM, DLS, FTIR, and Zeta-potential analysis. The UB-NMs' selective toxicity was studied by conducting an MTT assay on MCF-7, PANC, AGS, and ASPC1 cells. The AO/PI analysis verified the UB-NMs' cytotoxicity on ASPC1 cell lines and approved the MTT results. Finally, the antibacterial activity of the UB-NMs was studied on both gram-positive (B. subtilis, S. aureus) and gram-negative (E. Coli, P. aeruginosa) bacteria by conducting MIC and MBC analysis. The 68.15nm UB-NMs did not reduce the normal HDF cells' survival. However, they reduced the cancer cells' (PANC and AGS cell lines) survival at high treatment concentrations (> 250µg/mL) compared with normal HDF and cancer MCF-7 cells. Moreover, the IC50 doses of UB-NMs for the ASPC1 and PANC cancer cells were measured at 44.87, and 221.02µg/mL, respectively. The UB-NMs selectively exhibited apoptotic-mediated cytotoxicity on the human pancreatic tumor cell line (ASPC1) by down-regulating BCL2 and NFKB gene expression. Also, the BAX gene expression was up-regulated in the ASPC1-treated cells. Moreover, they exhibited significant anti-bactericidal activity against the E. coli (MIC = 50µg/mL, MBC = 150µg/mL), P. aeruginosa (MIC = 75µg/mL, MBC = 275µg/mL), B. subtilis (MIC = 125µg/mL, MBC = 450µg/mL), and S. aureus (MIC = 50µg/mL, MBC = 200µg/mL) strains. The significant selective cytotoxic impact of the UB-NMs on the human pancreatic tumor cell line makes it an applicable anti-pancreatic cancer compound. Moreover, the antibacterial activity of UB-NMs has the potential to decrease bacterial-mediated pancreatic cancer. However, several bacterial strains and further cancer cell lines are required to verify the UB-NMs' anticancer potential.

Ion Quantitation in Liposomal Products Using RP-HPLC with Charged Aerosol Detection.

Ion concentration in liposomal drugs is important for drug stability and drug release profile. However, quantifying ion concentration in liposomal drugs is challenging due to the absence of chromophores or fluorophores of ions and the efficiency of their release from the liposome structure. To address these issues, a method based on reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with a charged aerosol detector (CAD) has been developed to determine total, internal, and external ions in drug-loaded liposomal products. In this protocol, we focused on the quantitation of ammonium and sulfate ions in liposomal products, using generic PEGylated liposomal doxorubicin as an example. This method can be extended to calcium, acetate, and other ions in different liposomal formulations with slight modifications.

Understanding the effects of ethanol on the liposome bilayer structure using microfluidic-based time-resolved small-angle X-ray scattering and molecular dynamics simulations.

Lipid nanoparticles (LNPs) are essential carrier particles in drug delivery systems, particularly in ribonucleic acid delivery. In preparing lipid-based nanoparticles, microfluidic-based ethanol injection may produce precisely size-controlled nanoparticles. Ethanol is critical in LNP formation and post-treatment processes and affects liposome size, structure, lamellarity, and drug-loading efficiency. However, the effects of time-dependent changes in the ethanol concentration on the structural dynamics of liposomes are not clearly understood. Herein, we investigated ethanol-induced lipid bilayer changes in liposomes on a time scale from microseconds to tens of seconds using a microfluidic-based small-angle X-ray scattering (SAXS) measurement system coupled with molecular dynamics (MD) simulations. The time-resolved SAXS measurement system revealed that single unilamellar liposomes were converted to multilamellar liposomes within 0.8 s of contact with ethanol, and the d-spacing was decreased from 6.1 (w/o ethanol) to 4.4 nm (80% ethanol) with increasing ethanol concentration. We conducted 1 μs MD simulations to understand the molecular-level structural changes in the liposomes. The MD simulations revealed that the changes in the lamellar structure caused by ethanol at the molecular level could explain the structural changes in the liposomes observed via time-resolved SAXS. Therefore, the post-treatment process to remove residual ethanol is critical in liposome formation.

A brief overview of quality by design approach for developing pharmaceutical liposomes as nano-sized parenteral drug delivery systems

Bilayer liposome structure with encapsulated hydrophilic drug in the aqueous core.

