In the ever-evolving field of drug delivery, the development of novel and efficient carriers is paramount for enhancing the therapeutic efficacy of drugs while minimizing side effects. One such promising carrier is the FITC-Dextran labeled DOTAP liposome. This innovative drug delivery system combines the benefits of liposomes, well-known for their ability to encapsulate both hydrophilic and hydrophobic drugs, with the cationic lipid DOTAP (dioleoyltrimethylammonium propane), which facilitates cellular uptake. Furthermore, the addition of FITC-Dextran, a fluorescent marker, allows for the tracking and visualization of these liposomes within biological systems, providing invaluable insights into their distribution, accumulation, and overall behavior in vivo. This unique combination holds great potential for targeted drug delivery, particularly in the treatment of cancers and other diseases where precise drug delivery is crucial. Liposomes are spherical vesicles with an aqueous core enclosed by one or more phospholipid bilayers. They have been extensively studied and utilized in drug delivery due to their biocompatibility, biodegradability, and ability to protect encapsulated drugs from degradation. Liposomes can vary in size, charge, and lipid composition, allowing for customization to meet specific therapeutic needs. This versatility makes them suitable for a wide range of applications, from delivering small molecule drugs to large biological molecules such as proteins and nucleic acids. DOTAP, a cationic lipid, is incorporated into the liposome formulation to enhance its interaction with negatively charged cellular membranes, thereby promoting endocytosis and facilitating drug delivery into cells. This feature is particularly advantageous for delivering genetic material such as DNA or RNA, which often requires efficient cellular uptake to achieve therapeutic effects. By incorporating DOTAP, researchers aim to improve the delivery efficiency and therapeutic outcomes of the encapsulated drugs or genetic material. FITC-Dextran serves a dual purpose in this formulation. As a high molecular weight fluorescent marker, FITC-Dextran allows for the real-time tracking of liposome distribution and accumulation in tissues. This is crucial for understanding the biodistribution and pharmacokinetics of the drug delivery system, enabling researchers to optimize the formulation for better targeting and reduced off-target effects. Additionally, FITC-Dextran can be used to assess the integrity of the liposomes and their stability in biological environments. The fluorescent labeling thus provides a powerful tool for both preclinical studies and potential clinical applications, offering a means to monitor and refine the drug delivery process to achieve maximum therapeutic efficacy.
Figure 1. Formation of lipoplexes from unilamellar DOTAP-Cholesterol liposomes. (Heidari Z, et al. 2017)
The incorporation of DOTAP into liposomes not only improves their interaction with cellular membranes but also enhances the transfection efficiency for gene therapy applications. Cationic lipids like DOTAP are known to form complexes with negatively charged nucleic acids, protecting them from enzymatic degradation and facilitating their entry into cells. This is particularly beneficial for the delivery of siRNA, mRNA, and plasmid DNA, which are increasingly being used in therapies for genetic disorders, cancer, and infectious diseases. By enhancing the stability and delivery of these nucleic acids, DOTAP-liposomes can significantly improve the therapeutic outcomes of gene-based treatments.The use of FITC-Dextran labeling provides an additional layer of functionality to DOTAP-liposomes, making them not only effective carriers but also valuable tools for research and development. The fluorescent properties of FITC-Dextran enable the visualization of liposome distribution in real-time using various imaging techniques such as fluorescence microscopy, flow cytometry, and in vivo imaging systems. This capability is essential for studying the pharmacokinetics and biodistribution of the liposomes, helping researchers to understand how the delivery system behaves in different biological environments. Furthermore, it allows for the monitoring of drug release kinetics and the assessment of therapeutic efficacy in preclinical models.
