Formulation of chloroaluminum phthalocyanine incorporated into PS-b-PAA diblock copolymer nanomicelles

Abstract Chloroaluminum phthalocyanine (ClAlPc) is considered to be an important photosensitizer compound, and it has been extensively explored in photodynamic therapy (PDT) against several types of cancer cell lines. However, ClAlPc is known to be a highly hydrophobic compound. Thus, it requires physical association with a drug delivery system for clinical use. In this study, distinct formulations of PS 70.5 -b-PAA 13 diblock copolymer nanostructures containing ClAlPc were studied. Results found in this study showed that the ClAlPc/PS 70.5 -b-PAA 13 diblock composite presented micellar morphology and a size of 200 nm while dispersed in aqueous media. Additionally, zeta potential studies revealed that such formulations presented colloidal stability with low polydispersity index (PDI) values (0.121). The encapsulation efficiency of ClAlPc by such copolymer micelles, made through spectroscopic measures, was higher than 95% while at the phthalocyanine concentration range from 9.0 to 70 μmol L −1 . Spectroscopic studies also showed that the existence of monomeric ClAlPc in such nanostructured micelles is closely dependent on the PS concentration. Low PS concentration resulted in monomeric ClAlPc, as observed from the correspondent absorption and emission spectra of freshly-prepared composite. However, even after 15 days of storage and at low PS concentration, the ClAlPc can self-aggregate within the polymer-micellar nanoenvironment (as observed through spectroscopic studies). Photophysical properties of ClAlPc incorporated in the PS-b-PAA copolymer system revealed promising values of oxygen singlet generation (Φ Δ 1 O 2  = 0.3). Skin permeation studies performed by photoacoustic spectroscopy showed that the ClAlPc/PS-b-PAA nanosystem permeates and reaches the superficial dermis layer. In vitro tests, using Caco-2 cell-lines incubated with ClAlPc/PS-b-PAA formulations at different phthalocyanine concentrations, showed cellular damage after 30 min under light radiation (663 nm with LED, fluence of 1.62 μJ cm −2 ). The IC 50 obtained for the system containing ClAlPc/PS-b-PAA was 1.74 · 10 −7  mol L −1 . Furthermore, no cytotoxicity effect was observed during cell growth tests performed using both ClAlPc/PS-b-PAA composite and pristine PS-b-PAA nanomicelles in the absence of light irradiation. These findings suggested that the PS-b-PAA diblock copolymer produced a promising nanostructured system suitable for the incorporation of the hydrophobic ClAlPc photosensitizer and for subsequent use in the PDT field.