title: Folic acid conjugated guar gum nanoparticles for targeting methotrexate to colon cancer.
abstract: It was envisaged to develop surface modified Guar Gum Nanoparticles (GGNP) with Folic acid (FA) charged with methotrexate (MTX) to target the colon specifically. The MTX loaded FA functionalized GGNP (MTX-FA-GGNP) have been prepared by emulsion crosslinking method. These surface modified nanoparticles were compared with unmodified MTX loaded GGNP (MTX-GGNP). The developed formulations were evaluated for size and size distribution, zeta potential, Differential Scanning Calorimetry (DSC), release profile and uptake studies. The nanoparticles have been found to have average size of 325 nm in diameter having polydispersity index (PDI) 0.177 indicating mono-disperse particles. The zeta potential of the particles was found to be -36.9 mV. The percent growth inhibition of Caco 2 cells with MTX-FA-GGNP was found to be better than MTX-GGNP indicating folate receptor mediated uptake. The MTX-GGNP protects the release of MTX in upper gastrointestinal tract while maximum release of MTX occurred in simulated colonic fluids of pH 6.8. The in vivo uptake studies revealed preferential uptake of nanoparticles formulation in the colon. These studies provide evidences that MTX-FA-GGNP holds promise to address colorectal cancer over-expressing folate receptors. This prototype formulation enjoys dual advantage of having propensity to release the drug in the colon and in the conditions of colorectal carcinoma; it could be better localized and targeted with improved therapy due to over-expression of folate receptors.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226001, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.forename: Ritu
authors.initials: R
authors.lastname: Malik
authors.forename: Ashwni
authors.initials: A
authors.lastname: Verma
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dwivedi
authors.forename: Gabbar Singh
authors.initials: GS
authors.lastname: Banoth
authors.forename: Nagendra
authors.initials: N
authors.lastname: Pandey
authors.forename: Jayant
authors.initials: J
authors.lastname: Sarkar
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003432:Cross-Linking Reagents / Q000737:chemistry; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005685:Galactans / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008351:Mannans / Q000737:chemistry*; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D053149:Plant Gums / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity
chemical_list: D003432:Cross-Linking Reagents; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D005492:Folic Acid; C007894:guar gum; D008727:Methotrexate