title: Formulation of olfactory-targeted microparticles with tamarind seed polysaccharide to improve nose-to-brain transport of drugs.
abstract: Targeted delivery and retention of drug formulations in the olfactory mucosa, the target site for nose-to-brain drug absorption is a major challenge due to the geometrical complexity of the nose and nasal clearance. Recent modelling data indicates that 10μm-sized microparticles show maximum deposition in the olfactory mucosa. In the present study we tested the hypothesis that 10μm-sized mucoadhesive microparticles would preferentially deposit on, and increase retention of drug on, the olfactory mucosa in a novel 3D-printed human nasal-replica cast under simulated breathing. The naturally occurring mucoadhesive polymer, tamarind seed polysaccharide (TSP) was used to formulate the microparticles using a spray drying technique. Physicochemical properties of microparticles such as size, morphology and mucoadhesiveness was investigated using a combination of laser diffraction, electron microscopy and texture-analysis. Furthermore, FITC-dextrans (5-40kDa) were incorporated in TSP-microparticles as model drugs. Size-dependent permeability of the FITC-dextrans was observed ex vivo using porcine nasal mucosa. Using the human nasal-replica cast, greater deposition of 10μm TSP-microparticles in the olfactory region was observed compared to TSP-microparticles 2μm in size. Collectively, these findings support our hypothesis that 10μm-sized mucoadhesive microparticles can achieve selective deposition and retention of drug in the olfactory mucosa.
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 56 Dunedin 9054, New Zealand. Electronic address: yarsa131@student.otago.ac.nz.
authors.forename: Sasi B
authors.initials: SB
authors.lastname: Yarragudi
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 56 Dunedin 9054, New Zealand. Electronic address: richter.robert@aol.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Richter
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 56 Dunedin 9054, New Zealand. Electronic address: leehe949@student.otago.ac.nz.
authors.forename: Helen
authors.initials: H
authors.lastname: Lee
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 56 Dunedin 9054, New Zealand. Electronic address: greg.walker@otago.ac.nz.
authors.forename: Greg F
authors.initials: GF
authors.lastname: Walker
authors.affiliation: Department of Anatomy, Otago School of Medical Sciences, University of Otago, P.O. Box 56 Dunedin 9054, New Zealand; Brain Health Research Centre, University of Otago, P.O. Box 56 Dunedin 9054, New Zealand. Electronic address: andrew.clarkson@otago.ac.nz.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Clarkson
authors.affiliation: Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: hkmu551@aucklanduni.ac.nz.
authors.forename: Haribalan
authors.initials: H
authors.lastname: Kumar
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 56 Dunedin 9054, New Zealand; Brain Health Research Centre, University of Otago, P.O. Box 56 Dunedin 9054, New Zealand. Electronic address: shakila.rizwan@otago.ac.nz.
authors.forename: Shakila B
authors.initials: SB
authors.lastname: Rizwan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain; D016503:Drug Delivery Systems; D006801:Humans; D009297:Nasal Mucosa; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D011134:Polysaccharides / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D013552:Swine; D029861:Tamarindus / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D011134:Polysaccharides
keywords: Intranasal drug delivery; Microparticles; Mucoadhesive; Nose-to-brain drug delivery; Olfactory targeting; Tamarind seed polysaccharide