RESUMO
Hypericin (Hyp) is considered a promising photosensitizer for Photodynamic Therapy (PDT), due to its high hydrophobicity, affinity for cell membranes, low toxicity and high photooxidation activity. In this study, Hyp photophysical properties and photodynamic activity against melanoma B16-F10 cells were optimized using DPPC liposomes (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) as a drug delivery system. This nanoparticle is used as a cell membrane biomimetic model and solubilizes hydrophobic drugs. Hyp oxygen singlet lifetime (τ) in DPPC was approximately two-fold larger than that in P-123 micelles (Pluronic™ surfactants), reflecting a more hydrophobic environment provided by the DPPC liposome. On the other hand, singlet oxygen quantum yield values (ΦΔ1O2) in DPPC and P-123 were similar; Hyp molecules were preserved as monomers. The Hyp/DPPC liposome aqueous dispersion was stable during fluorescence emission and the liposome diameter remained stable for at least five days at 30 °C. However, the liposomes collapsed after the lyophilization/rehydration process, which was resolved by adding the lyoprotectant Trehalose to the liposome dispersion before lyophilization. Cell viability of the Hyp/DPPC formulation was assessed against healthy HaCat cells and high-metastatic melanoma B16-F10 cells. Hyp incorporated into the DPPC carrier presented a higher selectivity index than the Hyp sample previously solubilized in ethanol under the illumination effect. Moreover, the IC50 was lower for Hyp in DPPC than for Hyp pre-solubilized in ethanol. These results indicate the potential of the formulation of Hyp/DPPC for future biomedical applications in PDT treatment.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/análogos & derivados , Antineoplásicos/farmacologia , Melanoma/tratamento farmacológico , Perileno/análogos & derivados , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , 1,2-Dipalmitoilfosfatidilcolina/química , Antracenos , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Composição de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Estabilidade de Medicamentos , Humanos , Hypericum/química , Lipossomos/química , Melanoma/patologia , Estrutura Molecular , Perileno/síntese química , Perileno/química , Perileno/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Células Tumorais CultivadasRESUMO
CONTEXT: Recent findings have suggested a high prevalence of vitamin D deficiency or insufficiency in fibromyalgia (FM) patients despite the lack of clinical and pathophysiological evidence. OBJECTIVE: A systematic review was conducted to examine the association between vitamin D status and FM, including the effect of vitamin D supplementation. DATA SOURCE: PubMed, LILACS, Scopus, SciELO, Cochrane, and EMBASE were searched, from January 2000 to July 2018, using the descriptors "Fibromyalgia" and "Vitamin D." STUDY SELECTION: Trials including FM patients in whom vitamin D levels were assessed were eligible for inclusion. DATA EXTRACTION: Data comprised age, gender, country, aims, bias, diagnosis criteria, cutoff point, and status of vitamin D, together with FM symptoms and vitamin D supplementation protocol. RESULTS: A total of 26 articles were selected. Most of the studies were found to present unreliable control groups and small samples. Experimental data on vitamin D supplementation indicated improvement in certain FM symptoms. CONCLUSION: Prevalence of hypovitaminosis D in the FM population and the cause-effect relationship were inconclusive. Nevertheless, vitamin D supplementation may be considered as a co-adjuvant in FM therapy.