Journal of Liposome Research最新文献

Herein, we describe the synthesis of pH-sensitive lipophilic colchicine prodrugs for liposomal bilayer inclusion, as well as preparation and characterization of presumably stealth PEGylated liposomes with above-mentioned prodrugs. These formulations liberate strongly cytotoxic colchicinoid derivatives selectively under slightly acidic tumor-associated conditions, ensuring tumor-targeted delivery of the compounds. The design of the prodrugs is addressed to pH-triggered release of active compounds in the slight acidic media, that corresponds to tumor microenvironment, while keeping sufficient stability of the whole formulation at physiological pH. Correlations between the structure of the conjugates, their hydrolytic stability, colloidal stability, ability of the prodrug retention in the lipid bilayer are described. Several formulations were found promising for further development and in vivo investigations.

Eugenol, as a natural antibacterial agent, has been widely studied for its inhibitory effect on the common food-borne pathogen Staphylococcus aureus (S. aureus). However, the widespread application of eugenol is still limited by its instability and volatility. Herein, γ-polyglutamic acid coated eugenol cationic liposomes (pGA-ECLPs) were successfully constructed by self-assembly with an average particle size of 170.7 nm and an encapsulation efficiency of 36.2%. The formation of pGA shell significantly improved the stability of liposomes, and the encapsulation efficiency of eugenol only decreased by 20.7% after 30 days of storage at 4 °C. On the other hand, the pGA layer can be hydrolyzed by S. aureus, achieving effective control of release through response to bacterial stimuli. The application experiments further confirmed that pGA-ECLPs effectively prolonged the antibacterial effect of eugenol in fresh chicken without causing obvious sensory effects on the food. The above results of this study provide an important reference for extending the action time of natural antibacterial substances and developing new stimuli-responsive antibacterial systems.

Effective healing and regeneration of various bone defects is still a major challenge and concern in modern medicine. Calcium phosphates have emerged as extensively studied bone substitute materials due to their structural and chemical resemblance to the mineral phase of bone, along with their versatile properties. Calcium phosphates present promising biological characteristics that make them suitable for bone substitution, but a critical limitation lies in their low osteoinductivity. To supplement these materials with properties that promote bone regeneration, prevent infections, and cure bone diseases locally, calcium phosphates can be biologically and therapeutically modified. A promising approach involves combining calcium phosphates with drug-containing liposomes, renowned for their high biocompatibility and ability to provide controlled and sustained drug delivery. Surprisingly, there is a lack of research focused on liposome-calcium phosphate composites, where liposomes are dispersed within a calcium phosphate matrix. This raises the question of why such studies are limited. In order to provide a comprehensive overview of existing liposome and calcium phosphate composites as bioactive substance delivery systems, the authors review the literature exploring the interactions between calcium phosphates and liposomes. Additionally, it seeks to identify potential interactions between calcium ions and liposomes, which may impact the feasibility of developing liposome-containing calcium phosphate composite materials. Liposome capacity to protect bioactive compounds and facilitate localized treatment can be particularly valuable in scenarios involving bone regeneration, infection prevention, and the management of bone diseases. This review explores the implications of liposomes and calcium phosphate material containing liposomes on drug delivery, bioavailability, and stability, offering insights into their advantages.

Breast cancer stem cells (BCSCs) play a key role in therapeutic resistance in breast cancer treatments and disease recurrence. This study aimed to develop a combination therapy loaded with pH-sensitive liposomes to kill both BCSCs and the okbulk cancer cells using trastuzumab-sensitive and resistant human epidermal growth factor receptor 2 positive (HER2⁺) breast cancer cell models. The anti-BCSCs effect and cytotoxicity of all-trans retinoic acid, salinomycin, and bufalin alone or in combination with doxorubicin were compared in HER2⁺ cell line BT-474 and a validated trastuzumab-resistant cell line, BT-474R. The most potent anti-BCSC agent was selected and loaded into a pH-sensitive liposome system. The effects of the liposomal combination on BCSCs and bulk cancer cells were assessed. Compared with BT-474, the aldehyde dehydrogenase positive BCSC population was elevated in BT-474R (3.9 vs. 23.1%). Bufalin was the most potent agent and suppressed tumorigenesis of BCSCs by ∼50%, and showed strong synergism with doxorubicin in both BT-474 and BT-474R cell lines. The liposomal combination of bufalin and doxorubicin significantly reduced the BCSC population size by 85%, and inhibited both tumorigenesis and self-renewal, although it had little effect on the migration and invasiveness. The cytotoxicity against the bulk cancer cells was also enhanced by the liposomal combination than either formulation alone in both cell lines (p < 0.001). The liposomal bufalin and doxorubicin combination therapy may effectively target both BCSCs and bulk cancer cells for a better outcome in trastuzumab-resistant HER2⁺ breast cancer.

