1. Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery.
- Author
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Eisenbrey JR, Burstein OM, Kambhampati R, Forsberg F, Liu JB, and Wheatley MA
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents metabolism, Aorta diagnostic imaging, Aorta metabolism, Chemistry, Pharmaceutical, Contrast Media chemistry, Contrast Media metabolism, Doxorubicin chemistry, Doxorubicin metabolism, Drug Compounding, Half-Life, Injections, Intravenous, Kidney diagnostic imaging, Kidney metabolism, Kinetics, Microscopy, Confocal, Particle Size, Polyesters, Rabbits, Rats, Rats, Sprague-Dawley, Solubility, Surface Properties, Technology, Pharmaceutical, Antineoplastic Agents administration & dosage, Contrast Media administration & dosage, Doxorubicin administration & dosage, Drug Carriers, Lactic Acid chemistry, Polymers chemistry, Ultrasonics, Ultrasonography, Doppler, Pulsed
- Abstract
An echogenic, intravenous drug delivery platform is proposed in which an encapsulated chemotherapeutic can travel to a desired location and drug delivery can be triggered using external, focused ultrasound at the area of interest. Three methods of loading poly(lactic acid) (PLA) shelled ultrasound contrast agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency, in vitro enhancement, stability, particle size, morphology and release during UCA rupture are compared by loading method and drug concentration. An agent containing doxorubicin within the shell was selected as an ideal candidate for future hepatocellular carcinoma studies. The agent achieved a maximal drug load of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth surface morphology and tight size distribution (poly dispersity index=0.309) with a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in vitro at a dosage of 10 microg/ml, with a half life of over 15 min. In vivo, the agent provided ultrasound enhancement of 13.4+/-1.6 dB within the ascending aorta of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent is thought to be well suited for future drug delivery experiments, this study has shown that agent properties can be tailored for specific applications based on choice of drug loading method., (Copyright 2009 Elsevier B.V. All rights reserved.)
- Published
- 2010
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