Peptide-induced inflammatory increase in vascular permeability improves photosensitizer delivery and intersubject photodynamic treatment efficacy.
Photodynamic therapy (PDT) treatment can exhibit high intersubject variability due to the inherent differences in drug delivery within the tissue to be treated. In this study, the increased perfusion of the lipid-associated photosensitizer verteporfin was studied using substance P, a peptide known to increase vascular permeability. The transvascular permeability coefficient was quantified before and after administration of substance P, and the mean value increased from 0.026 to 0.043 microm/s with the induced inflammation. Correspondingly, there was a 40-50% increase in uptake of verteporfin in the tumor parenchyma in tumors injected with substance P compared to those without. This increased drug uptake resulted in a modest increase in tumor doubling time from 4 days with regular PDT to 6.2 days with substance P and PDT. There was also a significant reduction in the interindividual variability in with substance P plus PDT from 64% to 13%. The resulting treatment was therefore more effective and there was less variability in dose between subjects.
Zhou
Xiaodong
X
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
Chen
Bin
B
Hoopes
P Jack
PJ
Hasan
Tayyaba
T
Pogue
Brian W
BW
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011166:Porphyrins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013373:Substance P / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014657:Vasculitis / Q000139:chemically induced / Q000378:metabolism; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D013373:Substance P