title: Pharmacoscintigraphic evaluation of potential of lipid nanocarriers for nose-to-brain delivery of antidepressant drug.
abstract: Efficacy of antidepressants relies upon their continued presence at the site of action (brain) over a prolonged period of time. The BBB restricts the access of antidepressants to the brain on oral as well as intravenous administration. Direct delivery (by-passing the BBB) of antidepressant drugs can increase the CSF concentration with concomitant reduction in dose and side effects. Intranasal administration of nanostructured lipid carriers (NLC) containing antidepressant drug circumvent the BBB and maintain the prolonged release at the site of action. The aim of the present study was to evaluate the enhancement in brain uptake of NLC containing duloxetine (DLX) after intranasal administration. Duloxetine loaded NLC (DLX-NLC) was evaluated pharmacoscintigraphically for drug targeting potential (DTP), drug targeting efficiency (DTE) and biodistribution studies in different organs including brain. The radiolabeling efficiency of DLX and DLX-NLC was found to be 98.41 ± 0.96 and 98.87 ± 0.82 after 30 min, respectively. The biodistribution studies exhibited higher percentage of radioactivity/g for DLX-NLC formulations in brain as compared with the DLX. The higher DTP (86.80%) and DTE (757.74%) suggested that DLX-NLC formulation has a better brain targeting efficiency than DLX solution (DTP=65.12%; DTE=287.34%) when administered intranasally. Moreover, the intranasal administration exhibited about 8-times higher concentration of DLX in brain when compared with the intravenous administration of DLX solution. The intranasal NLC containing DLX can be employed as an effective method for the treatment of depression.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India; Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
authors.forename: M Intakhab
authors.initials: MI
authors.lastname: Alam
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India. Electronic address: sbaboota@rediffmail.com.
authors.forename: Sanjula
authors.initials: S
authors.lastname: Baboota
authors.affiliation: Pharmacy Department, Oman Medical College, Bowsher campus, Muscat, Oman.
authors.forename: Alka
authors.initials: A
authors.lastname: Ahuja
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
authors.forename: Mushir
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
authors.forename: Javed
authors.initials: J
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
authors.forename: Jasjeet K
authors.initials: JK
authors.lastname: Sahni
authors.affiliation: Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences (INMAS), Brig SK Mazumdar Marg, Delhi, India.
authors.forename: Aseem
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000068736:Duloxetine Hydrochloride; D005260:Female; D005989:Glycerides / Q000737:chemistry; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D009297:Nasal Mucosa / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D011817:Rabbits; D011877:Radionuclide Imaging; D017208:Rats, Wistar; D013667:Technetium; D013876:Thiophenes / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000928:Antidepressive Agents; D004337:Drug Carriers; D005989:Glycerides; D011108:Polymers; D011409:Propylene Glycols; D013876:Thiophenes; C584816:capryol propylene glycol monocaprylate; C048159:glyceryl monostearate; D013667:Technetium; D000068736:Duloxetine Hydrochloride
keywords: Biodistribution; DTE; DTP; Pharmacoscintigraphy; Radiolabeling efficiency