Combining these elements, FITC-Dextran labeled DOTAP liposomes represent a sophisticated approach to drug delivery that leverages the strengths of each component. The liposome structure protects the drug, the DOTAP enhances cellular uptake, and the FITC-Dextran allows for precise tracking and analysis. This multifaceted system holds promise for a wide range of applications, from targeted cancer therapies to the delivery of genetic material for gene therapy. The ability to track and visualize the liposomes in vivo provides invaluable feedback for optimizing their design and improving their performance. As research progresses, these liposomes could offer a more effective and less invasive means of delivering drugs, ultimately improving patient outcomes and advancing the field of targeted drug delivery. The integration of DOTAP and FITC-Dextran into liposome formulations exemplifies the advancements in nanotechnology and materials science aimed at improving drug delivery systems. Nanotechnology has revolutionized the field of medicine by enabling the design of carriers that can navigate the complexities of the human body, protect therapeutic agents from degradation, and release them at specific sites of action. FITC-Dextran labeled DOTAP liposomes are a testament to this progress, combining biocompatibility, enhanced cellular uptake, and real-time tracking capabilities into a single platform. Future research on FITC-Dextran labeled DOTAP liposomes will likely focus on further optimizing their properties for specific therapeutic applications. This could involve fine-tuning the lipid composition to improve stability and reduce potential cytotoxicity, as well as developing methods to control the size and charge of the liposomes for better targeting and cellular uptake. Additionally, researchers may explore the use of different fluorescent markers or imaging techniques to enhance the visualization and tracking of the liposomes in vivo.
Alternate Names:
Dextran-DOTAP Liposomes
DOTAP-Dextran Liposomes
Dextran-coated DOTAP Liposomes
Dextran-Modified DOTAP Liposomes
DOTAP Liposomes with Dextran Labeling
Dextran-Functionalized DOTAP Liposomes
References:
1. Heidari Z, et al. Impact of the Charge Ratio on the In Vivo Immunogenicity of Lipoplexes. Pharm Res. 2017, 34(9):1796-1804.
2. Miranda D, et al. Indocyanine green binds to DOTAP liposomes for enhanced optical properties and tumor photoablation. Biomater Sci. 2019, 7(8):3158-3164
Characterization and in vivo performance of dextran-spermine polyplexes and DOTAP/cholesterol lipoplexes administered locally and systemically
Biomaterials
Authors: Eliyahu H, Joseph A, Schillemans JP, Azzam T, Domb AJ, Barenholz Y.
Abstract
In this study, we compared two systems which can be applied for transfection in vitro and in vivo: polyplexes based on the polymer dextran-spermine (D-SPM) and lipoplexes based on 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol. The carriers differ in (1) solubility in aqueous media, (2) source of the positive charges (quaternary amines for DOTAP and primary plus secondary amines for D-SPM), (3) electrostatics, i.e., for lipid and polymer, respectively: zeta-potential (81.0 and 48.1 mV), surface potential (180 and 92 mV), and surface pH (10.47 and 8.97), and (4) charge distribution (ordered versus non-ordered). The stability of the complex upon interaction with serum proteins was studied by means of fluorescence resonance energy transfer (FRET) between rhodamine-labeled cationic carriers and fluorescein-labeled DNA. Addition of serum increases the lipid-DNA average distance and decreases the polymer-DNA distance. However, FRET efficiency indicates that serum proteins do not induce a major DNA dissociation for either polyplexes or lipoplexes. Comparing the biodistribution of rhodamine-labeled complexes and the transgene expression after intravenous (i.v.), intramuscular (i.m.), and intranasal (i.n.) administration, we found that local administration of lipoplexes resulted in the lipoplexes remaining at the site of injection, whereas the polyplexes showed systemic distribution, accompanied by transgene expression in lungs and liver. It is suggested that the high water-solubility of the polymer combined with its lower positive charge (compared to DOTAP), which makes its association with the cells at the site of injection weaker, enables the polymer to reach and transfect distant organs through the blood stream. Using chemically modified D-SPM, we demonstrated the importance of high density of positive charges and a sufficient level of secondary amines for achieving efficient transgene expression in vivo.
Datasheet