Effective drug delivery, in vitro and in vivo, by carbon-based nanovectors noncovalently loaded with unmodified Paclitaxel.
Many new drugs have low aqueous solubility and high therapeutic efficacy. Paclitaxel (PTX) is a classic example of this type of compound. Here we show that extremely small (<40 nm) hydrophilic carbon clusters (HCCs) that are PEGylated (PEG-HCCs) are effective drug delivery vehicles when simply mixed with paclitaxel. This formulation of PTX sequestered in PEG-HCCs (PTX/PEG-HCCs) is stable for at least 20 weeks. The PTX/PEG-HCCs formulation was as effective as PTX in a clinical formulation in reducing tumor volumes in an orthotopic murine model of oral squamous cell carcinoma. Preliminary toxicity and biodistribution studies suggest that the PEG-HCCs are not acutely toxic and, like many other nanomaterials, are primarily accumulated in the liver and spleen. This work demonstrates that carbon nanomaterials are effective drug delivery vehicles in vivo when noncovalently loaded with an unmodified drug.
Berlin
Jacob M
JM
Department of Chemistry, Rice University, MS-222, 6100 Main Street, Houston, Texas 77005, USA.
Leonard
Ashley D
AD
Pham
Tam T
TT
Sano
Daisuke
D
Marcano
Daniela C
DC
Yan
Shayou
S
Fiorentino
Stefania
S
Milas
Zvonimir L
ZL
Kosynkin
Dmitry V
DV
Price
B Katherine
BK
Lucente-Schultz
Rebecca M
RM
Wen
Xiaoxia
X
Raso
M Gabriela
MG
Craig
Suzanne L
SL
Tran
Hai T
HT
Myers
Jeffrey N
JN
Tour
James M
JM
D000818:Animals; D002244:Carbon / Q000737:chemistry*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D004355:Drug Stability; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
D004337:Drug Carriers; D011092:Polyethylene Glycols; D002244:Carbon; D017239:Paclitaxel