Thermoresponsive Hydrogel-Loading Aluminum Chloride Phthalocyanine as a Drug Release Platform for Topical Administration in Photodynamic Therapy.

Phthalocyanine aluminum chloride (Pc) is a clinically viable photosensitizer (PS) to treat skin lesions worsened by microbial infections. However, this molecule presents a high self-aggregation tendency in the biological fluid, which is an in vivo direct administration obstacle. This study proposed the use of bioadhesive and thermoresponsive hydrogels comprising triblock-type Pluronic F127 and Carbopol 934P (FCarb) as drug delivery platforms of Pc (FCarbPc)-targeting topical administration. Carbopol 934P was used to increase the F127 hydrogel adhesion on the skin. Rheological analyses showed that the Pc presented a low effect on the hydrogel matrix, changing the gelation temperature from 27.2 ± 0.1 to 28.5 ± 0.9 °C once the Pc concentration increases from zero to 1 mmol L-1. The dermatological platform showed matrix erosion effects with the release of loaded Pc micelles. The permeation studies showed the excellent potential of the FCarb platform, which allowed the partition of the PS into deeper layers of the skin. The applicability of this dermatological platform in photodynamic therapy was evaluated by the generation of reactive species which was demonstrated by chemical photodynamic efficiency assays. The low effect on cell viability and proliferation in the dark was demonstrated by in vitro assays using L929 fibroblasts. The FCarbPc fostered the inhibition of Staphylococcus aureus strain, therefore demonstrating the platform's potential in the treatment of dermatological infections of microbial nature.

Hypericin photodynamic activity in DPPC liposome. PART I: biomimetism of loading, location, interactions and thermodynamic properties.

Hypericin (Hyp) is a potential photosensitizer drug for Photodynamic Therapy (PDT). However, the high lipophilicity of Hyp prevents its preparation in water. To overcome the Hyp solubility problem, this study uses the liposomal vesicle of DPPC. Otherwise liposome is also one of the most employed artificial systems that mimetizes cell membranes. Our present focus is the interaction of Hyp into DPPC liposome as biomimetic system. We studied the loading, interaction, and localization of Hyp (2.8 µmol L-1) in DPPC (5.4 mmol L-1) liposomes, as well as the thermodynamic aspects of Hyp-liposomes. The Hyp addition to the DPPC liposome dispersion showed a Encapsulation Efficiency for [Hyp] = 2.8 µmol L-1 in [DPPC] = 5.3 mmol L-1 of 74.3% and 89.3% at 30.0 and 50.0 °C, respectively. The encapsulation profile obeys a pseudo first-order kinetic law, with a rate constant of 1.26 × 10-3 s-1 at 30.0 °C. Also the data suggests this reaction is preceded by an extremely rapid step. A study on the binding of Hyp/DPPC liposomes (Kb), performed at several temperatures, showed results of 4.8 and 18.5 × 103 L mol-1 at 293 and 323 K, respectively. Additionally, a decrease was observed in the ΔG of the Hyp/DPPC interaction (-20.6 and - 26.4 kL mol-1 at 293 and 323 K, respectively). The resulting ΔH > 0 with ΔS < 0 shows that the entropy is driven the process. Studies of Hyp location in the liposome at 298 K revealed the existence of two different Hyp populations with a Stern-Volmer constant (Ksv) of 4.65 and 1.87 L mol-1 using iodide as an aquo-suppressor at concentration ranged from 0 to 0.025 mol L-1 and from 0.025 to 0.150 mol L-1, respectively. Furthermore, studies of Fluorescence Resonance Energy Transfer, using DPH as a donor and Hyp as an acceptor, revealed that Hyp is allocated in different binding sites of the liposome. This is dependent on temperature. Thermal studies revealed that the Hyp/DPPC formulation presented reasonable stability. Size and morphological investigations showed that Hyp incorporation increases the average size of DPPC liposomes from 116 to 154 nm. The study demonstrated the ability of the Hyp-DPPC liposome as an interesting system for drug delivery system that can be applied to PDT.

Biomedical Platform Development of a Chlorophyll-Based Extract for Topic Photodynamic Therapy: Mechanical and Spectroscopic Properties.

Photodynamic therapy (PDT) is a therapeutic modality that has shown effectiveness in the inactivation of cancer cell lines and microorganisms. Treatment consists of activating the photosensitizer (PS) upon light irradiation of adequate wavelength. After reaching the excited state, the PS can handle the intersystem conversion through energy transfer to the molecular oxygen, generating reactive oxygen species. This especially applies to singlet oxygen (1O2), which is responsible for the selective destruction of the sick tissue. Photosensitizing compounds (chlorophylls and derivatives) existing in the spinach extract have applicability for PDT. This study aimed to develop and characterize the thermoresponsive bioadhesive system composed of Pluronic F127 20.0%- and Carbopol 934P 0.2% (w/w) (FC)-containing chlorophyll-based extract 0.5% (w/w) (FC-Chl). Mechanical and rheological properties, in vitro release, sol-gel transition temperature, and ex vivo permeability of the spinach extract PS components (through pig ear skin) were investigated. Furthermore, photodynamic activity of the system was accessed through uric acid and time-solved measurements. The sol-gel transition temperature obtained for the FC-Chl system was 28.8 ± 0.3 °C. Rheological and texture properties of the platform were suitable for use as a dermatological system, exhibiting easy application and good characteristics of retention in the place of administration. In vitro release studies showed the presence of two distinct mechanisms that reasonably obey the zero-order and first-order kinetics models. PS components presented skin permeability and reached a permeation depth of 830 µm (between the epidermis and dermis). The photodynamic evaluation of the FC-Chl system was effective in the degradation of uric acid. The quantum yield (ΦΔ1O2) and life time (τ1O2) of singlet oxygen showed similar values for the spinach extract and the isolated chlorophyll a species in ethanol. These results allowed for the classification of the FC-Chl platform as potentially useful for the delivery of the chlorophyll-based extract in the topic PDT, suggesting that it is worthy for in vivo evaluation.