Encapsulation of propranolol hydrochloride drug using nanoliposome coatings

This study investigated the encapsulation of propranolol hydrochloride drug using nanoliposome coatings prepared by a magnetic stirring method. The encapsulation efficiency was determined using a UV–vis spectrophotometer, and the morphology of the propranolol-loaded liposomes was examined by electron microscopy. The results showed that propranolol hydrochloride can be effectively encapsulated in liposomes with a capsule percentage exceeding 70 %. The composition of the lipids used in the liposome structure played a crucial role in the solubility of the encapsulated drug. The relatively good solubility of propranolol allowed for its better entrapment within the aqueous part of the liposomes. The encapsulation of propranolol hydrochloride within liposomal coatings is expected to improve the stability of the drug in the body and significantly reduce its release until it reaches the target organ. The prepared liposomes exhibited a particle diameter between 20 and 100 nm, making them suitable for intravenous drug delivery. The findings suggest that nanoliposome coatings are a promising strategy for the controlled delivery of propranolol hydrochloride.

Layer-by-layer self-assembled liposomes prepared using sodium alginate and chitosan: Insights into vesicle characteristics and physicochemical stability

In this study, layer-by-layer self-assembled liposomes were prepared with different mixing ratios (3:7, 1:1, and 7:3) of sodium alginate (SA) and chitosan (CS), and the morphology, structure, and physicochemical properties of liposomes after layer-by-layer coating were investigated. After coating the liposomes with SA-CS layer-by-layer (S–C-L), the particle size of liposomes increased from 244.50 to 423.33 nm, the potential changed from negative to positive to 21.20 mV, and the PDI was only 0.393. In the S–C-L 7:3 formulation, the liposomes were uniformly distributed and spherical in size with a clear fingerprint structure. In addition, S–C-L reduced the number of hydrophobic regions within the molecule, allowing the phospholipid molecules to bind tightly into stacks, thus making the liposomes more stable. The S–C-L 7:3 formulation effectively improved the tolerance of liposomes to strong acids and bases, high-salt environments, and UV exposure, and maintained a constant particle size of 400 nm after 28 days of storage. The findings of this study might contribute to the development of polysaccharide layer-by-layer modification of liposomes for a more stable liposomal transport system.

A Phase 1b/2 Trial of Liposomal Cytarabine and Daunorubicin (CPX-351) in Intermediate to High-Risk Acute Myeloid Leukemia for Patients Who Have Failed an Initial Cycle of Induction Chemotherapy

Introduction Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with a high rate of recurrence following standard chemotherapy that continues to have a poor prognosis. While there have been numerous recent advances in the treatment of AML, seven days of continuous infusion cytarabine combined with three doses of an anthracycline medication (7+3) remains the most common backbone treatment for younger (<60) patients. Following 7+3 treatment, patients are typically assessed by a bone marrow biopsy 14-21 days after initial treatment, and 20%-30% of patients will have persistent disease at this time. This residual disease is typically treated with an additional round of the same induction treatment at a full or slightly reduced dose. Unfortunately, a complete response (CR) following re-induction is infrequent in intermediate and high-risk AML patients (CR rates of 35% and 18%, respectively). We have performed mass cytometry studies of AML cell cycle state and find that in patients with residual disease at day 14-21 of induction, leukemia stem and progenitor cells have a low proliferative fraction. We hypothesize that this low rate of proliferation reduces the effectiveness of re-induction therapy and could be countered using CPX-351, which is FDA-approved for treatment of therapy-related AML and AML with myelodysplasia-related changes. CPX-351 is a formulation of cytarabine and daunorubicin in a liposomal structure at an optimal 5:1 molar ratio that has been shown to be preferentially absorbed by hematopoietic cells and to persist in serum and bone marrow for significantly longer than traditional 7+3 chemotherapy. We hypothesize that the unique properties of CPX-351 will better target quiescent leukemia stem and progenitor cells and we thus designed a phase 1b/2 study to determine the safety and efficacy of CPX-351 as re-induction treatment for patients with intermediate and high-risk AML with residual disease after a first round of induction. Patients and Methods Eight patients with intermediate or high-risk AML who had failed to achieve hypocellular marrow 14-21 days following initial treatment with traditional 7+3 cytarabine and daunorubicin were treated with CPX-351 re-induction in the phase 1b portion of the study with a CPX-351 dose of daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2 given two or three times every 48 hours. Concomitant midostaurin (days 8-21) was allowed for patients with FLT3 mutations (Patients #1 and #8). Four patients were ELN intermediate-risk and four adverse-risk; mean blast count before re-induction was 45%. Patients were assessed weekly for signs of toxicity and for treatment response. Samples were collected from bone marrow biopsies performed before and after treatment for correlative mass cytometry studies using a 50-antibody panel to determine cell cycle state, intracellular signaling markers, and DNA damage response. Results Of the eight patients treated to date, six received two doses of CPX-351 and two received three doses. Of the six patients receiving two doses, five achieved a morphologic CR (two with residual genetic alterations), and one patient achieved a CRi. Two patients received three doses of CPX-351, with one achieving a PR and the other MLFS. Five of the eight patients were able to proceed to an allogeneic stem cell transplant. Consistent with previous studies of CPX-351, treatment was well-tolerated, almost all grade 3 or 4 toxicities were due to cytopenias (including two DLTs for delayed count recovery) and the only significant drug-related non-hematologic toxicity was a decrease in cardiac ejection fraction in patient #1. All treated patients survived >150 days and all were able to receive additional AML-directed therapy or HSCT after CPX-351 treatment. Due to slow accrual, hematologic toxicity, and the 100% CR/CRi rate in the two-dose group, the trial was amended to use two doses for the phase 2 portion, and an additional study site was opened. Study accrual is ongoing with a target of 20 additional patients in the phase 2 portion. Conclusion This ongoing phase 1b/2 trial of CPX-351 (liposomal cytarabine and daunorubicin) as re-induction treatment for intermediate and high-risk AML has been safe and tolerable with early treatment outcomes that appear to be much better than reported historical controls. Correlative studies by mass cytometry will further establish the mechanistic reasons for the observed responses.

