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Local, Controlled Delivery of Local Anesthetics In Vivo from Polymer - Xerogel Composites

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

ANOVA:

Analysis of variance BP bupivacaine

DI:

De-ionized water

DTO:

Desaminotyrosyl tyrosine octyl ester

FTIR:

Fourier transform infrared spectroscopy

GPC:

Gel permeation chromatography

HCl:

Hydrochloride acid

HPLC:

High performance liquid chromatography

MP:

Mepivacaine

NMR:

Nuclear magnetic resonance

PEG:

Polyethylene glycol

TEOS:

Tetraethoxysilane

THF:

Tetrahydrofuran

TFA:

Trifluoroacetic acid

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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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Author notes

    Authors and Affiliations

    1. Center for Bioactive Materials and Tissue Engineering, Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

      Haibo Qu & Paul Ducheyne

    2. New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA

      Marius C. Costache

    3. Department of Pharmacology, Temple University, Philadelphia, Pennsylvania, 19140, USA

      Saadet Inan & Alan Cowan

    4. U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas, 78234, USA

      David Devore

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    1. Haibo Qu
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    Correspondence to Paul Ducheyne.

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    “The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.”

    Haibo Qu and Marius C. Costache contributed equally to this work.

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    Qu, H., Costache, M.C., Inan, S. et al. Local, Controlled Delivery of Local Anesthetics In Vivo from Polymer - Xerogel Composites. Pharm Res 33, 729–738 (2016). https://doi.org/10.1007/s11095-015-1822-z

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    • DOI: https://doi.org/10.1007/s11095-015-1822-z

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