Polymer-Modified Liposomes Synthesis Service

What is Polymer-Modified Liposome?

Polymer modification of liposomes represents a sophisticated approach to enhancing drug delivery systems. By improving colloidal stability, prolonging circulation times through evasion of the mononuclear phagocytic system, and enabling controlled release of encapsulated drugs, polymer-modified liposomes offer a versatile platform for targeted and responsive drug delivery. Additionally, their ability to precisely target diseased cells or tissues and respond to external stimuli further amplifies their therapeutic potential. Collectively, these advancements improve pharmacokinetic properties, biodistribution, toxicity profiles, and overall therapeutic efficacy, positioning polymer-modified liposomes as highly promising candidates for addressing diverse medical challenges, particularly in oncology and beyond.

BOC Sciences' Polymer-Modified Liposome Synthesis Services

BOC Sciences offers Polymer-Modified Liposome Synthesis Services, utilizing advanced research in polymer surface modification to finely adjust the physicochemical properties of liposomes. Special attention is given to modulating their interfacial properties to alter related interactions, such as liposome-liposome and liposome-serum protein interactions. Multifunctional polymers, including natural and synthetic variants, have long been renowned as customizable drug delivery vehicles due to their tailored structures, properties, and functionalities. Customized polymer-modified liposomes demonstrate exceptional performance, enhancing colloidal stability, extending circulation time, and promoting targeting and triggered release based on the characteristics of the embedded polymers. Our tailored Polymer-Modified Liposome services are primarily based on strategies including grafting polymers onto the liposome surface or physically adsorbing polymer coatings onto liposomes. Additionally, by introducing polymers with various specific functionalities, multifunctional liposomes can be designed and prepared. Our team of experienced scientists specializes in the design and synthesis of polymer-coated liposomes tailored to meet the unique requirements of our clients. With state-of-the-art facilities and cutting-edge technologies, we deliver high-quality liposomal formulations with precise control over particle size, polymer composition, and drug loading capacity.

BOC Sciences' Polymer Modification Methods

The outer surface of liposomes permits the adsorption of polymers by non-specific (electrostatic, dipolar charge, hydrogen bonding, van der Waals) interactions. As a result of the adsorbed polymers, the interfacial and physicochemical properties of the liposomes are altered, resulting in colloidal, biological, and mechanical stability, prolonged cyclic half-life, reduced permeability and controlled release of payloads, and targeting. Direct adsorption of single-component hydrophilic polymers onto the liposome surface, doping of multiple hydrophobic anchor-modified polymers (comb structures) into lipid bilayers, layer-by-layer (LbL) deposition of complementary polymers, and cross-linking of polymers by caged liposomes are some of the most commonly used methods.

Monolayer Polymer Adsorption

Polymer-coated liposomes are achieved by adding polymer solution dropwise into pre-prepared liposome dispersion, avoiding pre-functionalization of the polymers, which is a feasible way of modifying the properties of liposomes. The chemical structure, charge, and molecular weight of polymers predominantly determine their interaction with liposomes and the polymer-liposome configuration. Polymers can adsorb onto liposomes with opposite charges through electrostatic, hydrophobic, and hydrogen bonding interactions, and can bind to zwitterionic PC vesicles, introducing charges to the surface. Therefore, liposomes modified with charged polymers are electrostatically repulsive and are considered to be colloidally stable. The coating layer also serves as a barrier controlling the release rate of encapsulated drugs.

Layer-by-Layer Deposition (LbL)

LbL coating is a simple process achieved by subsequent adsorption materials to form a stable layer on the substrate/surface. Electrostatic attraction is the most commonly used driving force fabricating LbL structures. Other assemblies by virtue of hydrophobic, charge-transfer, host-guest, biologically specific, coordination chemistry, and covalent bonding interactions have also been reported. The versatility of LbL assembly, particularly of the outermost layer, provides a wide range of properties and functions to the drug delivery systems, including steric stability, stealth properties, active targeting, and environmental responsiveness. Compared to liposomes coated with a single layer of polymer, thin multilayered polymers are more robust and have greatly increased stability against damage in biological environments as well as surfactants, lyophilization, and spray drying.