Initial Quenching Efficiency Determines Light-Driven H2 Evolution of [Mo3 S13 ]2- in Lipid Bilayers.

Nature uses reactive components embedded in biological membranes to perform light-driven photosynthesis. Here, a model artificial photosynthetic system for light-driven hydrogen (H2 ) evolution is reported. The system is based on liposomes where amphiphilic ruthenium trisbipyridine based photosensitizer (RuC9 ) and the H2 evolution reaction (HER) catalyst [Mo3 S13 ]2- are embedded in biomimetic phospholipid membranes. When DMPC was used as the main lipid of these light-active liposomes, increased catalytic activity (TONCAT ~200) was observed compared to purely aqueous conditions. Although all tested lipid matrixes, including DMPC, DOPG, DPPC and DOPG liposomes provided similar liposomal structures according to TEM analysis, only DMPC yielded high H2 amounts. In situ scanning electrochemical microscopy (SECM) measurements using Pd microsensors revealed an induction period of around 26 minutes prior to H2 evolution, indicating an activation mechanism which might be induced by the fluid-gel phase transition of DMPC at room temperature. Stern-Volmer-type quenching studies revealed that electron transfer dynamics from the excited state photosensitizer are most efficient in the DMPC lipid environment giving insight for design of artificial photosynthetic systems using lipid bilayer membranes.

AS1411aptamer conjugated liposomes for targeted delivery of arsenic trioxide in mouse xenograft model of melanoma cancer

Development of AS1411aptamer-conjugated liposomes for targeted delivery of arsenic trioxide is the primary goal of this study. AS1411aptamer was used as ligand to target nucleolin, which is highly expressed on the surface of melanoma cancer cells. The targeted liposomes were constructed by the thin film method, and arsenic trioxide was loaded as cobalt (II) hydrogen arsenite (CHA) to increase the loading efficiency and stability of the liposomes. The liposomal structure was characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and field emission scanning electron microscopy (FESEM). In addition, particle sizes and zeta potential of the CHA-loaded liposomes (CHAL) and aptamer-functionalized CHA-loaded liposomes (AP-CHAL) were determined. In vitro cytotoxicity of CHAL and AP-CHAL were evaluated using MTT assay in murine melanoma (B16) and mouse embryonic fibroblast (MEF) cell lines. The encapsulation efficiency of CHAL and AP-CHAL was reported as 60.2 ± 6.5% and 58.7 ± 4.2%, respectively. In vivo antitumor activity of CHAL and AP-CHAL in the B16 tumor-xenograft mouse model was dramatically observed. All mice of both groups survived until the end of treatment and showed body weight gain. The tumor protrusion completely disappeared in 50% of the mice in these groups. Furthermore, histopathology studies demonstrated that CHAL and AP-CHAL did not induce significant toxicity in healthy mice tissues. However, unlike the CHAL group, which showed an initial increase in tumor volume, a specific antitumor effect was observed in the AP-CHAL group from the beginning of treatment. The results showed that AP-CHAL can be used as an effective drug delivery system with high potential in the treatment of solid tumors.

