title: Long-circulating poly(ethylene glycol)-grafted gelatin nanoparticles customized for intracellular delivery of noscapine: preparation, in-vitro characterization, structure elucidation, pharmacokinetics, and cytotoxicity analyses.
abstract: Noscapine, the tubulin-binding anticancer agent, when administered orally, requires high ED(50) (300-600 mg/kg), whereas intravenous administration (10 mg/kg) results in rapid elimination of the drug with a half-life of 0.39 h. Hence, the development of long-circulating injectable nanoparticles can be an interesting option for designing a viable formulation of noscapine for anticancer activity. Noscapine-enveloped gelatin nanoparticles and poly(ethylene glycol)-grafted gelatin nanoparticles were constructed and characterized. Data indicate that smooth and spherical shaped nanoparticles of 127 ± 15 nm were engineered with maximum entrapment efficiency of 65.32 ± 3.81%. Circular dichroism confirms that nanocoacervates retained the α-helical content of gelatin in ethanol whereas acetone favored the formation of a random coil. Moreover, the Fourier transform infrared and powder X-ray diffraction pattern prevents any significant change in the noscapine-loaded gelatin nanoparticles in comparison with individual components. In-vitro release kinetic data suggest a first-order release of noscapine (85.1%) from gelatin nanoparticles with a release rate constant of 7.611×10(-3). It is to be noted that there is a 1.43-fold increase in the area under the curve up to the last sampling point for the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles over the noscapine-loaded gelatin nanoparticles and a 13.09-fold increase over noscapine. Cytotoxicity analysis of the MCF-7 cell line indicated that the IC(50) value of the noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles was equivalent to 20.8 μmol/l, which was significantly (P<0.05) lower than the IC(50) value of the noscapine-loaded gelatin nanoparticles (26.3 μmol/l) and noscapine (40.5 μmol/l).Noscapine-loaded poly(ethylene glycol)-grafted gelatin nanoparticles can be developed as a promising therapeutic agent for the management of breast cancer.
authors.affiliation: Dr B.R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi.
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
authors.forename: Neerupma
authors.initials: N
authors.lastname: Dhiman
authors.forename: Satish
authors.initials: S
authors.lastname: Sardana
authors.forename: Ritu
authors.initials: R
authors.lastname: Aneja
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chandra
authors.forename: Anju
authors.initials: A
authors.lastname: Katyal
mesh_terms: D000588:Amines / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D004563:Electrochemistry; D005079:Excipients; D005260:Female; D005780:Gelatin; D006801:Humans; D051379:Mice; D018625:Microscopy, Atomic Force; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D009665:Noscapine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D011092:Polyethylene Glycols; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000588:Amines; D020533:Angiogenesis Inhibitors; D005079:Excipients; D011092:Polyethylene Glycols; D009665:Noscapine; D005780:Gelatin