Nanoparticle migration and delivery of Paclitaxel to regional lymph nodes in a large animal model.
BACKGROUND
The aim of this study was to demonstrate feasibility of migration and in situ chemotherapy delivery to regional lymph nodes (LN) in a large animal model using an expansile polymer nanoparticle (eNP) delivery system.


METHODS
Dual-labeled 50-nm and 100-nm eNP were prepared by encapsulating an IR-813 near-infrared (NIR) fluorescent dye within coumarin-conjugated expansile polymer nanoparticles (NIR-C-eNP). NIR imaging and fluorescent microscopy were used to identify intralymphatic migration of NIR-nanoparticles to draining inguinal or mesenteric LN after injection in swine hind legs or intestine. Nanoparticle-mediated intranodal delivery of chemotherapy was subsequently assessed with Oregon Green paclitaxel-loaded NIR-eNP (NIR-OGpax-eNP).


RESULTS
NIR imaging demonstrated direct lymphatic migration of 50-nm, but not 100-nm, NIR-C-eNP and NIR-OGpax-eNP to the draining regional LNs after intradermal injection in the hind leg or subserosal injection in intestine. Fluorescent microscopy demonstrated that IR-813 used for NIR real-time trafficking colocalized with both the coumarin-labeled polymer and paclitaxel chemotherapy and was identified within the subcapsular spaces of the draining LNs. These studies verify nodal migration of both nanoparticle and encapsulated payload, and confirm the feasibility of focusing chemotherapy delivery directly to regional nodes.


CONCLUSIONS
Regionally-targeted intranodal chemotherapy can be delivered to draining LNs for both skin and solid organs using 50-nm paclitaxel-loaded eNP.
Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Onkar V
OV
Khullar
Aaron P
AP
Griset
Summer L
SL
Gibbs-Strauss
Lucian R
LR
Chirieac
Kimberly A V
KA
Zubris
John V
JV
Frangioni
Mark W
MW
Grinstaff
Yolonda L
YL
Colson
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage*; D011108:Polymers; D019265:Spectroscopy, Near-Infrared; D013552:Swine
D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D017239:Paclitaxel