Photodynamic ultradeformable liposomes: Design and characterization.

Area of Science:

• Materials Science
• Nanotechnology
• Photochemistry

Background:

• Phthalocyanines (Pc) are promising photosensitizers but often suffer from poor solubility and aggregation.
• Ultradeformable liposomes (UDL) offer a potential strategy to improve drug delivery and stability.
• Encapsulating Pcs in UDL could enhance their photodynamic therapy (PDT) efficacy.

Purpose of the Study:

• To synthesize and characterize hydrophobic (ZnPc) and hydrophilic (ZnPcMet) phthalocyanines.
• To load these phthalocyanines into ultradeformable liposomes (UDL).
• To evaluate the physicochemical properties, stability, and photodynamic activity of the UDL-encapsulated phthalocyanines.

Main Methods:

• Synthesis of hydrophobic ZnPc and hydrophilic ZnPcMet.
• Encapsulation of ZnPc and ZnPcMet into UDL composed of soybean phosphatidylcholine and sodium cholate.
• Characterization of vesicle size, Zeta potential, encapsulation efficiency, and phase transition enthalpy.
• Assessment of matrix elasticity and content leakage through nanoporous barriers.
• Measurement of singlet oxygen quantum yield (Phi(Delta)) in aqueous media.
• Cytotoxicity assays (MTT) on Vero and J-774 cells under dark and irradiated conditions.
• Evaluation of endo-lysosomal confinement using HPTS dye.

Main Results:

• UDL vesicles (100 nm, negative Zeta potential) were formed with high encapsulation efficiencies (85% for ZnPc, 53% for ZnPcMet).
• UDL-phthalocyanines exhibited significantly enhanced matrix elasticity and reduced content leakage compared to non-UDL.
• UDL-ZnPc improved aqueous solubility and maintained monomeric state, retaining high singlet oxygen yield (0.61).
• UDL-ZnPcMet showed a four-fold increase in singlet oxygen yield (0.21) compared to free ZnPcMet.
• Free phthalocyanines were non-toxic; only liposomal ZnPc at 10 microM showed toxicity to J-774 cells under irradiation.
• Endo-lysosomal confinement was maintained, suggesting potential for targeting intracellular pathogens.

Conclusions:

• UDL effectively encapsulate both hydrophobic and hydrophilic phthalocyanines, improving their stability and photophysical properties.
• The enhanced elasticity and reduced leakage of UDL-phthalocyanines are crucial for effective delivery.
• UDL-encapsulation significantly boosts the singlet oxygen generation of phthalocyanines, enhancing their potential as photodynamic agents.
• This formulation strategy holds promise for developing improved photodynamic therapies targeting intracellular pathogens within the endo-lysosomal system.