Targeting liver cancer via ASGP receptor using 5-FU-loaded surface-modified PLGA nanoparticles.
BACKGROUND
Liver cancer is widespread liver malignancy in the world, for an estimated one million deaths annually.


OBJECTIVE
In present work, lactobionic acid conjugated PLGA nanoparticles (LDNPs) bearing 5-Fluorouracil (5-FU) were developed for targeted delivery to hepatocellular carcinoma.


METHODS
Lactobionic acid conjugated PLGA was used to prepare LDNPs using modified emulsion diffusion method.


RESULTS
They were characterised for particle morphology, particle size (below 150 nm), zeta potential and polydispersity index (PDI ∼0.35), entrapment efficiency (∼60.23%), and cumulative percent drug release.


CONCLUSIONS
LDNPs in ex-vivo cell line studies on human cancer cell line HepG2 exhibited significantly higher cytotoxicity compared to 5-FU and DNPs (unconjugated PLGA NPs) with growth inhibition 50% (GI50) of 66.7 µg/mL, 50.2 µg/mL and 35.5 µg/mL, respectively. In vivo studies exhibited higher drug concentration about 37.52 ± 0.68% in liver as compared to other organs and plasma.


CONCLUSIONS
Thus, LDNPs showed high drug loading, specificity, biocompatibility and efficacy in treatment of liver cancer.
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University , Sagar, Madhya Pradesh , India.
Ruchi
R
Dangi
Pooja
P
Hurkat
Ankit
A
Jain
Satish
S
Shilpi
Ashish
A
Jain
Arvind
A
Gulbake
Sanjay K
SK
Jain
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000964:Antimetabolites, Antineoplastic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005472:Fluorouracil
5-FU; ASGP; HePG2; PLGA; liver cancer