Levan-based bioactive hydrogels containing herbal liposome in treating acute wounds

Hydrogels in active wound care products are 3D polymeric scaffolds that provide the desired moisture balance in the wound area with their high water retention capacity. Thanks to their biocompatible properties, flexible and porous structures, and high hydrophilic properties, they have frequently been preferred in the repair and regeneration of cells and tissues and the controlled release of bioactive substances to the target area. In this study, hydrogel structures were developed for the first time with levan produced by Halomonas elongata 153B halophilic bacteria. Extracts from Plantago lanceolata L., commonly known as a wound herb, which has medicinal importance for cell regeneration, ensuring tissue integrity in a short time and reducing infections in the wound area, were obtained and extract-loaded liposome structures were formed for controlled release into the wound area. The wound healing efficacy of the composite material developed by loading herbal liposomes into levan-based hydrogel structures was evaluated in an in vitro wound model. Thus, a natural, biocompatible, biodegradable, and functional wound care product containing herbal liposomes suitable for both clinical applications and point-of-care use has been developed. The developed bioactive hydrogels are a promising therapeutic approach for the healing of acute wounds. Graphical abstract [Formula: see text]

Co‐axial electrospinning of liposomal propolis loaded gelatin‐zein fibers as a potential wound healing material

AbstractIn this study, propolis extract (PE) was first encapsulated in different liposomal formulations (65–370 nm) with high encapsulation efficiency (68%–93%). The liposomal PE was further embedded in a food‐grade gelatin‐zein core/shell fiber by using the co‐axial electrospinning method. Transmission electron and confocal laser scanning microscopy verified the structure of liposomes and their homogeneous dispersion in fibers. Scanning electron microscopy (SEM) images confirmed the smooth morphologies of core/shell liposomal fibers. The loading of PE in liposomal fibers improved both thermal (differential scanning calorimetry) and textural (elongation at break and tensile strength) properties, and the fibers loaded with more PE provided higher mucoadhesiveness. The PE‐loaded fiber showed higher antimicrobial activity against Staphylococcus aureus. The incorporation of liposomal PE in fiber enhanced the viability of human skin fibroblast (HFF‐1) cells. The adhesion of HFF‐1 cells on fiber was demonstrated by SEM, thus PE‐loaded liposomal fiber could provide an efficient platform for cell growth. The findings of this study proposed that propolis‐loaded liposomal hybrid fibers produced by the co‐axial method can be used as a potential wound healing material.

Small-Angle X-ray Scattering for PEGylated Liposomal Doxorubicin Drugs: An Analytical Model Comparison Study.

Liposomal delivery systems are recognized as efficient and safe platforms for chemotherapeutic agents, with doxorubicin-loaded liposomes being the most representative nanopharmaceuticals. Characterizing the structure of liposomal nanomedicines in high spatial and temporal resolution is critical to analyze and evaluate their stability and efficacy. Small-angle X-ray scattering (SAXS) is a powerful tool increasingly used to investigate liposomal delivery systems. In this study, we chose a Doxil-like PEGylated liposomal doxorubicin (PLD) as an example and characterized the liposomal drug structure using synchrotron SAXS. Classical analytical models, including the spherical-shell or flat-slab geometries with Gaussian or uniform electron density profiles, were used to model the internal structure of the liposomal membrane. A cylinder model was applied to fit the scattering from the drug crystal loaded in the liposomes. The high-resolution structures of the original drug, Caelyx, and a similar research drug prepared in our laboratory were characterized using these analytical models. The structural parameters of PLDs, including the thickness of the liposomal membrane and morphology of the drug crystal, were further compared. The results demonstrated that both spherical-shell and flat-slab geometries with Gaussian electron density distribution were suitable to elucidate the structural features of the liposomal membrane under a certain range of scattering vectors, while models with uniform electron density distribution exhibited poor fitting performance. This study highlights the technical features of SAXS, which provides structural information at the nanoscale for liposomal drugs. The demonstrated methods are reliable and easy-to-use for the structural analysis of liposomal drugs, which are helpful for a broader application of SAXS in the production and regulation of nanopharmaceuticals.