Low-intensity light-induced drug release from a dual delivery system comprising of a drug loaded liposome and a photosensitive conjugate

Abstract

This study reports the development of a binary drug delivery system consisting of charged liposomes and an oppositely charged peptide–photosensitiser conjugate. Liposomes were prepared with phosphatidyl-l-serine as a negatively charged lipid. Calcein, a fluorophore marker, and doxorubicin, an anticancer drug, were used as model hydrophilic loads. The conjugate consisted of a positively charged arginine-rich peptide synthesised by solid-phase peptide synthesis, and a phthalocyanine derivative with characteristic absorption around 685 nm. Illumination of the binary system with far-red light of 12–15 mW/cm² intensity resulted in 5- to 15-fold increase in release of payloads from the liposomes. The mechanism of drug release was based on photosensitised oxidation of lipids destabilising the liposomal membrane. The cytotoxicity of the liposomes loaded with doxorubicin was tested on B16-F10 melanoma and Y79 retinoblastoma cells. The cytotoxicity of the illuminated binary system in melanoma cell line was significantly higher as compared to the system without illumination. The components of the binary system can be individually prepared and stored with greater storage stability. However, their combination will allow for substantial release of hydrophilic payload from the liposomes under externally applied light.

Keywords:

• Controlled release
• liposomes
• doxorubicin
• far-red photosensitiser
• low-intensity light

Acknowledgements

The authors thank Dr. D. David Smith (Creighton University), for assistance with the synthesis of RLA peptide and its HPLC analysis, Daniel Munt (Creighton University), for assistance with HPLC determination of the drug release, Brad Walters (Creighton University), for manufacturing the custom parts of the illumination setups, and the personnel of Mass Spectrometry and Proteomics Core Facility of University of Nebraska, for assistance with MALDI TOF identification of the RLA peptide and its phthalocyanine conjugate.

Disclosure statement

No potential conflict of interest was reported by the authors.