title: External manipulation of nanostructure in photoresponsive lipid depot matrix to control and predict drug release in vivo.
abstract: On-demand drug delivery systems are highly promising to control the time-course of drug release and ultimately optimize drug concentration time profiles in patients. Lipid based lyotropic liquid crystalline mesophases have demonstrated exceptional responsiveness to external stimuli such as heat, pH and light. Our objective was to quantitatively characterize the time-course of light activated drug release from near infrared (NIR) activated photothermal systems using ex vivo and in vivo studies. Photoresponsive hybrid gold nanorod-liquid crystalline matrices were prepared and loaded into custom-made implants which were inserted into subcutaneous tissues in rats. Time resolved SAXS studies showed the abdomen to be the best site of implantation to achieve in vivo activation of the subcutaneous dose from by the NIR laser. External control of drug release was achieved via NIR laser light and plasma concentrations of the model drug were determined over time. Laser activation achieved a phase change of the photoresponsive formulations and thereby a considerable change in the rate of drug release. Population pharmacokinetic modeling of all results simultaneously revealed a two stage release process unique to these liquid crystalline matrices. The developed structural model was able to successfully describe also the results of our previous study in 2009 where a change in temperature was utilized to trigger subcutaneous drug release. Thus, modeling of the data proved to be a valuable analytical tool which provided a quantitative understanding of the time-course of drug release in vivo and will be essential in the development of these matrices as on-demand release systems.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia; Food and Soft Materials Science, Institute of Food, Nutrition & Health, ETH Zurich, Schmelzbergstrasse 9, 8092 Zürich, Switzerland.
authors.forename: Wye-Khay
authors.initials: WK
authors.lastname: Fong
authors.affiliation: Australian Nuclear Science and Technology Organisation, Menai, NSW 2234, Australia.
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Hanley
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Thierry
authors.affiliation: SAXS/WAXS beamline, Australian Synchrotron, Clayton, Victoria, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Hawley
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: ben.boyd@monash.edu.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia; School of Pharmacy and Pharmaceutical Sciences, SUNY Buffalo, NY, USA. Electronic address: cornelia.landersdorfer@monash.edu.
authors.forename: Cornelia B
authors.initials: CB
authors.lastname: Landersdorfer
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005947:Glucose / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006046:Gold / Q000737:chemistry; D007259:Infrared Rays; D007834:Lasers; D050866:Liquid Crystals / Q000737:chemistry*; D008297:Male; D043942:Nanotubes / Q000737:chemistry*; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D006046:Gold; D005947:Glucose
keywords: Cubic phase; Lipid; Liquid crystalline mesophase; Pharmacokinetic modeling; Photothermal activation; Triggerable drug delivery