Methotrexate loading in chitosan nanoparticles at a novel pH: Response surface modeling, optimization and characterization.
The aim of this study was to assess the feasibility of employing a novel but critical formulation pH (6.2) to encapsulate an anionic model drug (methotrexate, MTX) into chitosan(Cs)-tripolyphosphate nanoparticles(NPs). A response surface methodology using a three-level full factorial design was applied studying the effects of two independent variables namely; Cs concentration and MTX concentration. The responses investigated were the entrapment efficiency (EE%), mean hydrodynamic particle size (PS), polydispersity index (PDI) and zeta potential (ZP). In order to simultaneously optimize the series of models obtained, the desirability function approach was applied with a goal to produce high percent of MTX encapsulated into highly charged Cs-TPP NPs of homogenous optimum PS. MTX-loaded CsNPs were successfully prepared at the novel pH applied. The suggested significant models were found quadratic for EE, PS and ZP responses, while 2-factor interaction model for PDI. The optimization overlay graph showed that the maximum global desirability, D=0.856, was reached when the conditions were set at high Cs and MTX concentration. Thus, the use of such optimized conditions, at this novel pH, achieved a maximum drug EE% (73.38%) into NPs characterized by optimum PS (232.6nm), small PDI value (0.195) and highly surface charged (+18.4mV).
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Abassiah, Cairo 11566, Egypt. Electronic address: Dr.Rania@pharma.asu.edu.eg.
Rania A
RA
Hashad
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Abassiah, Cairo 11566, Egypt. Electronic address: raniaaziz@pharma.asu.edu.eg.
Rania A H
RA
Ishak
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Abassiah, Cairo 11566, Egypt. Electronic address: Ahmed.Gnedy@pharma.asu.edu.eg.
Ahmed S
AS
Geneidi
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Abassiah, Cairo 11566, Egypt; Department of Pharmaceutical Technology, Faculty of Pharmacy, German University in Cairo, Egypt. Electronic address: samar_holayel@yahoo.com.
Samar
S
Mansour
D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry*; D003956:Dialysis; D065546:Drug Liberation; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D008727:Methotrexate / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017550:Spectroscopy, Fourier Transform Infrared; D013223:Statistics as Topic
D048271:Chitosan; D008727:Methotrexate
Chitosan; Chitosan (PubChem CID:71853); Methotrexate; Methotrexate sodium (PubChem CID: 11329481); Nanoparticles; Optimization; Response surface methodology; Tripolyphosphate (PubChem CID: 24455); pH value