Subcutaneous administration(SC) is done by injecting drugs into the fatty tissues just beneath the skin, which is the standard route of administration in diseases such as diabetes and rheumatoid arthritis. The liposome drug is injected into the fatty subcutaneous tissue situated right under the skin, allowing for the controlled release of the drug over time. The liposome-encased drug molecules are then absorbed by the capillaries or lymphatic vessels in the subcutaneous tissue. With capillary absorption, the liposome enters the bloodstream to be delivered throughout the body. In the case of lymphatic absorption, the liposomes mainly target the immune cells, which are abundant in the lymphatic system. Upon reaching their target site, the liposomes release their drug cargo into cells through a process called endocytosis or by fusion with the cell membrane. Once inside the cells, the drug interacts with its specific intracellular targets, leading to its pharmacological effect in various therapeutic applications. For clodronatelipsomes, the release of clodronate from lysosomes leads to the apoptosis of phagocytic cells.

Applications of Subcutaneous Administration of Liposomes

The application of subcutaneous administration of liposomes is broad-ranging. In cancer therapy, liposomal drug delivery helps reduce the side-effects of conventional chemotherapy, improving patient compliance due in part to the enhanced targeted delivery. It also circumvents drug resistance, which is a major challenge in cancer therapeutics. Liposomes administered subcutaneously can also be used in dermatology for the localized treatment of skin diseases such as skin cancers, psoriasis, eczema, or other dermatological disorders. Furthermore, liposomes are used for the subcutaneous delivery of antigens or adjuvants, thus playing a crucial role in immunotherapy and vaccinology. By encapsulating bioactive compounds, they improve their stability and biological activity, enhancing therapeutic efficacy.

Benefits of Subcutaneous Administration of Liposomes

The method of subcutaneous administration of liposomes provides several benefits. First, it enhances therapeutic efficacy by directing the drug payload to the intended target and protecting them from nonspecific uptake and degradation. This results in reduced systemic toxicity by lowering the exposure of non-targeted organs, thus improving safety profiles of drugs. Additionally, liposomes enable controlled drug release, meaning that medication can be released gradually over an extended duration, potentially reducing the frequency of dosing. Lastly, liposomes provide a solution for the administration of poorly soluble drugs and biologics, carrying these substances effectively into the systemic circulation.

The subcutaneous administration of liposomes offers revolutionary possibilities in overcoming the limitations of traditional drug delivery techniques. As the scientific understanding of these nanocarriers grows, their application will surely continue to evolve, presenting new and exciting opportunities for the world of medicine.

Why Administration Route Matters in Liposomal Delivery

The choice of administration route plays a pivotal role in determining how liposomes behave in biological systems. Factors such as tissue penetration, macrophage uptake, release kinetics, and immune response are significantly impacted by how and where liposomes are introduced. Whether the goal is targeted depletion of specific cell populations, localized drug delivery, or systemic circulation, selecting the appropriate route is essential to achieving optimal experimental or therapeutic outcomes.

Different administration methods can be designed to:

• Maximize site-specific accumulation of liposomes

• Minimize systemic toxicity

• Improve cellular uptake and retention

• Extend circulation half-life

• Facilitate passage across biological barriers (e.g., blood-brain barrier, mucosal membranes)

Key Considerations for Route Selection

Each administration route offers distinct advantages and limitations based on the biological target, therapeutic goals, and the nature of the encapsulated agent (e.g., clodronate, RNA, proteins). Some routes are ideal for localized depletion of macrophages, while others are preferred for systemic effects or mucosal immunity studies. Considerations include:

• Target tissue or organ system

• Desired duration of action

• Accessibility of the administration site

• Volume and formulation characteristics

• Species-specific anatomical factors