Preparation, characterization and antibacterial activities of chitosan, N-trimethyl chitosan (TMC) and N-diethylmethyl chitosan (DEMC) nanoparticles loaded with insulin using both the ionotropic gelation and polyelectrolyte complexation methods.
TMC and DEMC, quaternized derivatives of chitosan, have been shown to have penetration enhancement properties and able to open the tight junctions of the intestinal epithelia at neutral and alkaline pH environments. The use of the nanoparticulate systems has the advantage of protecting the peptidic drugs from the harsh environment of the gastrointestinal tract. Hence, the aim of this study was to synthesize and characterize TMC and DEMC, both with quaternization degrees of 50+/-5%, which were then used to prepare insulin nanoparticles with two different methods: ionotropic gelation and the polyelectrolyte complexation (PEC) techniques. The obtained nanoparticles were then characterized for size, zeta potential, insulin loading and release as well as antibacterial activities. The results showed that nanoparticles prepared by the PEC method had higher insulin loading efficiency and zeta potential than those made by the ionotropic gelation method and may subsequently be used for further in vitro, ex vivo and in vivo studies. Moreover, the antibacterial studies suggest that the polymers in free form have higher antibacterial activity against Gram-positive bacteria than in the nanoparticulate form.
Sadeghi
A M M
AM
Division of Pharmaceutical Technology, Leiden University, P.O. Box 9502, 2300RA Leiden, The Netherlands.
Dorkoosh
F A
FA
Avadi
M R
MR
Saadat
P
P
Rafiee-Tehrani
M
M
Junginger
H E
HE
D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D004563:Electrochemistry; D004573:Electrolytes; D005079:Excipients; D005782:Gels; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D013211:Staphylococcus aureus / Q000187:drug effects
D004573:Electrolytes; D005079:Excipients; D005782:Gels; D007004:Hypoglycemic Agents; D007328:Insulin; C118071:N-trimethyl chitosan chloride; C530700:dimethylethylchitosan; D048271:Chitosan