Review
Pharmacology & Pharmacy
Maria Eugenia Meirinhos Cruz, Maria Luisa Corvo, Maria Barbara Martins, Sandra Simoes, Maria Manuela Gaspar
Summary: The concept of drugs has expanded to include macromolecules such as proteins and enzymes as bioagents in pharmaceuticals. Enzymes, in particular, pose challenges in terms of delivery and carrier systems. This review focuses on therapeutic enzymes and their applications, listing examples that have reached the pharmaceutical market. It also addresses problems associated with their clinical use and explores nanotechnological strategies to address these issues. Liposomes, the most well-studied and suitable nanosystem for enzyme delivery in vivo, are discussed as drug delivery systems. Examples of liposomal enzymatic formulations and successful pre-clinical results are extensively discussed.
Article
Chemistry, Multidisciplinary
Thomas Holmstrom, Mette Galsgaard Malle, Shunliang Wu, Knud Jorgen Jensen, Nikos S. Hatzakis, Christian Marcus Pedersen
Summary: This paper introduces a new lipid that can change its conformation based on the presence of Zn2+, triggered by the metal chelator Na(2)EDTA. The lipid was successfully incorporated into stable liposomes and showed potential for releasing the fluorescent cargo through a conformational change.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Physical
Aybike Hemetsberger, Eduard Preis, Konrad Engelhardt, Bernd Gutberlet, Frank Runkel, Udo Bakowsky
Summary: This study investigated the stability of liposomes containing tetraether lipids under different conditions. The results showed that the inclusion of tetraether lipids in liposomes improved their structural stability against high temperature, low pH, sterilization via autoclaving, and the presence of fetal calf serum and lung surfactant.
Article
Pharmacology & Pharmacy
Ping Zhou, Chonghao Chen, Xuan Yue, Jinming Zhang, Chi Huang, Shiyi Zhao, Anxing Wu, Xuebo Li, Yan Qu, Chen Zhang
Summary: The study found that the triptolide liposome-loaded dissolving microneedle system can effectively improve symptoms of osteoarthritis, reduce joint swelling and inflammatory response, and may be a promising treatment option.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Manjari Mishra, Aishi Das Gupta, Ruchika Dadhich, Mohammad Naiyaz Ahmad, Arunava Dasgupta, Sidharth Chopra, Shobhna Kapoor
Summary: This study demonstrates that liposomes constituted with immunostimulatory lipids from Mycobacterium tuberculosis can modulate cellular immune response and eradicate pathogens effectively through sustained drug delivery. The study also reveals the pH-dependent release of drugs from liposomes, their biocompatibility, long-term stability, and antimicrobial efficacy in vitro and intracellularly. This work provides a proof-of-concept for the utilization of liposomes derived from the pathogen itself to achieve dual action (drug delivery and immunomodulation) for effective eradication.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Claudia Bonechi, Fariba Fahmideh Mahdizadeh, Luigi Talarico, Simone Pepi, Gabriella Tamasi, Gemma Leone, Marco Consumi, Alessandro Donati, Agnese Magnani
Summary: Glaucoma, a group of neurodegenerative diseases, is the second leading cause of irreversible blindness worldwide. The limited penetration of drugs through the ocular barrier reduces the systemic bioavailability, leading to the need for frequent drug administration and potential toxic effects. Liposomes and other novel drug-delivery systems can enhance the therapeutic efficacy of antiglaucomatous drugs by improving drug penetration, bioavailability, sustained release, tissue targeting, and reduction in intraocular pressure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Douweh Leyla Gbian, Abdelwahab Omri
Summary: This article extensively discusses the physicochemical properties, formulation methods, characteristics, mechanisms of action, and large-scale manufacturing of liposomes as delivery systems, as well as the benefits, toxicity, and limitations of their use in pharmacotherapeutics. It also describes experimental approaches to reduce or bypass the drawbacks of liposomal drugs and discusses their application in the treatment of various diseases.
Article
Pharmacology & Pharmacy
Leila Mousavifar, Jordan D. Lewicky, Alexis Taponard, Rahul Bagul, Madleen Rivat, Shuay Abdullayev, Alexandrine L. Martel, Nya L. Fraleigh, Arnaldo Nakamura, Frederic J. Veyrier, Hoang-Thanh Le, Rene Roy
Summary: This study reports the chemical synthesis of a novel series of mannosylated neoglycolipids with the goal of further improving on the previous glyconanoparticles. By using a new synthetic method, stable neoglycoliposomes were successfully prepared, and their potential applications in improving cellular uptake and biological activity were explored.
