title: Analgesic efficacy and safety of DALDA peptide analog delivery to the brain using oil-in-water nanoemulsion formulation.
abstract: OBJECTIVE
  The main objective of this study was to develop and evaluate therapeutic efficacy and safety following systemic delivery of a peptide analgesic into the CNS using an oil-in-water nanoemulsion system.
  
  
  METHODS
  We have formulated a safe and effective, omega-3 rich polyunsaturated fatty acid containing oil-in-water nanoemulsion formulation, for encapsulating and delivering chemically-modified DALDA, a potent mu-opioid peptide analogue, to the CNS. One of the challenges with CNS delivery is the lack of a non-invasive bioanalytical technique to confirm CNS uptake and therapeutic efficacy. Using blood oxygen-level dependent (BOLD) functional magenetic resonance imaging (fMRI), we provide quantitative evidence of nanoemulsion-based delivery and analgesic activity of DALDA analogue in capsaicin-induced awake rat model of pain.
  
  
  RESULTS
  Nanoemulsion formulation effectively encapsulated the modified analgesic peptide and demonstrated efficacy in the capsaicin- pain induced functional magnetic resonance imaging model in rodents. Preliminary safety evaluations show that the nanoemulsion system was well tolerated and did not cause any acute negative effects.
  
  
  CONCLUSIONS
  Overall, these results show tremendous opportunity for the development of modified peptide analgesic-encapsulated nanoemulsion formulations for CNS delivery and therapeutic efficacy.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, 02115, USA.
authors.forename: Lipa
authors.initials: L
authors.lastname: Shah
authors.forename: Praveen
authors.initials: P
authors.lastname: Kulkarni
authors.forename: Craig
authors.initials: C
authors.lastname: Ferris
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions; D008279:Magnetic Resonance Imaging; D008297:Male; D008815:Mice, Inbred Strains; D049329:Nanostructures / Q000737:chemistry*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*
chemical_list: D000700:Analgesics; D004337:Drug Carriers; D004655:Emulsions; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C063076:tyrosyl-arginyl-phenylalanyl-lysinamide; D002211:Capsaicin