Diblock Copolymer Micelles Deliver Hydrophobic Protoporphyrin IX for Photodynamic Therapy

Abstract

Polymeric micelles are emerging as an effective drug delivery system for hydrophobic photosensitizers in photodynamic therapy (PDT). The objective of this study was to investigate the formulation of hydrophobic protoporphyrin IX (PpIX) with MePEG(5000)-b-PCL(4100) [methoxy poly (ethylene glycol)-b-poly (caprolactone)] diblock copolymers and to compare their PDT response to that of free PpIX. The photophysical and photochemical properties of the polymeric PpIX micelles were studied by measuring absorbance and fluorescence spectra, PpIX-loading efficiency and stability, the micelle particle size and morphology, as well as singlet oxygen luminescence and lifetime. The spherical micelles have a high PpIX-loading efficiency of 82.4% and a narrow size distribution with a mean diameter of 52.2 +/- 6.4 nm. The cellular uptake of PpIX in RIF-1 cells using PpIX micelles was approximately two-fold higher than that for free PpIX. Free PpIX and PpIX formulated in micelles exhibited similar subcellular localization in or around the cellular plasma membrane, as demonstrated using fluorescence microscopy. In vitro PDT results showed that the PpIX micelles have markedly increased photocytotoxicity over that with free PpIX, by nearly an order of magnitude at the highest light dose used. The micelles alone had no evident phototoxicity or dark toxicity. These findings suggest that MePEG(5000)-b-PCL(4100) diblock copolymer micelles have great potential as a drug delivery system for hydrophobic photodynamic sensitizers.

Nanodrug applications in photodynamic therapy

“…These systems show higher intracellular accumulation of the drug and higher photocytotoxicity in comparison to free PpIX [55]. Similar results were reported for phthalocyanines [96,97].…”

“…PS can be modified by encapsulated them in delivery agents such as liposomes [54], micelles [55,56,57,58], ceramic based nanoparticles [59], gold nanoparticles [60,61], and polymer nanoparticles [62]. Liposomes, for example, are able to encapsulate hydrophobic as well as hydrophilic drugs.…”

“…Examples of encapsulation of hydrophobic photosensitizers into nanomaterials are polymeric nanoparticles [88], e.g., a hydrophobic photosensitizer meso-tetra(phydroxyphenyl)porphyrin (m-THPP) encapsulated into polymeric nanoparticle poly(D,Llactide-co-glycolide) [89,90], dendrimer phthalocyanine (DPc)-encapsulated polymeric micelles (DPc/m) [32], polymeric protoporphyrin IX micelles [55], and organically modified silica-based nanoparticles [91] entrapping the photosensitizing anti-cancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide [59] have been used.…”

Polymeric micelles: authoritative aspects for drug delivery

“…Aggregated structures possess low quantum yields of light absorption and cause significantly less singlet oxygen production. Li et al investigated the formulation of hydrophobic protoporphyrin IX (PpIX) with methoxy PEG-b-PCL micelles and compared their PDT response to that of free PpIX [416]. Fluorescence microscopy revealed that the subcellular localization of free PpIX and PpIX formulated in micelles was similar.…”

Doxorubicin-loaded PEG-PCL copolymer micelles enhance cytotoxicity and intracellular accumulation of doxorubicin in adriamycin-resistant tumor cells

“…19 In the current study, we obtained micelles with a particle size smaller than the reported values. 21,22 This may be attributed to longer PEG chains and the lower molecular weight of the copolymer. The diameter of micelles depends largely on the hydrophilic/hydrophobic chain ratio, and higher PEG/PCL chain ratios produce smaller micelle diameters.…”