title: Self-nanoemulsifying drug delivery system of docosahexanoic acid: development, in vitro, in vivo characterization.
abstract: BACKGROUND
  Docosahexanoic acid (DHA) is an essential omega-3 fatty acid for normal brain development and its use has increased considerably in recent years.
  
  
  OBJECTIVE
  The aim of this study is to develop and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) of DHA for improved palatability, dispersibility and bioavailability.
  
  
  METHODS
  The SNEDDS were prepared and evaluated for miscibility, employing different combinations of olive oil and soyabean oil as oil phase, Span 80, Span 20, soya phosphatidylcholine, Labrafil M 1944 CS as surfactants while Tween 80, PEG 400, Cremophor RH40 and propylene glycol as cosurfactants. Thermodynamically stable SNEDDS were characterized for dispersibility, self-emulsification time, droplet size, zeta potential along with sensory analysis. The optimized formulation was subjected to ex vivo and in vivo evaluation such as intestinal permeability, memory performance test, brain concentration and histopathology studies.
  
  
  RESULTS
  The optimized SNEDDS formulation showed emulsification time of 27 ± 4.7 s with droplet size of 17.6 ± 3.5 nm and zeta potential of -37.6 ± 0.5 mV. Intestinal absorption study depicted 18.3%, 21.5%, 41.5%, 98.7% absorption of DHA with SNEDDS-based formulation in comparison to 8.2%, 15.1%, 28.8%, 46.1% absorption of DHA with oil-based marketed formulation after 0.5, 1, 2 and 4 h. DHA concentration in brain homogenate was found to be increased to 2.6-fold in comparison to DHA-marketed formulation. This could be ascribed to enhanced dispersibility and bioavailability of DHA from nanosized formulation.
  
  
  CONCLUSIONS
  The developed formulation led to enhanced dispersibility and bioavailability of DHA due to the formation of nanodroplets.
authors.affiliation: a Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab , India.
authors.forename: Ritika
authors.initials: R
authors.lastname: Puri
authors.affiliation: a Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab , India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Mahajan
authors.affiliation: a Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab , India.
authors.forename: Nikhil Shri
authors.initials: NS
authors.lastname: Sahajpal
authors.affiliation: a Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab , India.
authors.forename: Harjeet
authors.initials: H
authors.lastname: Singh
authors.affiliation: a Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab , India.
authors.forename: Harmanpreet
authors.initials: H
authors.lastname: Singh
authors.affiliation: a Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab , India.
authors.forename: Subheet Kumar
authors.initials: SK
authors.lastname: Jain
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D007408:Intestinal Absorption; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D049329:Nanostructures / Q000737:chemistry*; D000069463:Olive Oil / Q000737:chemistry; D051381:Rats; D013024:Soybean Oil / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D014783:Viscosity
chemical_list: D004655:Emulsions; D000069463:Olive Oil; D013501:Surface-Active Agents; D004281:Docosahexaenoic Acids; D013024:Soybean Oil
keywords: Dispersibility; intestinal permeability; memory performance test; self-emulsification time