Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma.
Here we describe the O-carboxymethyl chitosan nanoparticles (CMCNP) modified by glycyrrhizin (GL) with various substitution degrees as hepatocellular carcinoma (HCC)-targeted delivery vehicles, which could efficiently deliver paclitaxel (PTX) into HCC. The resultant CMCNP-GL exhibited spherical in shape and high stability in plasma with fixed negative charged (~-30 mV) and a size range of 100-205 nm. PTX was loaded into CMCNP-GL with a maximal encapsulation efficiency of 83.7% and performed a biphasic release. CMCNP-GL promoted liver cancer SMMC-7721 cell internalization by approximate 10.0-fold as compared to unmodified CMCNP. Within 72 h, the IC(50) of PTX/CMCNP-GL, PTX/CMCNP, and PTX injection was 2.7-3.2, 8.1, and 13.5 μg/mL, respectively. Biodistribution experiments revealed that PTX/CMCNP-GL exerted significantly superior targeting to tumor than PTX/CMCNP. The in vivo tumor inhibition ratio of PTX/CMCNP-GL was 87.5%, showing remarkably higher than that of PTX/CMCNP (64.0%) and PTX injection (34.5%). CMCNP-GL with different substitution degrees possessed similar targeting property and therapeutic efficacy. Furthermore, toxicity studies suggested that blank CMCNP-GL had no systemic or hepatic toxicity.
State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China.
Lili
L
Shi
Cui
C
Tang
Chunhua
C
Yin
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D019695:Glycyrrhizic Acid / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D010316:Particle Size; D012235:Rhodamines / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D004337:Drug Carriers; C504164:O-carboxymethylchitosan; D012235:Rhodamines; D019695:Glycyrrhizic Acid; D048271:Chitosan; C029773:rhodamine B; D017239:Paclitaxel