Polymer Caging

Polymer caging is the immobilization of polymers modified on the surface of liposomes by chemical cross-linking to form a stable polymer cage layer. This method enhances the stability and mechanical strength of the liposome, prevents polymer detachment and release, and improves the stability of the liposome in the biological environment and the controlled release of the drug. Precise regulation of drug release can also be achieved by introducing pH-sensitive or enzyme-sensitive cross-linking structures, thus realizing drug release and targeted delivery under specific conditions.

Types of Polymers Modifications from BOC Sciences

Natural Polymers

such as hyaluronic acid (HA), chitosan, alginate, etc., are biocompatible and biodegradable and are commonly used to improve the stability and targeting of liposomes.

Synthetic Polymers

Such as polyvinyl alcohol (PVA), amphiphilic polymers, dendrimers, etc., with diverse structures and properties, can be used to enhance the performance and function of liposomes.

Stimulus-response Polymer

Triggering the release of the encapsulated therapeutic agent at the desired site is important to achieve high bioavailability and therapeutic efficacy. Drug delivery liposomes that respond to one or more stimuli (e.g., pH, temperature, light, redox, and specific enzymes) can be used to achieve effective controlled release and enhance the therapeutic efficacy of the payload. For Example, pH-responsive polymers are as fellows:

• Poly(aspartic acid) modified with carboxyl groups and grafted with hydrophobic anchor octylamine (PASP-g-C8)
• pH-sensitive PEG-lipid conjugates, such as DSPE-PEG-H7K(R2)2/TH/STP and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-PSDM)
• Hyaluronic acid (HA) derivatives bearing 3-methyl glutarylated (MGlu) units or 2-carboxycyclohexane-1-carboxylated (CHex) units (MGlu-HA or CHex-HA)
• 3-methylglutarylated hyperbranched poly(glycidol) (MGlu-HPG)
• Other copolymers with weakly charged groups and hydrophobic groups

* More customized polymer-modified liposome services are still being updated. For more tailored polymer modified liposome needs, please feel free to contact us.

Advantages of BOC Sciences' Polymer-Modified Liposome

• Improved Stability: The presence of polymers on the liposome surface enhances colloidal, biological, and mechanical stability. This stability prevents aggregation, fusion, and deformation of liposomes, ensuring their integrity during storage and administration.
• Prolonged Circulation Half-life: Coating liposomes with polymers prolongs their circulation half-life in the bloodstream. This extended circulation time increases the chances of liposomes reaching target tissues or cells, enhancing therapeutic efficacy.
• Controlled Release: Polymers on the liposome surface act as a barrier, controlling the release rate of encapsulated drugs. This controlled release ensures sustained and prolonged delivery of therapeutics, leading to optimized drug concentrations at the target site and reducing systemic toxicity.
• Reduced Permeability: Polymer-coated liposomes exhibit reduced permeability, preventing premature leakage of encapsulated agents. This feature enhances the stability of liposomal formulations and ensures the integrity of the payload until reaching the desired site of action.
• Targeting Abilities: Certain polymers, such as hyaluronic acid (HA), possess inherent targeting capabilities. By modifying liposomes with targeting ligands or derivatives of these polymers, polymer-coated liposomes can actively target specific cells or tissues, improving therapeutic precision and reducing off-target effects.
• Versatility in Modification: Polymer-coated liposomes offer versatility in modification approaches, including direct adsorption of polymers, incorporation of polymer-modified anchors into the lipid bilayer, layer-by-layer deposition of complementary polymers, and cross-linking of polymers. This versatility allows for fine-tuning of liposomal properties to meet specific therapeutic needs.
• Biocompatibility and Biodegradability: Many polymers used for liposome modification, such as HA, chitosan, and alginate, are biocompatible and biodegradable. These properties ensure minimal adverse effects and facilitate the safe clearance of liposomal formulations from the body.