Article
Chemistry, Medicinal
Thibaud Bailly, Sacha Bodin, Victor Goncalves, Franck Denat, Clement Morgat, Aurelie Prignon, Ibai E. Valverde
Summary: Bivalent ligands, with two ligands covalently connected by a linker, have gained attention for their pharmacological potential. However, the synthesis, especially of labeled heterobivalent ligands, can be time-consuming. This study presents a simple method for the modular synthesis of labeled heterobivalent ligands, allowing quick access to multiple ligands. The assembly method preserves the tumor targeting properties of the ligands, as demonstrated by the radiolabeled conjugate's biological activity.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Silvia Pisani, Enrica Chiesa, Ida Genta, Rossella Dorati, Marilena Gregorini, Maria Antonietta Grignano, Marina Ramus, Gabriele Ceccarelli, Stefania Croce, Chiara Valsecchi, Manuela Monti, Teresa Rampino, Bice Conti
Summary: This study focuses on formulating liposomes for use in hypothermic isolated kidney dynamic machine perfusion as drug delivery systems to improve organ preservation. Microfluidic techniques are found to be superior for obtaining reproducible spherical liposomes with size below 200 nm. Protein encapsulation efficiency is affected by molecular weight and isoelectric point. Lowering incubation temperature slows down protein release. Liposomes are taken up by epithelial tubular renal cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jinchao Lou, Megan L. Qualls, Michael D. Best
Summary: Liposomes are effective nanocarriers for delivering therapeutic cargo, and recent progress has been made in utilizing strategies such as reversible covalent bonding and caging groups to control liposomal cell delivery. These approaches provide promising avenues for the development of next-generation liposomal therapeutic nanocarriers.
Article
Multidisciplinary Sciences
Stephanie M. Kong, Daniel F. Costa, Anna Jagielska, Krystyn J. Van Vliet, Paula T. Hammond
Summary: The stiffness of nanoparticles plays a crucial role in drug delivery, affecting circulation time, tumor accumulation, and penetration. Layer-by-layer nanoparticles can modulate stiffness by adjusting the mechanical properties of the core, leading to improved tumor targeting and therapeutic outcomes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Xin Wu, Xinmei Chen, Xinyu Wang, Haisheng He, Jianming Chen, Wei Wu
Summary: Paclitaxel-loaded liposomes hold potential for the treatment of breast carcinoma and other cancers. By conjugating paclitaxel with lipids of different chain lengths, the drug release and enzymatic conversion rates can be controlled, affecting the pharmacokinetics, tumor accumulation, and anti-tumor efficacy of liposomal paclitaxel.
CHINESE CHEMICAL LETTERS
(2024)
Article
Biochemistry & Molecular Biology
Richard Wibel, Doris E. Braun, Laurenz Haemmerle, Arne M. Joergensen, Patrick Knoll, Willi Salvenmoser, Christian Steinbring, Andreas Bernkop-Schnuerch
Summary: In this study, thiolated chitosan was used as a coating material for solid lipid nanoparticles, with the protection of thiol groups playing a key role in their interaction with mucosa. Different coating materials showed varying effects on mucus interaction and diffusion behavior on intestinal mucosa.
Review
Pharmacology & Pharmacy
Diana Guimaraes, Artur Cavaco-Paulo, Eugenia Nogueira
Summary: Liposomes are effective drug delivery systems that improve therapeutic efficacy, being nontoxic and biodegradable. Key aspects such as design, production techniques, drug loading, and characterization for in vitro and in vivo performance are essential for successful liposomal formulations. Other topics explored include functionalization, targeting strategies, stability, limitations, and current market applications of liposomes in various therapeutic fields.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Biochemical Research Methods
Ruhani Sagar, Jinchao Lou, Alexa J. Watson, Michael D. Best
Summary: The use of synthetic lipid switches designed to respond to zinc ions enables zinc-triggered release of liposomal contents. Experimental results demonstrate that zinc treatment leads to morphological changes in lipid nanoparticles and complexation of zinc ions with ZRLs.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Chemistry, Physical
Megan L. Qualls, Ruhani Sagar, Jinchao Lou, Michael D. Best
Summary: The ability to modulate lipid membrane structures based on understanding of lipid self-assembly properties has led to exciting biological applications. This includes controlled liposome decomposition for triggered cargo release using synthetic lipid switches, and the in situ formation of lipid bilayer membranes for artificial cell development. Both endeavors rely on common principles of lipid self-assembly but achieve completely opposite results.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Multidisciplinary
Jinchao Lou, Jennifer A. Schuster, Francisco N. Barrera, Michael D. Best
Summary: This study reports a stimuli-responsive liposome delivery strategy based on phosphorylated small molecules. The researchers designed and synthesized lipid switches with two ZnDPA units, which successfully achieved selective cargo release in the presence of ATP. Cellular delivery analysis using fluorescence microscopy and pharmacological ATP manipulation confirmed the specificity of liposome delivery, which increased with intracellular ATP accumulation and was inhibited by ATP downregulation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Amber L. H. Gray, Michael R. Sawaya, Debalina Acharyya, Jinchao Lou, Emery M. Edington, Michael D. Best, Rebecca A. Prosser, David S. Eisenberg, Thanh D. Do
Summary: Understanding the atomic structures of amyloid oligomers is crucial for investigating neurodegenerative diseases, such as Alzheimer's disease. The G6W mutation in the hexameric amyloid model KV11 resulted in an asymmetric dodecamer with unique structural features that may disrupt lipid transport and selectively affect certain brain regions. This study provides insights into how the G6W mutation initiates cellular injury through neuropeptides released from brain slices, shedding light on potential therapeutic targets for neurodegenerative diseases.
