Objectives/hypothesis

The potential utility of direct injection of bioactive substances in the treatment of vocal fold tissue fibrosis is limited by rapid clearance from the injection site. The objective of this study is to evaluate the potential of a lipid-based microtube delivery system to preserve the biological activity of injected substances and prolong their duration of pharmacological effects in the larynx.

Study design

Prospective in vitro and case-control in vivo murine study

Methods

Lipid-based microtubes were loaded with Texas red-dextran (MT-TR) and hepatocyte growth factor (MT-HGF). In vitro and in vivo (using a murine vocal fold injection model) release of MT-TR and MT-HGF were determined to assess duration of microtube-mediated delivery. The biologic effects of MT-HGF on fibroblasts were assessed after treatment in the presence of transforming growth factor (TGF)-β.

Results

In vitro release kinetics demonstrated slow release of MT-TR and MT-HGF, correlating with in vivo results demonstrating persistence of MT-HGF at 4 weeks postinjection. Bioefficacy was maintained, as MT-HGF was shown to inhibit TGF-β-mediated induction of procollagen mRNA levels in vitro 24 hours after treatment in fibroblast cells. Sustained release of HGF from microtubes at 6 days exacerbated the effects of TGF-β and increased levels of procollagen mRNA.

Conclusions

Microtubes have significant potential utility as an efficacious means of sustained-release delivery of bioactive agents to the larynx. Atthough the role of HGF as an antifibrotic agent is questioned, its sustained bioefficacy after microtube encapsulation distinguishes microtubes from other delivery vehicles.