Yamanashi et al., conducted a study on the absorption of cholesterol and β-sitosterol, as well as the inhibitory effect of ezetimibe (EZE). They used CaCo-2 cells to simulate the intestines and investigated how different mixed micelles, acting as carriers, were absorbed into these cells through the Niemann-Pick C1-like 1 (NPC1L1) protein. The study focused on the impact of micelle shape, size, and zeta potential on absorption and the inhibitory effect of EZE. I utilized small-angle X-ray scattering and a zeta potential measuring device to measure these characteristics. The findings revealed a two-step mechanism: NPC1L1 selectively bound micelles based on their shape and size, and once bound, the absorption was regulated by the molecular structure of the micelle components. EZE's inhibitory effect changed with micelle composition, influencing micelle size and shape. EZE initially acted on the micelle's shape and size, and then NPC1L1 selectively bound micelles based on their shape and size, allowing EZE to directly inhibit absorption by interacting with NPC1L1. This groundbreaking discovery challenges existing concepts and holds significant implications for researchers in drug development, as well as physicians and pharmacists.

The development of an inhalation powder (IP) for cancer therapy is desired to improve the therapeutic response and patient compliance. The latest studies highlighted that statins, a class of drugs used in hypercholesterolemia, can have anticancer and antiinflammatory properties. Therefore, the aim of the study was to develop an IP containing liposomes loaded with simvastatin using spray drying technology, as well as to investigate the influence of formulation factors on the quality attributes of the IP by means of experimental design. Results highlighted that the composition of liposomes, namely type of phospholipid and cholesterol concentration, highly influences the quality attributes of IP, and the use of optimal concentrations of excipients, i.e. D-mannitol and L-leucine, is essential to preserve the characteristics of liposomes throughout the spray drying process. The in vitro characterization of the optimal IP formulation revealed that the total percentage of released drug is higher from the IP formulation compared to the powder of active substance (53.38 vs. 42.76%) over a period of six hours, and 39.67% of dry particles have a size less than 5 µm, making them suitable for inhalation. As a conclusion, spray drying technology can be effectively used in the development and preparation of IP containing liposomes.

In different types of cancer treatments, cancer-specific T cells are required for effective anticancer immunity, which has a central role in cancer immunotherapy. However, due to the multiple inhibitions of CD8⁺ T cells by tumor-related immune cells, CD8⁺ T-cell mediated antitumor immunotherapy has not achieved breakthrough progress in the treatment of solid tumors. Receptors for sialic acid (SA) are highly expressed in tumor-associated immune cells, so SA-modified nanoparticles are a drug delivery nanoplatform using tumor-associated immune cells as vehicles. To relieve the multiple inhibitions of CD8⁺ T cells by tumor-associated immune cells, we prepared SA-modified doxorubicin liposomes (SL-DOX, Scheme 1A). In our study, free SA decreased the toxicity of SL-DOX to tumor-associated immune cells. Compared with common liposomes, SL-DOX could inhibit tumor growth more effectively. It is worth noting that SL-DOX could not only kill tumor-related neutrophils and monocytes to relieve the multiple inhibitions of CD8⁺ T cells but also induce immunogenic death of tumor cells to promote the infiltration and differentiation of CD8⁺ T cells (Scheme 1B). Therefore, SL-DOX has potential value for the clinical therapeutic effect of CD8⁺ T cells mediating anti-tumor immunotherapy.

