Overcoming physiological barriers by nanoparticles for intravenous drug delivery to the lymph nodes

Abstract

The lymph nodes are major sites of cancer metastasis and immune activity, and thus represent important clinical targets. Although not as well-studied compared to subcutaneous administration, intravenous drug delivery is advantageous for lymph node delivery as it is commonly practiced in the clinic and has the potential to deliver therapeutics systemically to all lymph nodes. However, rapid clearance by the mononuclear phagocyte system, tight junctions of the blood vascular endothelium, and the collagenous matrix of the interstitium can limit the efficiency of lymph node drug delivery, which has prompted research into the design of nanoparticle-based drug delivery systems. In this mini review, we describe the physiological and biological barriers to lymph node targeting, how they inform nanoparticle design, and discuss the future outlook of lymph node targeting.

Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons

“…Conventional administration of therapeutic molecules via intravenous or interstitial injection failed to attain therapeutic level unless using a highly toxic dose. This is attributed to the rapid washing of therapeutic molecules from interstitial space via rapid blood flow (Trac and Chung 2021 ). Therefore, therapeutic molecules are usually loaded within nanosystems to enhance LDD where their particle size plays a crucial role in LDD (Punjabi et al 2021 ).…”

Biomimetic nanoparticles directly remodel immunosuppressive microenvironment for boosting glioblastoma immunotherapy

“…As previously reported, the immunosuppressive effects could be reduced by 1-methyl- d -tryptophan (also known as indoximod, IND) [ 24 ], which has been used in the clinical trials with a high dose due to the lack of targeting capability and the low accumulation in tumor [ 25 ]. To increase the therapeutic efficacy and reduce the potential side effects of IND, nanoparticles were used as carriers to deliver IND for increasing its accumulation in tumor through the passive targeting effect of nanoparticles [ 26 ].…”

A core-satellite micellar system against primary tumors and their lymphatic metastasis through modulation of fatty acid metabolism blockade and tumor-associated macrophages

“…8 Although chemotherapy is the main strategy for solid tumor treatment, it exhibits limited efficacy towards lymphatic metastasis. Complex biological barriers hinder lymphatic drug delivery [9][10][11] and chemotherapy drugs would inevitably affect normal cells in LNs. Therefore, a milder and more effective lymphatic metastasis therapeutic strategy needs to be urgently developed.…”