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

Citation

Kwok, C. S.; Mourad, P. D.; Crum, L. A.; & Ratner, B. D. (2001). Self-assembled molecular structures as ultrasonically-responsive barrier membranes for pulsatile drug delivery. Journal of biomedical materials research, 57(2), 151-164.

Abstract

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.

Keyword(s)

Adipocytes
Animals
Anti-Infective Agents
Cell Line
Ciprofloxacin
Deoxyglucose
Drug Carriers
Drug Delivery Systems
Humans
Hydrocarbons
Hydrogels
Insulin
Methane
Mice
Polymers
Spectroscopy, Fourier Transform Infrared
Time Factors
Ultrasonics

Reference Type

Journal Article

Secondary Title

Journal of biomedical materials research

Author(s)

Kwok, C. S.
Mourad, P. D.
Crum, L. A.
Ratner, B. D.

Year Published

2001

Volume Number

Issue Number

Pages

151-164