Chitosan derivatives as effective nanocarriers for ocular release of timolol drug.
The aim of the present study was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with succinic anhydride (CSUC) and 2-carboxybenzaldehyde (CBCS) as appropriate nanocarriers for ocular release of timolol maleate (Tim). Drug nanoencapsulation was performed via ionic crosslinking gelation of the used carriers and sodium tripolyphosphate (TPP). Nanoparticles with size ranged from about 190 to 525 nm were prepared and it was found that the formed size was directly depended on the used carrier and their ratios with TPP. For CS derivatives it was found that as the amount of TPP increased, the particle size increased too, while both derivatives proceeded to nanoparticles with smaller size than that of neat CS. The interactions between carriers and TPP were studied theoretically using all-electron calculations within the framework of density functional theory (DFT). In most of nanoparticles formulations, Tim was entrapped in amorphous form, while the drug entrapment efficiency was higher in CBCS derivative.It was indicated that Tim release rate depended mainly on the used carrier, particle size of prepared nanocarriers and drug loading. From the theoretical release data analysis, it was found that the Tim release was a stagewise procedure with drug diffusion being the dominant release mechanism for each stage.
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
Panoraia I
PI
Siafaka
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
Alexandra
A
Titopoulou
Molecular Engineering Laboratory, Department of Physics, University of Patras, Patra GR-26500, Greece.
Emmanuel N
EN
Koukaras
Laboratory of Inorganic Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
Margaritis
M
Kostoglou
Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str 6, Pallini Attikis, GR-15351 Attiki, Greece.
Efthimios
E
Koutris
Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str 6, Pallini Attikis, GR-15351 Attiki, Greece.
Evangelos
E
Karavas
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece. Electronic address: dbic@chem.auth.gr.
Dimitrios N
DN
Bikiaris
D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000031:analogs & derivatives*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005123:Eye; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011122:Polyphosphates / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013387:Succinic Anhydrides / Q000737:chemistry; D013999:Timolol / Q000008:administration & dosage*; D014961:X-Ray Diffraction
D004337:Drug Carriers; D011122:Polyphosphates; D013387:Succinic Anhydrides; C031801:succinic anhydride; D013999:Timolol; D048271:Chitosan; C005692:triphosphoric acid
Chitosan derivatives; Nanoparticles; Ocular release; Timolol drug