Intramuscular injection (IM) is installing medications into the depth of specifically selected muscles. The bulky muscles have good vascularity, and therefore the injected drug quickly reaches the systemic circulation and thereafter into the specific region of action, bypassing the first-pass metabolism. It is one of the most common medical procedures to be performed annually. 

In intramuscular (IM) injections, the medication is deposited deep into the muscle mass, past the dermis and subcutaneous tissue, and into the very deepest layers of the muscle, where the rich blood supply allows for rapid and full absorption. The muscles also contain large blood vessels and nerves, so it is important to place the needle correctly to avoid damage to these structures. There are five recommended sites for intramuscular injections: Dorsogluteal, Ventrogluteal, Deltoid, Vastus lateralis and Rectus femoris.

Generally, we would prefer the intramuscular (IM) route to delivery drugs when we meet the following cases:

1. We desire a longer effect time than intravenous (IV) injection.
2. Delivering drugs cannot be given via subcutaneous (SC) route due to high irritation.
3. Delivering drugs cannot be given intravenously due to the presence in oily solutions. Drugs that are water-soluble can be absorbed quickly from IM sites while drugs that are oil-soluble take more time (up to weeks after injection) to be absorbed.

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