Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: Role of docosahexaenoic acid

Eur J Pharm Biopharm. 2015 Oct;96:363-79. doi: 10.1016/j.ejpb.2015.08.008. Epub 2015 Aug 28.


Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection are reported. MEs prepared by simple solution exhibited a globule size <20nm, negative zeta potential and good stability. The docosahexaenoic acid (DHA) ME revealed high and rapid ex vivo permeation of drugs through sheep nasal mucosa. Intranasal DHA ME resulted in high brain concentrations and 10.76 (ABZ-SO) and 3.24 (CUR) fold enhancement in brain area-under-the-curve (AUC) compared to intravenous DHA MEs at the same dose. Direct nose to brain transport (DTP) of >95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (P<0.05) suggested the role of DHA in aiding nose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10ng/mL) DHA ME in vitro on Taenia solium cysts was confirmed by complete ALP inhibition and disintegration of cysts at 96h. Considering that the brain concentration at 24h was 1400±160.1ng/g (ABZ-SO) and 120±35.2ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery.

Keywords: Acetonitrile (PubChem CID: 6342); Albendazole sulfoxide; Albendazole sulfoxide (PubChem CID: 83969); Capmul MCM (PubChem CID: 3033877); Curcumin; Curcumin (PubChem CID: 969516); Direct nose to brain transport (DTP); Docosahexaenoic acid (DHA); Docosahexaenoic acid (PubChem CID: 175542); Drug targeting efficiency (DTE); Ethanol (PubChem CID: 702); Ex vivo permeation; Intranasal microemulsions; N,N-dimethylacetamide (PubChem CID: 31374); Neurocysticercosis; Nose to brain delivery; Propylene glycol (PubChem CID: 1030); Taenia solium cyst.; Tween 80 (PubChem CID: 5281955).

MeSH terms

  • Administration, Intranasal
  • Albendazole / administration & dosage
  • Albendazole / analogs & derivatives*
  • Albendazole / chemistry
  • Albendazole / metabolism
  • Albendazole / pharmacokinetics
  • Animals
  • Anthelmintics / administration & dosage*
  • Anthelmintics / chemistry
  • Anthelmintics / metabolism
  • Anthelmintics / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / ultrastructure
  • Brain / drug effects
  • Brain / metabolism
  • Curcumin / administration & dosage*
  • Curcumin / chemistry
  • Curcumin / metabolism
  • Curcumin / pharmacokinetics
  • Docosahexaenoic Acids / chemistry*
  • Drug Combinations
  • Drug Compounding
  • Drug Delivery Systems*
  • Drug Stability
  • Emulsions
  • Female
  • In Vitro Techniques
  • Male
  • Nasal Absorption
  • Neurocysticercosis / blood
  • Neurocysticercosis / drug therapy
  • Neurocysticercosis / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Pharmaceutical Vehicles / chemistry
  • Rats, Sprague-Dawley
  • Sheep, Domestic
  • Tissue Distribution


  • Anthelmintics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Combinations
  • Emulsions
  • Pharmaceutical Vehicles
  • Docosahexaenoic Acids
  • Albendazole
  • Curcumin
  • albendazole sulfoxide