IADR Abstract Archives
Enzyme-Responsive Nanoparticles for Targeted Delivery, Accumulation and Retention of Drugs to Inflamed Oral Tissues
Objectives: There is a lack of efficient targeted drug delivery methods for the treatment of oral tissues. Enzyme-responsive nanoparticles prepared via the assembly of peptide-polymer amphiphiles (PPA) can target through the EPR effect and aggregate in the inflamed tissues in response to upregulated matrix-metalloproteinases. Most oral pathologies are inflammation-associated, therefore PPA as targeted drug delivery vehicle may improve treatment efficacy in oral inflammatory lesions. The present study demonstrates the delivery and accumulation of PPA-based nanoparticles in the oral tissues of rats following a surgical wound.
Methods: PPA containing a hydrophilic MMP-responsive peptide block, a hydrophobic phenyl block and a Cy5.5 fluorophore were prepared and formulated into micellar nanoparticles. Tissue inflammation induction was achieved by employing a surgical wound model, in which a mid-crestal incision was performed on the maxillary alveolar ridge along the existing edentulous area between the first right molar and the incisors. Rats received PPA-based nanoparticles either by local injection in the right alveolar ridge or by tail vein IV injection. In-vivo and ex-vivo detection of fluorescence at different time points were achieved. The fluorescence intensity was measured and compared to the control rats injected with MMP-nonresponsive fluorescent PPA composed of D-amino acids (D-PPA).
Results: Following IV administration, the PPA fluorescence was diffused in the oral cavity, whereas the local administration exhibited a clear fluorescence signal along the alveolar ridge. PPA accumulated preferentially in the wounded hemi-maxilla compared to D-PPA-treated and to injected un-wounded rats. Four weeks post local administration, PPA-treated rats fluorescence signal was doubled compared to D-PPA treatment. Hence, PPA demonstrates inflammation-induced aggregation and sustained accumulation capacities.
Conclusions: This study demonstrates the potential use of PPA-based nanoparticles as a targeted drug delivery method for the treatment of inflamed oral tissues. Future research is necessary to assess the possible therapeutic applications of drugs conjugated to PPA targeted to diseased oral tissues.
Methods: PPA containing a hydrophilic MMP-responsive peptide block, a hydrophobic phenyl block and a Cy5.5 fluorophore were prepared and formulated into micellar nanoparticles. Tissue inflammation induction was achieved by employing a surgical wound model, in which a mid-crestal incision was performed on the maxillary alveolar ridge along the existing edentulous area between the first right molar and the incisors. Rats received PPA-based nanoparticles either by local injection in the right alveolar ridge or by tail vein IV injection. In-vivo and ex-vivo detection of fluorescence at different time points were achieved. The fluorescence intensity was measured and compared to the control rats injected with MMP-nonresponsive fluorescent PPA composed of D-amino acids (D-PPA).
Results: Following IV administration, the PPA fluorescence was diffused in the oral cavity, whereas the local administration exhibited a clear fluorescence signal along the alveolar ridge. PPA accumulated preferentially in the wounded hemi-maxilla compared to D-PPA-treated and to injected un-wounded rats. Four weeks post local administration, PPA-treated rats fluorescence signal was doubled compared to D-PPA treatment. Hence, PPA demonstrates inflammation-induced aggregation and sustained accumulation capacities.
Conclusions: This study demonstrates the potential use of PPA-based nanoparticles as a targeted drug delivery method for the treatment of inflamed oral tissues. Future research is necessary to assess the possible therapeutic applications of drugs conjugated to PPA targeted to diseased oral tissues.