Lipossomas contendo ácido oleico e cloro-alumínio ftalocianina: desenvolvimento, caracterização e avaliação de sua penetração cutânea in vitro associada ao microagulhamento

Abstract

Chloro-aluminum phthalocyanine (AlClPc) belongs to the second generation of photosensitizers (FS) applicable to photodynamic therapy (PDT) of skin cancer due to its high absorption coefficient in the therapeutic window of the light spectrum (600-800nm) along with the long lifetime of their excited singlet and triplet states. However, its direct administration is impossible due to the molecule's high hydrophobicity and tendency to self-aggregate in an aqueous medium. Thus, the encapsulation of FS in liposomes as well as the use of chemical and/or physical absorption promoters may represent strategies for the feasibility and optimization of its cutaneous penetration. The objective of this study was to develop liposomes based on soy phosphatidylcholine and cholesterol containing oleic acid (OA) for the delivery of AlClPc, as well as to evaluate its cutaneous penetration associated with microneedling. For the optimization of the developed formulation, the strategy of quality by design was used through Box-benhken, with three factors and three levels. As independent variables, the particle size, the encapsulation efficiency and the polydispersity index (PdI) of the liposomes were adopted. For the in vitro skin penetration tests, full thickness skin of the ears of recently slaughtered pigs and a roller with solid titanium microneedles of 0.25 mm in length were used. The developed liposomes showed particle size, encapsulation efficiency, PdI and mean zeta potential of 153.20 ±13.39 nm, 69.09 ± 3.31%, 0.309 ± 0.03 and -15.24 mV, respectively. Morphological analysis revealed spherical or nearly spherical vesicles, while DSC and FTIR analyzes suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous or molecularly dispersed state. In vitro skin penetration tests revealed that AlClPc does not show transdermal absorption, remaining retained in the epidermal and dermal layers, where skin tumors are usually found. The drug encapsulation in AOcontaining liposomes increased its penetration in the stratum corneum and in the viable epidermis + dermis by ~20 and 8-fold, respectively (p < 0.05). Microneedling promoted an additional 1.3-fold increase in drug transport to viable skin layers (p < 0.05). That said, the Box-Benhken statistical design was successful in providing an optimized liposomal formulation. Furthermore, the results obtained in this study suggest that the encapsulation of AlClPc in liposomes associated with chemical and physical absorption promoters is a promising strategy for the photodynamic therapy of skin cancer.