Pharmacokinetics and biodistribution of negatively charged pectin nanoparticles encapsulating paclitaxel.

Pectin, a naturally occurring biopolymer has been found to have increasing applications in the pharmaceutical and biotechnology industry. Sugars with their three-dimensional structures are important for many biological functions. We report preparation of negatively charged pectin nanoparticles encapsulating paclitaxel, a broad-spectrum anticancer drug for possible therapeutic applications. The mean diameter of the nanoparticles was ~300-350 nm with an encapsulation efficiency ~17 %. The TEM studies indicated that the particles were spherical in shape and their sizes are in unison with the DLS size spectra. The surface charge of pectin polymer was -5 mV and of nanoparticles were ~ -32 mV. The enhanced surface charge shows greater stability. The high electrophoretic mobility of ~3.5 to 1.5 μmcm/Vs confirmed the nano-size of particles. We compared the cytotoxic effect of paclitaxel (Pax) per se, pectin nanoparticles (PPN), and pectin chains on Hep G2, hepatic carcinoma cell line. Dose-dependent cytotoxicity was observed, wherein ~21.7 ± 3.2 % cytotoxicity was observed by PPN, but Pax per se showed ~55.6 ± 3.5 % cytotoxicity in a 72-h assay. The pharmacokinetics and biodistribution studies on Balb/c mice indicated that the nanoparticles had prolonged plasma retention of the drug with major accumulation in liver tissue after an i.v. tail vein injection of 20 mg/kg drug. The rank order of concentration are as follows, i.e., liver > kidney > lung > spleen for the PPN and spleen > liver > kidney ≥ lung for Pax per se. The in vitro studies clearly indicated that the efficacy of the drug was not compromised by encapsulation, making it a good candidate to deliver biopharmaceuticals. Nanoparticles produced free radicals in the free cell system and this ability caused oxidative stress, which may give rise to inflammation, cell destruction, and genotoxicity. Thus, the results obtained in this study holds great promise for pectin nanoparticles to be exploited for passive delivery of paclitaxel to tumor tissues, in particular, liver cancers.