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Pharmaceutical Research

, 36:134 | Cite as

Challenging the CNS Targeting Potential of Systemically Administered Nanoemulsion Delivery Systems: a Case Study with Rapamycin-Containing Fish Oil Nanoemulsions in Mice

  • Ekta Kadakia
  • Pratiksha Harpude
  • Neha Parayath
  • Dean Bottino
  • Mansoor AmijiEmail author
Research Paper
  • 3 Downloads

Abstract

Purpose

Despite extensive preclinical investigations, in-vivo properties and formulation characteristics that improve CNS drug delivery following systemic dosing of nanoemulsions remain incompletely understood.

Methods

The CNS targeting potential of systemically administered nanoemulsions was evaluated by formulating rapamycin containing fish oil nanoemulsions, and testing the combined effect of formulation characteristics such as the circulation half-life and particle size distribution, on CNS delivery of rapamycin containing fish oil nanoemulsions in mice.

Results

Results generated with rapamycin nanoemulsions suggested that circulation half-life and particle size distribution did not impact the brain targeting efficiency of rapamycin containing fish oil nanoemulsions. Further, in the absence of any improvement in the systemic exposures of rapamycin, nanoemulsions did not outperform their aqueous counterpart with respect to the extent of CNS drug delivery.

Conclusions

Our findings confirm that BBB penetration, which primarily depends on intrinsic drug-related properties, may not be significantly improved following encapsulation of drugs in nanoemulsions.

Graphical Abstract

The CNS targeting potential of systemically administered nanoemulsions was investigated by formulating various rapamycin containing fish oil nanoemulsions associated with different formulation characteristics such as the circulation half-life and particle size distribution. The targeting efficiency (TE) defined as the ratio of the brain exposures to the accompanying systemic exposures of rapamycin was estimated for each formulation following IV dosing in mice.

Key Words

CNS targeting blood-brain barrier nanoemulsions drug delivery pharmacokinetics rapamycin 

Abbreviations

Å

Angstrom

AQ

Aqueous

AUC

Area under curve

Ave

Average

°C

Degree Celsius

CL

Clearance

a

Maximum concertation

Da

Dalton

hr.

Hour

hr.*ng/g

Hour*nanogram/g

hr.*ng/mL

Hour*nanogram/ml

L

Liter

L/(hr*kg)

Liter/(hour*kilogram)

μm

Micrometer

μL

Microliter

mg/kg

Milliliter/kg

mL/min

Milliliter/min

MRT

Mean residence time

NA

Not available

NE

Nanoemulsion

ng/mL

Nanogram/ml

ng/g

Nanogram/g

nm

Nanometer

PDI

Polydispersity index

psi

Pounds per square inch

R2

Coefficient of determination

SD

Standard deviation

SE

Standard error

w/v

Weight/volume

Notes

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, School of PharmacyNortheastern UniversityBostonUSA
  2. 2.Translational Modeling & Simulation, Quantitative Clinical Pharmacology, Takeda PharmaceuticalsCambridgeUSA

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