Optimization of physicochemical parameters influencing the fabrication of protein-loaded chitosan nanoparticles.
OBJECTIVE
In the development of controlled-release protein therapeutics, the high encapsulation of proteins into biodegradable nanoparticles with uniform size in an anhydrous process along with an excellent redispersion is of practical interest. The objective of this work was to study the physicochemical and in vitro release properties of chitosan nanoparticles with different molecular weights (low, medium and high) using bovine serum albumin (BSA) as a model protein for developing nanoparticle formulations that were stable and reproducible after lyophilization.


METHODS
The BSA-loaded chitosan nanoparticles were prepared by an ionic gelation method using pentasodium tripolyphosphate as the polyanions. The physicochemical properties and in vitro release kinetics of the nanoparticles were evaluated along with Fourier transform infrared spectroscopy studies. Furthermore, the nanoparticles were freeze-dried for long-term stability in the formulation. To optimize the size of the freeze-dried nanoparticles after redispersion, various types of lyoprotectants (natural and synthetic) were tested in varying concentration in the process of lyophilization.


RESULTS
The dynamic light scattering measurements revealed the increase in size of chitosan nanoparticles with the increase in molecular weight of chitosan with no significant change, irrespective of the concentration of BSA entrapped. In addition, the entrapment efficiency of the nanoparticles increased with the increasing molecular weight of chitosan and BSA concentration. By contrast, the redispersity of the freeze-dried samples resulted in further increase of the mean diameter of the nanoparticles.


CONCLUSIONS
Among the various types of lyoprotectants (natural and synthetic) examined, sucrose proved to be very effective in reducing the size of freeze-dried nanoparticles on redispersion without significant change in surface charge of nanoparticles. Finally, the in vitro release kinetics of BSA from nanoparticles of different molecular weights of chitosan, with and without sucrose, was evaluated and found to depend upon the molecular weight of chitosan.
Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar, Orissa, India.
Mallaredy
M
Vandana
Sanjeeb K
SK
Sahoo
D000818:Animals; D002417:Cattle; D048271:Chitosan / Q000737:chemistry*; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013395:Sucrose / Q000737:chemistry
D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D013395:Sucrose; D048271:Chitosan