title: A novel approach to enhance the mucoadhesion of lipid drug nanocarriers for improved drug delivery to the buccal mucosa.
abstract: Targeted drug delivery to the buccal mucosa offers distinct advantages over oral delivery to the gastrointestinal tract including by-passing hepatic first-pass metabolism. However, the buccal route is often limited by low bioavailability, low drug loading and reduced residence time due to salivary excretion and clearance. To overcome these limitations, a novel mucoadhesive formulation based on liquid crystalline nanoparticles was designed. Utilising a pH induced in situ transition from a stable vesicle formulation to dispersed inverse hexagonal phase nanoparticles (hexosomes) enhanced adsorption onto the mucosal surface was enabled. Firstly, the phase behaviour of the amphiphilic lipid phytantriol (PHY) and oleic acid (OA) was assessed from pH 2-9 using small-angle X-ray scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) to determine the appropriate composition for the vesicle to hexosome transition. The colloidal stability of the formulation was determined using turbidity studies. Dispersions comprising 30% w/w OA in PHY were able to form stable vesicles at pH 8 and transition to hexosomes when exposed to pH<7 (as encountered on the buccal mucosal surface). Subsequent ex vivo studies utilising excised porcine buccal tissue indicated significant retention of the in situ-formed PHY/OA hexosomes when compared to control DOPC vesicles (p<0.005), confirmed independently using confocal fluorescence microscopy, radioactive scintillation counting and HPLC analysis for incorporated drug. Thus, a novel approach providing a stable vesicle formulation, with in situ transformation to mucoadhesive hexosomes has been identified with the potential to enhance drug delivery to mucosal surfaces.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, Australia.
authors.forename: Joanne D
authors.initials: JD
authors.lastname: Du
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, Australia.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Salentinig
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, Australia. Electronic address: tri-hung.nguyen@monash.edu.
authors.forename: Tri-Hung
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, Australia. Electronic address: ben.boyd@monash.edu.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
mesh_terms: D000268:Adhesiveness; D000818:Animals; D003102:Colloids; D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D005233:Fatty Alcohols / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry* / Q000493:pharmacokinetics; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009061:Mouth Mucosa / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D019301:Oleic Acid / Q000737:chemistry; D010316:Particle Size; D044367:Phase Transition; D013499:Surface Properties; D034421:Sus scrofa; D014221:Triamcinolone / Q000008:administration & dosage
chemical_list: D003102:Colloids; D004337:Drug Carriers; D005233:Fatty Alcohols; D008055:Lipids; D014221:Triamcinolone; D019301:Oleic Acid; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol
keywords: Colloidal stability; Liquid crystal; Mucoadhesion; Nanoparticles; Sustained-release