As the aging population continues to increase, aging-related inflammation, oxidative stress, and neurodegenerative diseases have become serious global health threats. Resveratrol, a star molecule in natural polyphenols, has been widely reported to have physiological activities such as anti-aging, anti-inflammatory, antioxidant, and neuroprotection. However, its poor water solubility, rapid metabolism, low bioavailability and poor targeting ability, which limits its application. Accordingly, a brain-targeted resveratrol liposome (ANG-RES-LIP) was developed to solve these issues. Experimental results showed that ANG-RES-LIP has a uniform size distribution, good biocompatibility, and a drug encapsulation rate of over 90%. Furthermore, in vitro cell experiments showed that the modification of the targeting ligand ANG significantly increased the capability of RES to cross the BBB and neuronal uptake. Compared with free RES, ANG-RES-LIP demonstrated stronger antioxidant activity and the ability to rescue oxidatively damaged cells from apoptosis. Additionally, ANG-RES-LIP showed the ability to repair damaged neuronal mitochondrial membrane potential. In vivo experiments further demonstrated that ANG-RES-LIP improved cognitive function by reducing oxidative stress and inflammation levels in the brains of aging model mice, repairing damaged neurons and glial cells, and increasing brain-derived neurotrophic factor. In summary, this study not only provides a new method for further development and application of resveratrol but also a promising strategy for preventing and treating age-related neurodegenerative diseases.

'Active targeting' refers to modifying a nanocarrier's surface with targeting ligands. This study introduced an efficient approach for immobilizing imidazole-based drugs onto the metallated-porphyrin complex within the porphysome nanocarrier. To enhance cellular and bacterial uptake, a Ni-porphyrin with a fatty acid tail was synthesized and placed in the bilayer center of DPPC, facilitating receptor-mediated endocytosis. The Ni-porphyrin in the head group of the Ni-porphyrin-tail was placed superficially in the polar region of the membrane. Spherical unilamellar vesicle formation (DPPC: Ni-porphyrin-tail 4:1 mole ratio), as metallo-porphysome, was achieved through supramolecular self-assembly in an aqueous buffer. These vesicles exhibited a diameter of 279 ± 7 nm and a zeta potential of -15.3 ± 2.5 mV, showcasing their unique cytocompatibility. Nitroimidazole was decorated on the surface of metallo-porphysomes and pistachio green hull extract (PGHE) was loaded into the carrier for synergistic activity against (E. coli) and (S. aureus) bacteria strains. The physicochemical properties of Nitroimidazole-porphysome-PGHE, including size, zeta potential, morphology, loading efficiency, and release profile under various pH and temperature conditions in simulated gastrointestinal fluids were characterized. This combination therapy prevented bacterial cell attachment and biofilm formation in Caco-2 cells, as colon epithelial cells. The remarkable benefit of this system is that it does not affect cell viability even at 0.5 mg/ml. This study demonstrates the potential of a new co-delivery system using biocompatible metallo-porphysomes to decrease bacterial infections.

Emtricitabine (FTC) a BCS class I drug, is used for HIV prevention. The high solubility of the drug is the leading cause of severe hepatotoxicity and lactic acidosis. This research focuses on the use of modified pullulan for the preparation of polymeric liposomes of FTC. Modified pullulan was synthesized using cholesterol, and succinic anhydride in a controlled chemical environment. The formation of the polymer was established through analysis of spectra. Varying the drug-polymer ratio (1:1, 1:2, and 1:3), the drug-polymer composite was loaded in the vesicular system of soya phosphatidylcholine and cholesterol. Formulations were evaluated for drug entrapment, particle size, surface morphology, and in vitro and ex vivo drug release. An in vivo study of the pure drug and the best formulation on mice was conducted for 28 days following daily oral administration to evaluate the effect on liver and hematological parameters. The best formulation was further subjected to cytotoxicity study on hepatic cell lines. Spectral analysis confirmed the formation of modified pullulan. All formulations showed high drug entrapment in the nanovesicles. The in vitro and ex vivo drug release profiles depicted a controlled release of the drug. Hematological parameters were found to be under control in the animals throughout the experimentation. A comparative histopathology study on the livers and cytotoxicity study on hepatic cell lines revealed the safety of the best formulation over the pure drug. Hence it can be concluded that polymeric liposomes of FTC can be a promising mode of delivery to overcome its limitations.