Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles

Abstract

The lymphatic system plays a crucial role in the immune system's recognition and response to disease, and most solid cancers initially spread from the primary site via the tumor's surrounding lymphatics before hematological dissemination. Hence, the lymphatic system is an important target for developing new vaccines, cancer treatments, and diagnostic agents. Targeting the lymphatic system by subcutaneous, intestinal, and pulmonary routes has been evaluated and subsequently utilized to improve lymphatic penetration and retention of drug molecules, reduce drug-related systemic toxicities, and enhance bioavailability of poorly soluble and unstable drugs. Lymphatic imaging is an essential tool for the detection and staging of cancer. New nano-based technologies offer improved detection and characterization of the nodal diseases, while new delivery devices can better target and confine treatments to tumors within the nodal space while sparing healthy tissues. This manuscript reviews recent advances in the field of lymphatic drug delivery and imaging and focuses specifically on the development of liposomes and solid lipid nanoparticles for lymphatic introduction via the subcutaneous, intestinal, and pulmonary routes.

Figure 1

Thoracic images in posterior view obtained after ⁹⁹mTc-Liposome aerosol inhalation, in the pig n° 18. a) 5 min after the inhalation – visualization of hilar draining chains; b) 10 min after the inhalation – individualization of hilar draining chains; c) 13 min after the inhalation – transdiaphragmatic drainage; d) 30 min after the inhalation – initial visualization of the aortic chain ganglia (Adapted from [8]).

Fig 2

Gamma camera images of the lower portion of rabbits following subcutaneous injection (0.3 ml) of various [99mTc] liposomes in each hind foot at either 30 minutes, 60 minutes or 24 hours post injection. The images show the injection site in the hind feet, the popliteal node region and iliac node region. (C) 124 nm PEG-liposomes (both feet); (D) 124 nm Negative-liposomes (both feet).