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Pharmaceutical Research

, Volume 33, Issue 3, pp 729–738 | Cite as

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

  • Haibo Qu
  • Marius C. Costache
  • Saadet Inan
  • Alan Cowan
  • David Devore
  • Paul Ducheyne
Research Paper

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.

KEY WORDS

composite controlled release local anesthetic sol–gel 

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

Notes

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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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Haibo Qu
    • 1
  • Marius C. Costache
    • 2
  • Saadet Inan
    • 3
  • Alan Cowan
    • 3
  • David Devore
    • 4
  • Paul Ducheyne
    • 1
  1. 1.Center for Bioactive Materials and Tissue Engineering, Department of BioengineeringUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.New Jersey Center for Biomaterials, RutgersThe State University of New JerseyPiscatawayUSA
  3. 3.Department of PharmacologyTemple UniversityPhiladelphiaUSA
  4. 4.U.S. Army Institute of Surgical ResearchFort Sam HoustonUSA

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