title: Development and optimization of curcumin-loaded mannosylated chitosan nanoparticles using response surface methodology in the treatment of visceral leishmaniasis.
abstract: OBJECTIVE
  The study aims at formulation and optimization of macrophage-targeted curcumin-loaded mannosylated chitosan nanoparticles (Cur-MCNPs) of curcumin (CUR) to improve its therapeutic potential in the treatment of visceral leishmaniasis (VL).
  
  
  METHODS
  Response surface methodology (RSM) using central composite design was employed to study the effect of formulation factors on physicochemical-dependent characteristics. Chitosan was coupled with d-mannose, by reductive amination, to prepare a mannosylated chitosan, a conjugate polymer and a subsequent formulation of Cur-MCNPs. Optimized formulation prepared using RSM was evaluated for in vitro release kinetics at physiological pH 7.4 and endosomal macrophage pH 4.5; in vivo pharmacokinetic profile and targeting potential were evaluated by fluorescence microscopy.
  
  
  RESULTS
  Optimized Cur-MCNPs exhibited spherical and smooth surface with a mean particle size of 215 nm, polydispersity index of 0.381, zeta potential of + 24.37 mV and % entrapment efficiency of 82.12%. The pharmacokinetic study of optimized Cur-MCNPs showed significant improvement in the value of mean resident time (39.38 h) compared to free CUR solution (0.30 h) (p < 0.05). In vivo uptake study indicated that endocytosis took place effectively within the macrophages of reticuloendothelial system.
  
  
  CONCLUSIONS
  Thus, Cur-MCNPs could be considered as a promising delivery strategy towards active targeting of CUR to macrophages for the effective treatment of VL.
authors.affiliation: Banaras Hindu University, Indian Institute of Technology, Department of Pharmaceutics , Varanasi-221005, Uttar Pradesh , India , +91 9415811824 ; +91 542 2368428 ; bmishrabhu@rediffmail.com.
authors.forename: Pramila
authors.initials: P
authors.lastname: Chaubey
authors.forename: Ravi R
authors.initials: RR
authors.lastname: Patel
authors.forename: Brahmeshwar
authors.initials: B
authors.lastname: Mishra
mesh_terms: D000818:Animals; D001692:Biological Transport; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008358:Mannose / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D048271:Chitosan; D003474:Curcumin; D008358:Mannose
keywords: central composite design; curcumin; nanoparticles; optimization; response surface methodology; visceral leishmaniasis