Article
Chemistry, Multidisciplinary
Jinchao Lou, Megan L. Qualls, Macy M. Hudson, Dillon P. McBee, Joshua A. Baccile, Michael D. Best
Summary: We report the development of boronate-caged guanidine-lipid 1, which can activate liposomes for cellular delivery by reactive oxygen species (ROS). The boronate cage enhances the selectivity of cell entry, only allowing activation in the presence of ROS. The uncaging of boronate by hydrogen peroxide was confirmed by mass spectrometry and zeta potential measurements. Fluorescence microscopy showed significant enhancements in cellular delivery when 1-liposomes were incubated with hydrogen peroxide. The study highlights the potential of lipid 1 as an ROS-responsive liposomal platform for targeted drug delivery.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Megan L. Qualls, Jinchao Lou, Dillon P. McBee, Joshua A. Baccile, Michael D. Best
Summary: This study reports a liposome platform incorporating a cyclic disulfide lipid (CDL) to enhance cell entry and functionalize the liposome membrane. The results demonstrate that this liposome system enables convenient membrane decoration through reaction with thiol-functionalized small molecules and significantly enhances cellular delivery when incorporated within liposomes.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Review
Chemistry, Multidisciplinary
Jinchao Lou, Ruhani Sagar, Michael D. Best
Summary: This article describes recent advancements in the development of stimuli-responsive liposomes through programmable changes to lipid self-assembly properties, which can drive the release of encapsulated contents. These smart liposomal platforms selectively respond to ions or small molecules that are commonly overproduced by diseased cells, providing an important addition to the toolbox for controlled cargo release.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jinchao Lou, Megan L. Qualls, Michael D. Best
Summary: Liposomes are effective nanocarriers for delivering therapeutic cargo, and recent progress has been made in utilizing strategies such as reversible covalent bonding and caging groups to control liposomal cell delivery. These approaches provide promising avenues for the development of next-generation liposomal therapeutic nanocarriers.
Article
Biochemistry & Molecular Biology
Megan L. Qualls, Hannah Hagewood, Jinchao Lou, Samuel Mattern-Schain, Xiaoyu Zhang, Deidra J. Mountain, Michael D. Best
Summary: Liposomes are effective therapeutic nanocarriers that can encapsulate and enhance the properties of various drugs and diagnostic agents. They have the potential to target cell membrane glycans, which are commonly dysregulated in diseased cells, by incorporating bis-boronic acid lipids (BBALs) in order to achieve selective saccharide sensing and enhance cell surface recognition.
Article
Chemistry, Organic
Ruhani Sagar, Emily A. Jaremba, Jinchao Lou, Michael D. Best
Summary: In this work, we demonstrate the release of content from liposomes triggered by copper chelation to a synthetic lipid switch. We show that carboxyfluorescein dye cargo is released upon copper treatment and that liposomal release can be controlled by varying copper abundance. Furthermore, our results indicate that this platform specifically responds to copper and leads to significant changes in liposome properties.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ruhani Sagar, Jinchao Lou, Michael D. Best
Summary: In this work, a bis-pyrene phospholipid probe was designed, synthesized, and applied for the detection of phospholipase A2 (PLA2) activity. The probe exhibited changes in pyrene monomer and excimer fluorescence intensities upon PLA2 action. Continuous fluorometric assays enabled the detection of multiple PLA2 enzymes and the inhibition of PLA2 activity by p-bromo phenacylbromide. Thin-layer chromatography and mass spectrometry analysis confirmed the hydrolysis of the probe by PLA2. The probe also showed cleavage by phospholipase C and D enzymes, although fluorescence changes were not observed. Overall, the developed bis-pyrene phospholipid probe is effective for the detection of PLA2 activity and can be used for inhibitor screening.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Christelle F. F. Ancajas, Adam J. J. Carr, Jinchao Lou, Ruhani Sagar, Yue Zhou, Todd B. B. Reynolds, Michael D. D. Best
Summary: This study reports the use of clickable monoacylglycerol (MAG) analogs as probe for labeling glycerolipids in lipid metabolism. Azide tags were incorporated into the glycerol region to design probes that can label glycerolipids without being removed. Different acyl chain lengths in clickable MAG probes resulted in varying cell imaging and cytotoxicity profiles. A probe with short acyl chain (C-4-MAG-N-3) was found to infiltrate natural lipid biosynthetic pathways and label neutral and phospholipid products. This work demonstrates the tunability of lipid metabolic labeling profiles and provides valuable tools for studying alterations in lipid metabolism.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Jinchao Lou, Macy M. Hudson, Christelle F. Ancajas, Michael D. Best
Summary: We present stimuli-responsive liposomes that selectively release their contents upon treatment with guanosine triphosphate (GTP) and show significant changes in their self-assembly properties. This platform has the potential for triggered release applications.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Sydney E. Bottcher, Jinchao Lou, Michael D. Best
Summary: A stimuli-responsive liposomal platform selectively activated by IP3 is reported, demonstrating its potential for triggered release and sensing applications.
CHEMICAL COMMUNICATIONS
(2022)