Formulation and delivery of itraconazole to the brain using a nanolipid carrier system.
The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol(®) ATO 5 and Transcutol(®) HP were selected as the lipid phase, and Tween(®) 80 and Solutol(®) HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, -18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery.
School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
Wei Meng
WM
Lim
School of Pharmacy, Taylor's University, Selangor, Malaysia.
Paruvathanahalli Siddalingam
PS
Rajinikanth
School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
Chitneni
C
Mallikarjun
School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
Yew Beng
YB
Kang
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage; D001812:Blood-Brain Barrier / Q000378:metabolism*; D004075:Diglycerides / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D005026:Ethylene Glycols / Q000737:chemistry*; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D014018:Tissue Distribution
D000935:Antifungal Agents; D004075:Diglycerides; D005026:Ethylene Glycols; D053769:Nanocapsules; D011136:Polysorbates; D013229:Stearic Acids; D017964:Itraconazole; D011092:Polyethylene Glycols; C067028:Solutol HS 15; C010111:carbitol; C009032:precirol
brain delivery; lipid nanoparticles; nanostructured lipid carrier