Optimization of artemether-loaded NLC for intranasal delivery using central composite design

The objective of the study was to optimize artemether-loaded nanostructured lipid carriers (ARM-NLC) for intranasal delivery using central composite design. ARM-NLC was prepared by microemulsion method with optimized formulation having particle size of 123.4 nm and zeta potential of −34.4 mV. Differ...

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Bibliographic Details
Published in:Drug delivery 2015-10, Vol.22 (7), p.940-954
Main Authors: Jain, Kunal, Sood, Sumeet, Gowthamarajan, Kuppusamy
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Antimalarials - administration & dosage
Antimalarials - pharmacokinetics
Antimalarials - toxicity
Artemether
Artemisinins - administration & dosage
Artemisinins - pharmacokinetics
Artemisinins - toxicity
Brain - metabolism
Calorimetry, Differential Scanning
central composite design
Chemistry, Pharmaceutical - methods
Delayed-Action Preparations
Drug Carriers - chemistry
Drug Delivery Systems
intranasal
lipid
Lipids - chemistry
Male
nanoparticle
Nanoparticles
Nasal Mucosa - drug effects
Nasal Mucosa - metabolism
Original
Particle Size
Rats
Rats, Wistar
Sheep
Tissue Distribution
X-Ray Diffraction
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Summary:The objective of the study was to optimize artemether-loaded nanostructured lipid carriers (ARM-NLC) for intranasal delivery using central composite design. ARM-NLC was prepared by microemulsion method with optimized formulation having particle size of 123.4 nm and zeta potential of −34.4 mV. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that drug existed in amorphous form in NLC formulation. In vitro cytotoxicity assay using SVG p12 cell line and nasal histopathological studies on sheep nasal mucosa indicated the developed formulations were non-toxic and safe for intranasal administration. In vitro release studies revealed that NLC showed sustained release up to 96 h. Ex vivo diffusion studies using sheep nasal mucosa revealed that ARM-NLC had significantly lower flux compared to drug solution (ARM-SOL). Pharmacokinetic and brain uptake studies in Wistar rats showed significantly higher drug concentration in brain in animals treated intranasally (i.n.) with ARM-NLC. Brain to blood ratios for ARM-NLC (i.n.), ARM-SOL (i.n.) and ARM-SOL (i.v.) were 2.619, 1.642 and 0.260, respectively, at 0.5 h indicating direct nose to brain transport of ARM. ARM-NLC showed highest drug targeting efficiency and drug transport percentage of 278.16 and 64.02, respectively, which indicates NLC had better brain targeting efficiency compared to drug solution.
ISSN:1071-7544
1521-0464
DOI:10.3109/10717544.2014.885999