Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain

Abstract

Context & Objective: The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug.

Methods: Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study.

Results: Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential −18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers.

Conclusions: IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

• Bioavailability
• morris water
• nanomedicine
• nanoprecipitation
• stability study

Acknowledgements

The authors are very thankful to Principal, Bharati Vidyapeeth College of Pharmacy, Kolhapur for providing necessary facilities for this research work. The authors are highly thankful to Takeda Pharmaceuticals Ltd Italy for providing Idebenone as a gift sample. Authors are thankful to Gattefossé (Cedex, France) for providing solid lipid Precirol ATO 5 and surfactant Labrasol as gift samples. Authors are also thankful to Sasol Germany GmbH and S. D. Fine Chemicals Ltd, India for providing gift samples of oil Miglyol 840 and surfactant Tween 80, respectively.

Declaration of interest

The authors declare that they have no conflict of interest.

Supplementary material available online

Supplementary Figure 6.