title: Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and cytotoxicity in colon cancer cells: In vitro and in vivo study.
abstract: In present investigation, initially curcumin was complexed with 2-HP-β-CD (curcumin-2-HP-β-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-β-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-β-CD cavity with apparent stability constant of 3.35×10-3M. Furthermore, the mean particle size of 6.8±2.6μm and +39.2±4.1mV surface charge of curcumin-2-HP-β-CD-complex-CMs in addition to encapsulation efficiency of about 79.8±6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-β-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH ∼7.0-8.0, almond emulsion-β-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-β-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by ∼8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-β-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer.
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Jyoti
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India.
authors.forename: Richa Kaur
authors.initials: RK
authors.lastname: Bhatia
authors.affiliation: Molecular Simulation Group, Department of Pharmaceutical Chemistry, Bombay College of Pharmacy Mumbai, India.
authors.forename: Elvis A F
authors.initials: EAF
authors.lastname: Martis
authors.affiliation: Molecular Simulation Group, Department of Pharmaceutical Chemistry, Bombay College of Pharmacy Mumbai, India.
authors.forename: Evans C
authors.initials: EC
authors.lastname: Coutinho
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India.
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Jain
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chandra
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab 140307, India. Electronic address: jitenderpharmacy@gmail.com.
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D019540:Area Under Curve; D048271:Chitosan / Q000737:chemistry*; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D056004:Molecular Dynamics Simulation; D010316:Particle Size; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D048271:Chitosan; D003474:Curcumin
keywords: 2-HP-β-CD; Chitosan microspheres; Colon cancer cell; Curcumin; Inclusion complex