2008 NSTI Nanotechnology Conference and Trade Show - Nanotech 2008 - 11th Annual

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Clean Technology 2008

Novel Micellular Formulations of a Polyethylene Glycolated Pyropheophorbide-a-Peptide Conjugate for Photodiagnosis and Photodynamic Therapy

M.D. Savellano
Dartmouth College, US

micelle, conjugate, polyethylene glycol, peptide, photosensitizer, fluorescence, imaging, photodiagnosis, photodynamic therapy

Many dyes used in photodiagnosis and photodynamic therapy (PDT) are hydrophobic and poorly soluble. Traditional methods of solubilizing compounds for in vivo applications have included formulating compounds in solubilizers (e.g., surfactants or liposomes) or derivatizing them with peripheral water-solubilizing groups (e.g., sulfonic acid residues). Although these approaches have had some success, they each have potentially significant drawbacks. Consequently, as an alternative, novel micellular formulations of a poorly soluble fluorescent photosensitizer dye, pyropheophorbide-a (PPa), were investigated in this study. A short linear polyethylene glycol (PEG) PPa-peptide conjugate (sPPp; sequence: N-epsilon(PPa-Asp)-Lys-PEG(11-mer)-PEG(11-mer)) was either conjugated to a 20 kDa double-branched PEG (PEG2(20kDa)) or a commercial anti-epidermal growth factor receptor (EGFR) antibody, Erbitux, to generate preparations for passive and active targeting applications, respectively. Because the sPPp construct is highly amphiphilic/amphipathic and is strongly driven to form micelles in aqueous solutions, the PEG2(20kDa)-sPPp and Erbitux-sPPp conjugates consisted of covalently conjugated sPPp as well as noncovalently-associated sPPp tightly bound via amphiphilic interactions. In fluorescence imaging and PDT studies, both the PEG2(20kDa)-sPPp and Erbitux-sPPp conjugates exhibited remarkable improvements in tumor-targeting capabilities compared to a conventional surfactant-solubilized PPa preparation. Similar novel micellular formulations could also prove useful for many other types of poorly soluble drugs.

Nanotech 2008 Conference Program Abstract