Liposome Encapsulated Drugs

Lipid excipients and surfactants can keep drug molecules in solution before and after administration. Among all technologies for improving bioavailability, lipid drug delivery systems have been most extensively studied as a formulation technology to address solubility and permeability issues. Among them, liposome is a dosage form for drug delivery. It is a spherical-like artificial membrane with phospholipid as the wall material. It self-aggregates in water to form ultra-micro spherical particles with a bilayer structure. It is very close to the plasma membrane structure of human cells and has good physiological compatibility with the human body. Therefore, as a drug-carrying system, liposomes have many advantages such as small human body rejection, targeted drug delivery, long-term sustained release of drugs, improved stability and reduced side effects.

Fig. 1. Lipid-encapsulated drugs (Colloids and Surfaces B: Biointerfaces. 2017, 154: 178-185).

How Liposome Drugs Work?

Liposome drugs work by encapsulating the drug in a lipid bilayer or water core and delivering it to target cells or tissues. Liposomes can protect drugs from degradation and clearance, enhance the solubility and stability of drugs, and reduce the toxic and side effects of drugs. Liposomes can also be modified with ligands or stimulus-responsive compounds to enable active or passive targeting of specific receptors or biomarkers. Liposomes interact with cells in four ways to release their contents: adsorption, endocytosis, lipid exchange, or fusion. The release mechanism depends on the composition, size, charge, and surface properties of the liposomes, as well as the cell type and environment.

• Adsorption occurs when liposomes bind to the cell surface through electrostatic or hydrophobic interactions. This may trigger drug release from the liposome surface or induce cellular signaling pathways.
• Endocytosis occurs when liposomes are internalized by cells via phagocytosis or pinocytosis. This may result in drug release within endosomes or lysosomes, where they can escape into the cytoplasm or remain trapped.
• Lipid exchange occurs when lipids or drugs are transferred from the liposome membrane to the cell membrane or vice versa. This may alter the membrane properties and function of liposomes and cells.
• Fusion occurs when liposomes fuse with cell membranes or intracellular vesicles. This may result in drug delivery directly to the cytoplasm or organelles.

Drug Loaded Liposomes

Since the first anti-tumor liposome that was successfully used clinically - doxorubicin liposome (doxil) - was launched in 1995, many liposome products have been used in different disease treatment fields, mainly including anti-tumor, anti-fungal, analgesic and gene therapy, etc. Based on this, BOC Sciences launched a liposome encapsulation service platform for small molecule drugs.

Liposomal Doxorubicin Formulations

Doxorubicin liposomes consist of the small molecule drug doxorubicin encapsulated in liposomes. The formula helps improve the delivery of doxorubicin to cancer cells, potentially reducing side effects and increasing its effectiveness in treating certain types of cancer. At present, from the perspective of the global market, doxorubicin liposomes have clinical applications in various diseases such as Kaposi's sarcoma, leukemia, breast cancer, multiple myeloma, ovarian cancer, endometrial cancer, liver cancer, osteosarcoma, and kidney cancer. BOC Sciences can provide customized liposome services for doxorubicin and doxorubicin hydrochloride, including lipid composition and liposome size. Our liposome-encapsulated doxorubicin offers high product stability and consistency, tight particle size distribution and high drug entrapment efficiency.

Liposomal Paclitaxel Formulations

The paclitaxel lipid system contains paclitaxel in liposomes, which improves its water solubility. Therefore, allergic reactions to paclitaxel liposomes are rare and have good safety. Mechanistically, paclitaxel liposomes target tumor tissues and lymph nodes through the high permeability and retention effect of solid tumors, exert anti-tumor effects and reduce toxic and side effects. At present, paclitaxel liposomes are easier to penetrate into tumor tissues from blood vessels than ordinary paclitaxel, and have the advantages of passive targeting, enhanced therapeutic effect, and reduced cardiac and renal toxicity. The liposome products provided by BOC Sciences include a variety of universal liposome types to support the development of liposomal paclitaxel drugs with high efficiency, high stability, and high reproducibility.

Liposomal Irinotecan Formulations

Irinotecan is a camptothecin-like compound, a pentacyclic monoterpene alkaloid isolated from the bark and trunk of Camptotheca acuminata. Irinotecan is not pharmacologically active. It is metabolized in the liver by carboxylesterase (such as hCE2) and converted into the active product SN-38, whose activity in inhibiting topoase I is much greater than that of irinotecan. BOC Sciences offers comprehensive services related to liposomal irinotecan formulations. Our liposomal drug encapsulation services are designed to improve the pharmacokinetics and biodistribution of small molecule drugs. Our services include the development, manufacturing and characterization of liposomal irinotecan formulations for preclinical and clinical applications.

Liposomal Topotecan Formulations

Topotecan is a water-soluble plant alkalizer that exerts strong anti-cancer activity mainly by affecting the normal function of topoisomerase I. By encapsulating topotecan in liposomes, the solubility and stability of the drug are improved, allowing for a more controlled and sustained release of the drug in the body. BOC Sciences' liposomal topotecan formulation is designed to overcome the limitations of traditional drugs by improving its solubility, stability and targeted delivery to cancer cells. Our encapsulation services also support customers in developing custom liposome formulations based on specific needs.

Liposomal Clodronate Formulations

Clodronate, a disodium dichloromethylene diphosphate, belongs to the bisphosphonate family. It is an effective clinical drug for the treatment of bone metabolic disorders, such as osteoporosis, arthritis and bone and joint pain. The properties of free disodium clodronate and liposomes are complementary. The clodronate dissolved in the aqueous solution is wrapped into the aqueous phase of the phospholipid bilayer during the preparation of liposomes to form clodronate liposomes. BOC Sciences' clodronate liposome encapsulation services have an experienced team of scientists and regulatory experts who can provide comprehensive support services for the development and commercialization of liposomal clodronate formulations.

Advantages of Liposomal Drugs

There are significant differences between liposome drugs and other complex drug products in terms of structure, composition, and function. Therefore, different methods and standards are also required for characterization, quality control, bioequivalence assessment, and regulatory approval.

• The shape of liposome drugs is regular spherical shape, and the particle size is generally between 50 and 500nm.
• The main components of liposome drugs are phospholipids and cholesterol, which can spontaneously form a bilayer structure in aqueous solution.
• Liposome drugs can encapsulate both hydrophilic and hydrophobic drugs inside, with hydrophilic drugs located in the water core and hydrophobic drugs located in the lipid bilayer, thereby achieving double protection of the drug.
• Liposome drugs can significantly improve the solubility, stability, bioavailability and targeting of drugs, thereby improving the therapeutic effect and safety of drugs.

Drug-loaded Lipid Products

In addition to liposome encapsulation of small molecule drugs, we also support the encapsulation of a variety of bioactive molecules, including nucleic acids, proteins, peptides, and vaccines. For specific service details, please refer to liposome encapsulation services. In addition, we have comprehensive technologies to support lipid analysis and characterization, such as particle size analysis, zeta potential measurement, drug encapsulation efficiency determination, drug release kinetic studies, and stability testing under various storage conditions.

Reference

1. Sapra, M. et al. Engineering of layered, lipid-encapsulated drug nanoparticles through spray-drying. Colloids and Surfaces B: Biointerfaces. 2017, 154: 178-185.