Clipos™ Fluorescein Labeled Phosphatidylcholine (PC) Liposomes, Non PEGylated

For the hunt for advanced delivery systems, scientists are still considering ways to introduce drug to specific tissues with as few side effects as possible. Most promising are liposomes and in particular PC-based liposomes, which are so widespread as they are biocompatible, general-purpose and can contain many drugs. When you add in phosphatidylcholine with fluorescein, a fluorescent pigment, fluorescein-tagged PC liposomes can be used not only to transport drugs but to track their in vivo activities. Such liposomes can be observed by fluorescence imaging due to fluorescein infusion revealing in real time the process of biodistribution, cellular uptake and release of the drug embedded. This feature is useful particularly in the research labs where the pharmacokinetic and therapeutic effects of carrier-loaded drugs are important for optimisation of drug delivery systems. Not only are fluorescein-labeled PC liposomes a new instrument for drug detection, they're also an efficient platform for generating targeted drug delivery approaches such as cancer treatment, gene delivery and vaccines. Because PC is one of the building blocks of biological membranes, it was a natural choice for liposomal drug delivery systems. It is a naturally occurring phospholipid that is biocompatible and biodegradable, so PC liposomes are easily tolerated by the body. PC molecules are amphiphilic (that is, they have hydrophobic and hydrophilic domains) and thus, able to build a solid bilayer structure in water. This makes them highly useful to seal hydrophobic as well as hydrophilic therapeutic molecules, from small molecules to large biomolecules like proteins, peptides and nucleic acids. The artificial fluorescein (a strong fluorescent dye) is typically bound to the liposome's lipid bilayer, to make it easier to visualize and quantify liposome abundance in living systems. It's this fluorescent labelling that can be used to not only map liposome fate, but also to map how the liposomes interact with cell membranes, tissues and organs, and understand how they act in complicated biological contexts. Fluorescence of fluorescein-labelled PC liposomes is a novel way to monitor the delivery process non-invasively and in real time. Through fluorescence imaging — either IVIS or confocal microscopy — scientists can see where and how the liposomes are located, at the cellular (or even subcellular) level. This allows for tracking of liposome intake by target cells (like tumor cells) and internalization into endosomes or lysosomes. Furthermore, fluorescein labeling can be used to quantify the stability, integrity and pharmacokinetics of liposomes over time. That sort of continuous monitoring is very useful to see how liposomes are broken down, how long they travel through the blood, and how efficiently they disperse their cargo at the target location. The in vivo monitoring of drug-loaded liposomes will be useful to optimize drug composition and delivery for drug development. Furthermore, fluorescein lets scientists separate the liposomes that have loaded their cargo from those that haven't – which is important information for developing a drug delivery system.

Figure 1. Reduction-responsive release property of egg phosphatidylcholine liposomes incorporating benzyl disulfide. (Huangying Guo, et al.; 2016)