Case Study

Case Study 1 pH-Sensitive Liposomes Enhance Antigen Delivery for Cancer Immunotherapy

Figure 1. Design of liposome vaccines with pH sensitive activity and immune activation. (Eiji, Y. B, 2016)

A research group aims to utilize pH-sensitive polymer-modified liposomes as effective antigen delivery systems for cancer immunotherapy. Their approach involves loading antigens into liposomes modified with pH-sensitive polymers, as well as adjuvant molecules/systems such as Toll-like receptor (TLR) ligands, cationic lipids, or cytokine (IFN-γ) gene delivery systems. It was shown that dendritic cells (DCs) exhibit efficient cytoplasmic delivery of antigens when treated with pH-sensitive liposomes loaded with antigens (e.g., FITC-labeled ovalbumin), with green fluorescence indicating the presence of FITC-labeled antigens. In addition, red fluorescence indicated the location of liposomes. The findings highlight the potential of such delivery systems to induce protective immune responses against pathogens and therapeutic interventions in hormonal models, underscoring their importance in advancing cancer treatment modalities.

Case Study 2 Hyaluronic Acid-Based pH-Sensitive Liposomes for Targeted Intracellular Drug Delivery in Cancer Chemotherapy

In this study, hyaluronic acid (HA)-based pH-sensitive polymers were engineered for pH sensitivity and targeting properties against cells expressing CD44, a recognized cancer cell surface marker. Two types of HA derivatives, MGlu-HA and CHex-HA, were synthesized using various diacid anhydrides with introduced carboxyl groups, with CHex-HA exhibiting a more hydrophobic side chain structure. The polymer-modified liposomes remained stable at neutral pH but exhibited content release under weakly acidic conditions. Compared to HA-modified or MGlu-HA-modified liposomes or unmodified liposomes, CHex-HA-modified liposomes exhibited enhanced delivery of their contents into CD44-expressing cells. In contrast, these liposomes exhibited minimal uptake by cells expressing lower levels of CD44 protein. Competition assays using free HA or other polymers suggested that HA derivative-modified liposomes may be specifically recognized by CD44. This study highlights the utility of HA derivative-modified liposomes as a targeted intracellular drug delivery system, offering promise for improving the efficacy of cancer chemotherapy while minimizing off-target effects.

FAQ

1: What is the formulation of a liposome?

Structurally, liposomes are spherical or multilayered spherical vesicles self-assembled from diacyl chain phospholipids (lipid bilayers) in aqueous solution. The bilayer phospholipid membrane has a hydrophobic tail and a hydrophilic head, resulting in an amphiphilic structure.

2: What are the polymers used in drug delivery system?

Polymers used in drug delivery systems include biodegradable ones like poly(lactic-co-glycolic acid) (PLGA) and chitosan, as well as biocompatible polymers like polyethylene glycol (PEG). Other examples are polyethyleneimine (PEI) for gene delivery, hydroxypropyl methylcellulose (HPMC) for oral drug delivery, and thermoresponsive polymers like poly(N-isopropylacrylamide) (PNIPAAm). Additionally, hyaluronic acid (HA) is employed for targeted drug delivery, while poly(beta-amino esters) (PBAEs) are utilized for efficient gene delivery.

3: What is the role of polymers in modified drug delivery system?

Polymers have played an integral role in the advancement of drug delivery technology, providing controlled release of therapeutic drugs at constant doses over long periods of time, circulating doses, and adjustable release of hydrophilic and hydrophobic drugs.

Reference

1. Eiji, Y. B. Design of pH-Sensitive Polymer-Modified Liposomes for Antigen Delivery and Their Application in Cancer Immunotherapy. Polymer Journal. 2016, 48: 761–771.