Skeletal muscle biomechanics drives intramuscular transport of locally delivered drugs

Introduction: Effective local drug delivery to contractile tissues such as skeletal muscle requires a thorough understanding of the impact of mechanical loads on intramuscular pharmacokinetics. Current preparations for studying skeletal muscle biomechanics typically use: mounting techniques that lead to mechanical disruption of the tissue, which can create drug transport artifacts. In order to accurately study mechanical influences on drug transport, experimental techniques and setups need to meet the particular design requirements of both biomechanical testing setups and local drug delivery preparations. Studies of intramuscular pharmacokinetics require anatomically physiologic and functionally viable conditions for accurate drug transport. In this study, we invent a method for the surgical isolation and mounting of whole skeletal muscles of small rodents that maintains the physiologic configuration of the tissue. We also invent a mounting assembly and dynamic loading system designed appropriately for in vitro drug transport studies. We present an effective protocol for tissue processing and visually quantifying intramuscular distribution of drug. With the primary objective of investigating muscle pharmacokinetics, we use these techniques in a study to elucidate the influence of mechanical loading on the intramuscular transport and distribution of locally delivered drug. Methods and Results: The dynamic loading system was characterized and used to investigate intramuscular transport of aqueous macromolecular drug. The loading system was designed to achieve a maximal force, velocity, and acceleration of up to 72N, 0.45m/s, and 8.5m/s2, respectively, for imposing cyclic strain on soleus muscle samples. Total compliance of the series assembly from the motor to muscle mounting blocks was less then 0.0057 ± 0.002mm/N.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Mechanical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Wu, Peter I-Kung

Advisor dc:contributor.advisor

• Elazer R. Edelman.

• Mechanical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/42313

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/42313