Slow-release nanoparticle-encapsulated delivery system for laryngeal injection.
OBJECTIVE
There is a need for a slow-release system for local delivery of therapeutics to the larynx. Most therapeutic substances, such as steroids or chemotherapeutic agents that are injected into the larynx are cleared rapidly. Repeated laryngeal injection of these substances at short intervals is impractical. Injectable encapsulated poly(lactide-co-glycolide) (PLGA) nanoparticles offer a potential slow-release delivery system for biologically active substances in the larynx.


METHODS
Controlled animal study.


METHODS
PLGA nanoparticles were fabricated using a double emulsion method and were loaded with Texas Red-dextran (NPTR), hepatocyte growth factor (NPHGF), and bovine serum albumin (NPBSA). In vitro release of NPTR, NPBSA, and NPHGF was determined over approximately 2 weeks to assess potential duration of PLGA nanoparticle delivery. In vivo release of NPTR was assessed in a murine vocal fold injection model. The transcriptional effect of NPHGF on procollagen was measured in vitro to assess whether released growth factor retained functionality.


RESULTS
In vitro release kinetics demonstrated slow release of NPTR, NPBSA, and NPHGF over 12 to 14 days. In vitro NPTR release correlated with in vivo results. In vivo presence of NPTR occurred up to 7 days compared to 1 day for Texas Red control. In addition, NPHGF ameliorated transforming growth factor-beta induced procollagen in vitro in 3T3 fibroblast cells.


CONCLUSIONS
The results demonstrate the potential utility of nanoparticle encapsulation as an effective method for long-term delivery of specific drugs and biologically active substances to the larynx.
Kolachala
Vasantha L
VL
Emory Voice Center, Department of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Henriquez
Oswaldo A
OA
Shams
Samantha
S
Golub
Justin S
JS
Kim
Young-tae
YT
Laroui
Hamed
H
Torres-Gonzalez
Edilson
E
Brigham
Kenneth L
KL
Rojas
Mauricio
M
Bellamkonda
Ravi V
RV
Johns
Michael M
MM
D016475:3T3 Cells; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004655:Emulsions; D005347:Fibroblasts / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D007830:Larynx / Q000187:drug effects*; D008657:Metabolic Clearance Rate / Q000502:physiology; D051379:Mice; D053769:Nanocapsules; D011098:Polyglactin 910; D011347:Procollagen / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D003692:Delayed-Action Preparations; D004655:Emulsions; D053769:Nanocapsules; D011347:Procollagen; D011098:Polyglactin 910; D017228:Hepatocyte Growth Factor