Local, Controlled Delivery of Local Anesthetics In Vivo from Polymer - Xerogel Composites
Polymer-xerogel composite materials have been introduced to better optimize local anesthetics release kinetics for the pain management. In a previous study, it was shown that by adjusting various compositional and nano-structural properties of both inorganic xerogels and polymers, zero-order release kinetics over 7 days can be achieved in vitro. In this study, in vitro release properties are confirmed in vivo using a model that tests for actual functionality of the released local anesthetics.
Composite materials made with tyrosine-polyethylene glycol(PEG)-derived poly(ether carbonate) copolymers and silica-based sol–gel (xerogel) were synthesized. The in vivo release from the composite controlled release materials was demonstrated by local anesthetics delivery in a rat incisional pain model.
The tactile allodynia resulting from incision was significantly attenuated in rats receiving drug-containing composites compared with the control and sham groups for the duration during which natural healing had not yet taken place. The concentration of drug (bupivacaine) in blood is dose dependent and maintained stable up to 120 h post-surgery, the longest time point measured.
These in vivo studies show that polymer-xerogel composite materials with controlled release properties represent a promising class of controlled release materials for pain management.
KEY WORDScomposite controlled release local anesthetic sol–gel
Analysis of variance BP bupivacaine
Desaminotyrosyl tyrosine octyl ester
Fourier transform infrared spectroscopy
Gel permeation chromatography
High performance liquid chromatography
Nuclear magnetic resonance
Acknowledgments and Disclosures
This work was supported by U.S. Army contract #W81XWH-07-1-0438. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702–5014 is the awarding and administering acquisition office. The content of the manuscript does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.
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