title: Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box-Behnken experimental design.
abstract: Indomethacin chitosan nanoparticles (NPs) were developed by ionotropic gelation and optimized by concentrations of chitosan and tripolyphosphate (TPP) and stirring time by 3-factor 3-level Box-Behnken experimental design. Optimal concentration of chitosan (A) and TPP (B) were found 0.6mg/mL and 0.4mg/mL with 120min stirring time (C), with applied constraints of minimizing particle size (R1) and maximizing encapsulation efficiency (R2) and drug release (R3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R1, while factor A has a negative impact on R2 and R3. Interaction of AB was negative on R1 and R2 but positive on R3. The factor AC was having synergistic effect on R1 and on R3, while the same combination had a negative effect on R2. The interaction BC was positive on the all responses. NPs were found in the size range of 321-675nm with zeta potentials (+25 to +32mV) after 6 months storage. Encapsulation, drug release, and content were in the range of 56-79%, 48-73% and 98-99%, respectively. In vitro drug release data were fitted in different kinetic models and pattern of drug release followed Higuchi-matrix type.
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohd
authors.initials: M
authors.lastname: Abul Kalam
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdul Arif
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Shahanavaj
authors.initials: S
authors.lastname: Khan
authors.affiliation: National Center of Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City of Science and Technology, Riyadh, Saudi Arabia.
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Almalik
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia. Electronic address: aalshamsan@ksu.edu.sa.
authors.forename: Aws
authors.initials: A
authors.lastname: Alshamsan
mesh_terms: D002214:Capsules; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D057927:Hydrophobic and Hydrophilic Interactions; D007213:Indomethacin / Q000737:chemistry*; D007700:Kinetics; D008962:Models, Theoretical; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011122:Polyphosphates / Q000737:chemistry
chemical_list: D002214:Capsules; D004337:Drug Carriers; D011122:Polyphosphates; D048271:Chitosan; C005692:triphosphoric acid; D007213:Indomethacin
keywords: Box–Behnken design; Chitosan; Indomethacin; Nanoparticles