A systemic route for drug loading to lymphatic phagocytes.
Lymph nodes are primary germination and proliferation sites for many types of pathogens. Maintaining therapeutic levels of appropriate chemotherapeutic agents in the lymph node tissue is critical for the treatment of both infection and cancer. This study was intended to develop a systemic route for loading lymph node phagocytes with drugs, using a lymph node specific nanocarrier. The latter is assembled as a 10-15 nm particle with a drug-carrying core and a phagocyte-homing poly(1-->6)-alpha-d-glucose based interface. Biokinetics and microdistribution of the model carrier were investigated in vivo. Nanocarrier accumulation in lymph nodes reached 30-35% dose/g in central lymph nodes, with deposition in various phagocytic cell populations. The latter included cells harboring inhaled microparticles translocated to lymph nodes from the lungs. In view of the nanocarrier ability to transport and release significant amounts of various drug substances, the data suggests feasibility of systemic drug loading to lymphatic phagocytes and, through drug release, to the neighboring cells.
Papisov
M I
MI
Harvard Medical School, Boston, Massachusetts 02114-2696, USA. papisov@helix.mgh.harvard.edu
Yurkovetskiy
A
A
Syed
S
S
Koshkina
N
N
Yin
M
M
Hiller
A
A
Fischman
A J
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005260:Female; D005947:Glucose / Q000031:analogs & derivatives* / Q000378:metabolism*; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism*; D008208:Lymphatic System / Q000378:metabolism; D008297:Male; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D005947:Glucose