Self-assembled molecular structures as ultrasonically-responsive barrier membranes for pulsatile drug delivery

• Published in: Journal of biomedical materials research 2001-11, Vol.57 (2), p.151-164
• Main Authors: Kwok, Connie S., Mourad, Pierre D., Crum, Lawrence A., Ratner, Buddy D.
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Animals; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacokinetics; Biological and medical sciences; Cell Line; Ciprofloxacin - chemistry; Ciprofloxacin - pharmacokinetics; Deoxyglucose - metabolism; Drug Carriers; drug delivery; Drug Delivery Systems - methods; General pharmacology; Humans; Hydrocarbons; Hydrogels - chemistry; insulin; Insulin - chemistry; Insulin - pharmacokinetics; Medical sciences; Methane - analogs & derivatives; Methane - chemistry; Mice; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; polymeric surfaces; Polymers - chemistry; self-assembled molecular structures; Spectroscopy, Fourier Transform Infrared; surface characterization; surface modification; Time Factors; Ultrasonics; ultrasound
• ISSN: 0021-9304; 1097-4636
• DOI: 10.1002/1097-4636(200111)57:2<151::AID-JBM1154>3.0.CO;2-5

Noninvasive ultrasound has been shown to increase the release rate on demand from drug delivery systems; however, such systems generally suffer from background drug leaching. To address this issue, a drug‐containing polymeric monolith coated with a novel ultrasound‐responsive coating was developed. A self‐assembled molecular structure coating based on relatively impermeable, ordered methylene chains forms an ultrasound‐activated “on‐off switch” in controlling drug release on demand, while keeping the drug inside the polymer carrier in the absence of ultrasound. The orderly structure and molecular orientation of these C12 n‐alkyl methylene chains on polymeric surfaces resemble self‐assembled monolayers on gold. Their preparation and characterization have been published recently (Kwok et al. Biomacromolecules 2000;1(1):139–148). Ultrasound release studies showed that a copolymer of 2‐hydroxyethyl methacrylate and ethylene glycol dimethacrylate (MW 400) coated with such an ultrasound‐responsive membrane maintained sufficient insulin for multiple insulin delivery, compared with a substantial burst release during the first 2 h from uncoated samples. With appropriate surface coating coverage, the background leach rate can be precisely controlled. The biological activity of the insulin releasate was tested by assessing its ability to regulate [C14]‐deoxyglucose uptake in 3T3‐L1 adipocyte cells in a controlled cell culture environment. Uptake triggered by released insulin was comparable to that of the positive insulin control. The data demonstrate that the released insulin remains active even after the insulin had been exposed to matrix synthesis and the methylene chain coating process. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res 57: 151–164, 2001