Development and characterization of a novel lipohydrogel nanocarrier: repaglinide as a lipophilic model drug.
OBJECTIVE
Solid lipid nanoparticles (SLNs) are highly susceptible to phagocytosis by reticuloendothelial system (RES). To overcome this problem, a novel hydrogel-coated SLNs structure was developed and evaluated in this study.


METHODS
Solid lipid nanoparticles surface was coated with chitosan, via electrostatic attraction with the negatively charged SLNs surface. The resulting polymer-coated SLNs then hosted an inorganic poly-anionic agent, tripolyphosphate, to form the final lipohydrogel structure.


RESULTS
Compared with the bare SLNs, lipohydrogel nanoparticles (LHNs) showed a significant increase in size and zeta potential. The release profile showed lower burst release and lower release rate for LHNs compared with SLNs. LHNs nanoparticles released the model antidiabetic drug, repaglinide, in a more sustained manner with lower burst effect compared with the corresponding SLN structure. Cytotoxicity studies via cell culture and MTT assay revealed no bio-toxicity of the SLNs and LHNs. In addition, intravenous administration of repaglinide-loaded SLNs and LHNs in rats showed longer drug residence time in circulation for LHNs, a trend also evident for the blood glucose level-time profile.


CONCLUSIONS
The particle size, zeta potential, FTIR and microscopy data demonstrated the formation of the supposed lipohydrogel nanoparticles. All these benefits of LHNs propose it as a promising candidate for controlled release of the drugs.
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.|Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, Iran.
Hossein Ali
HA
Ebrahimi
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Yousef
Y
Javadzadeh
Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan, Iran.|Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Mehrdad
M
Hamidi
Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Mohammad
M
Barzegar Jalali
D061605:Administration, Intravenous; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D020100:Hydrogels; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D008297:Male; D051379:Mice; D036103:Nanotechnology; D010316:Particle Size; D010880:Piperidines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D011122:Polyphosphates / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
D001786:Blood Glucose; D002219:Carbamates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D007004:Hypoglycemic Agents; D008055:Lipids; D010880:Piperidines; D011122:Polyphosphates; C072379:repaglinide; D048271:Chitosan; C005692:triphosphoric acid
chitosan; lipohydrogel; nanocarrier; repaglinide; solid lipid nanoparticles