title: Nanostructured lipid carrier versus solid lipid nanoparticles of simvastatin: comparative analysis of characteristics, pharmacokinetics and tissue uptake.
abstract: Nanostructured lipid carrier (NLC) system of simvastatin was investigated for improvement in release, pharmacokinetics and biodistribution over its solid lipid nanoparticles (SLN). The NLC formulations prepared by solvent injection technique were optimized by 2(3) full factorial design. Optimized NLC was deduced on the basis of dependent variables that were analyzed using Design expert 8.0.2 software (Stat Ease, Inc., USA). Pareto charts and response surface plots were utilized to study the effect of variables on the response parameters. The optimized NLC was a suspension of nanosized homogeneous particles with significantly higher entrapment efficiency (>90%) and lower recrystallization properties (p<0.01) than SLNs. The pharmacokinetic parameters of Tc(99) labeled optimized NLC in mice, obtained using Quickcal software (Plexus, India) revealed 4.8 folds increase in bioavailability as compared to simvastatin suspension and 2.29 folds as compared to SLNs. Biodistribution study revealed preferential accumulation of NLC in the liver and this is advantageous because liver is the target organ for simvastatin. IVIVC studies demonstrated level A correlation between in vitro release and percent drug absorbed. This investigation demonstrated the superiority of NLC over SLN for improved oral delivery and it was deduced that the liquid lipid, oleic acid was the principal formulation factor responsible for the improvement in characteristics, pharmacokinetics and biodistribution of NLCs.
authors.affiliation: Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh 281001, India.
authors.forename: Radheshyam
authors.initials: R
authors.lastname: Tiwari
authors.forename: Kamla
authors.initials: K
authors.lastname: Pathak
mesh_terms: D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D019821:Simvastatin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D000960:Hypolipidemic Agents; D008055:Lipids; D019821:Simvastatin