New method for delivering a hydrophobic drug for photodynamic therapy using pure nanocrystal form of the drug.
A carrier-free method for delivery of a hydrophobic drug in its pure form, using nanocrystals (nanosized crystals), is proposed. To demonstrate this technique, nanocrystals of a hydrophobic photosensitizing anticancer drug, 2-devinyl-2-(1-hexyloxyethyl)pyropheophorbide (HPPH), have been synthesized using the reprecipitation method. The resulting drug nanocrystals were monodispersed and stable in aqueous dispersion, without the necessity of an additional stabilizer (surfactant). As shown by confocal microscopy, these pure drug nanocrystals were taken up by the cancer cells with high avidity. Though the fluorescence and photodynamic activity of the drug were substantially quenched in the form of nanocrystals in aqueous suspension, both these characteristics were recovered under in vitro and in vivo conditions. This recovery of drug activity and fluorescence is possibly due to the interaction of nanocrystals with serum albumin, resulting in conversion of the drug nanocrystals into the molecular form. This was confirmed by demonstrating similar recovery in presence of fetal bovine serum (FBS) or bovine serum albumin (BSA). Under similar treatment conditions, the HPPH in nanocrystal form or in 1% Tween-80/water formulation showed comparable in vitro and in vivo efficacy.
Baba
Koichi
K
Institute for Lasers, Photonics and Biophotonics, SUNY at Buffalo, Buffalo, NY 14260, USA.
Pudavar
Haridas E
HE
Roy
Indrajit
I
Ohulchanskyy
Tymish Y
TY
Chen
Yihui
Y
Pandey
Ravindra K
RK
Prasad
Paras N
PN
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D016503:Drug Delivery Systems / Q000379:methods*; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D051379:Mice; D018613:Microscopy, Confocal; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012995:Solubility
D017319:Photosensitizing Agents