Fluorescein in PC liposomes has several distinct properties that make them useful for drug delivery. Fluorescein is a water-soluble, highly fluorescent material that glows bright green under ultraviolet (UV) or blue light. It's therefore a great candidate for monitoring PC liposomes' distribution in a wide range of biological applications in vitro and in vivo. Fluorescein labeling is very sensitive and it can detect very small amounts of liposomes. This sensitivity is especially important in drug delivery experiments using low concentration liposomal drugs, because we can track liposomes at low concentrations. The fluorescence imaging also allows us to visualize liposomes as they are formed without invasive surgery. It is possible for researchers to see liposome activity in cultured cells or tissues using fluorescence microscopy, or to study liposome distribution in the organism through non-invasive in vivo imaging. This convenience in monitoring is a big improvement on older techniques, which may involve more intrusive methods or less precise mark placement. The other advantage of fluorescein-labeled PC liposomes is that they also deliver the drugs by way of "stealth" of phosphatidylcholine. phosphatidylcholine is added to the liposome membrane which prevents the liposome from being rapidly removed by the immune system. This is the so-called "stealth effect," and it allows the liposomes to circulate longer in the blood, which then gives them time to build up in their target tissues or tumors. This is especially relevant in the context of cancer treatment, where longer-term drug release from liposomes can maximise treatment effectiveness without the side effects associated with standard chemotherapy. As a fluorescent marker, they could monitor liposomes in tumours or other targets, and measure how well the drug delivery system worked. Moreover, the surface of fluorescein-labelled PC liposomes can be customized to include targeting ligands like antibodies or peptides to further optimize the delivery of the drugs to cells or tissues with greater precision and potency. PC liposomes labeled with fluorescein are also an ideal platform for optimising release profiles of capsulated drugs. Fluorescein's fluorescence intensity is a simple way to calculate the amount of encapsulated cargo that is released over time. Based on the fluorescence signal, scientists can track the rate at which the contents of the liposome are dissolved, and observe how pH, temperature and enzymatic activity impact release. This is especially useful when designing controlled release systems, in which you want to get the drug released in a prolonged way. The precision to tune the release profile based on experimental data can enhance therapeutic outcomes of liposomal drug formulations so that the drug is released in the right proportion and at the appropriate time. In cancer therapy, for example, fluorescein-labelled PC liposomes can be made to activate chemotherapeutic drugs by reacting to tumours' acidic milieu and then monitored by fluorescence imaging to establish the right release conditions.

Fluorescein-labeled phosphatidylcholine liposomes have many applications for drug delivery especially in applications that require close tracking and targeted delivery. In cancer therapy, for instance, such liposomes can be used to bind chemotherapeutic drugs to tumours at their most effaced while sparing healthy tissues. The fluorescence feature also allows you to track the volume of liposome in the tumour with real time, to evaluate the drug delivery rate. Also, the surface of the liposomes can be altered with tumor targeting ligands, which increase the specificity of treatment. If scientists can monitor the fluorescence signal, they know if the liposomes are indeed going after the tumour and carrying their cargo in the right direction. This virtual monitoring of the therapy might result in more tailored and successful cancer therapies. Fluorescein-tagged PC liposomes were also used to deliver genes in addition to cancer therapy. Gene therapies, in which the purpose is to insert or manipulate genes into cells to cure disease, usually have problems with the delivery and absorption of the pharmacological DNA or RNA. Liposomes – such as those constructed from phosphatidylcholine – are a secure and reliable way to encapsulate and deliver genetic material to cells. Fluorescein-labeled liposome gene delivery systems are then monitored for intracellular uptake – and that helps us learn about the way liposomes pass across cell membranes, enter the cell, and release their genome. This live tracking can improve the delivery efficiency and the success of gene therapy treatments. Fluorescein-tagged PC liposomes also have potential for vaccines. These liposomes are perfect candidates for vaccine delivery due to the fact that they can encapsulate antigens in the liposome's lipid bilayer. Because of the fluorescent labeling, it's convenient to follow liposome uptake by immune cells and calculate how the antigen activated the immune system. What's more, because liposomes can be used with both hydrophilic and hydrophobic antigens, vaccines that can attack any variety of pathogen can be created. As fluorescence imaging is used to observe how the vaccine-loaded liposomes spread and uptake, scientists can learn more about the immune system's response to the vaccine and optimise its composition for efficacy.

Alternate Names:
Fluorescein-Labeled Phosphatidylcholine Liposomes
Fluorescein-Tagged Phosphatidylcholine Liposomes
Fluorescein-PC Liposomes
Non-PEGylated Fluorescein
Fluorescein-Labelled PC Vesicles
Fluorescent Phosphatidylcholine Vesicles
PC Liposomes with Fluorescein Dye

References:
1. Huangying Guo, et al.; Reduction-responsive release property of egg phosphatidylcholine liposomes incorporating benzyl disulfide. Journal of Industrial and Engineering Chemistry. 2016, Volume 44, 25, Pages 105-111.

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