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AAPS PharmSciTech ; 20(6): 225, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31214798


The vaginal mucosa is a very promising route for drug administration due to its high permeability and the possibility to bypass first pass metabolism; however, current vaginal dosage forms present low retention times due to their dilution in vaginal fluids, which hampers the efficacy of many pharmacological treatments. In order to overcome these problems, this study proposes to develop a mucoadhesive in situ gelling liquid crystalline precursor system composed of 30% of oleic acid and cholesterol (7:1), 40% of ethoxylated and propoxylated cetyl alcohol, and 30% of a dispersion of 16% Poloxamer 407. The effect of the dilution with simulated vaginal fluid (SVF) on this system was evaluated by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological studies, texture profile analysis (TPA), mucoadhesion study, in vitro drug release test using hypericin (HYP) as drug model, and cytotoxicity assay. PLM and SAXS confirmed the formation of an isotropic system. After the addition of three different concentrations of SVF (30, 50, and 100%), the resultant formulations presented anisotropy and characteristics of viscous lamellar phases. Rheology shows that formulations with SVF behaved as a non-Newtonian fluid with suitable shear thinning for vaginal application. TPA and mucoadhesion assays indicated the formation of long-range ordered systems as the amount of SVF increases which may assist in the fixation of the formulation on the vaginal mucosa. The formulations were able to control about 75% of the released HYP demonstrating a sustained release profile. Finally, all formulations acted as safe vaginal drug delivery systems.

Administração Intravaginal , Géis/metabolismo , Membrana Mucosa/metabolismo , Animais , Líquidos Corporais , Cristalização , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Poloxâmero/metabolismo , Reologia , Espalhamento a Baixo Ângulo , Vagina , Viscosidade , Difração de Raios X
Photodiagnosis Photodyn Ther ; 25: 43-49, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30399457


OBJECTIVE: To evaluate the effect of antimicrobial photodynamic therapy (aPDT) using the photosensitizer hypericin-glucamine in the progression of experimentally induced periodontal disease (PD) in rats. MATERIAL AND METHODS: Subgingival ligatures were inserted around the upper second molars of 30 rats. After 7 days (Baseline), the animals were randomly distributed into 3 experimental (n = 5) groups: Hypericin-glucamine; LED (amber LED, 700 mA, 590 nm, 90 mW, 34.10 J/cm2); and aPDT (Hypericin-glucamine + LED). The treated hemimaxillae were randomly chosen. The periodontal disease progression was monitored without treatment interference in the opposite hemimaxillaes, which were used as the negative control of each animal. The euthanasia was programmed according to each experimental period, 7 or 15 days after the Baseline. Microtomographic, histometric and Tartrate Resistant Acid Phosphatase (TRAP) immunohistochemistry analyses were carried out. RESULTS: Computerized microtomography analyses indicated that the aPDT group had a significantly higher percentage of bone tissue when compared to the other 7 days experimental groups. This result was corroborated by the histometric evaluations of the furcal area. The LED-treated group presented the highest percentages of bone volume for the 15 days experimental groups, which is remarkably higher than the groups treated with Hy-g and aPDT. The histometric analyses demonstrated the control groups had greater bone loss in the proximal regions when compared to the treated groups. The aPDT led to a lower osteoclast activity at both 7 and 15 days. Thus, we can conclude that aPDT exhibits positive effects in PD treatment by promoting favorable conditions for periodontal repair.

Doenças Periodontais/tratamento farmacológico , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Masculino , Maxila/efeitos dos fármacos , Dente Molar/efeitos dos fármacos , Perileno/farmacologia , Distribuição Aleatória , Ratos , Tomografia Computadorizada por Raios X
Chem Biol Drug Des ; 91(2): 588-596, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29044929


Antimicrobial peptides are considered promising drug candidates due to their broad range of activity. VmCT1 (Phe-Leu-Gly-Ala-Leu-Trp-Asn-Val-Ala-Lys-Ser-Val-Phe-NH2 ) is an α-helical antimicrobial peptide that was obtained from the Vaejovis mexicanus smithi scorpion venom. Some of its analogs showed to be as antimicrobial as the wild type, and they were designed for understanding the influence of physiochemical parameters on antimicrobial and hemolytic activity. Some cationic antimicrobial peptides exhibit anticancer activity so VmCT1 analogs were tested to verify the anticancer activity of this family of peptides. The analogs were synthesized, purified, characterized, and the conformational studies were performed. The anticancer activity was assessed against MCF-7 mammary cancer cells. The results indicated that [Glu]7 -VmCT1-NH2 , [Lys]3 -VmCT1-NH2 , and [Lys]7 -VmCT1-NH2 analogs presented moderated helical tendency (0.23-0.61) and tendency of anticancer activity at 25 µmol/L in 24 hr of experiment; and [Trp]9 -VmCT1-NH2 analog that presented low helical tendency and moderated anticancer activity at 50 µmol/L. These results demonstrated that single substitutions on VmCT1 led to different physicochemical features and could assist on the understanding of anticancer activity of this peptide family.

Peptídeos Catiônicos Antimicrobianos/química , Antineoplásicos/química , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Humanos , Células MCF-7 , Microscopia de Força Atômica , Escorpiões/metabolismo
J Photochem Photobiol B ; 175: 89-98, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28865319


In this work we present a comparative in vitro study of photodynamic activity between hypericin (HYP) and some hypericinates (hypericin ionic pair with lysine or N-methylglucamine) in human mammary adenocarcinoma cells (MCF-7). The toxicity and phototoxicity of hypericin and hypericinates were compared, as well as their cellular uptake and localization and mutagenic, genotoxic and clonogenic capacity. Our results demonstrate that different cationic moieties promote differences in the hypericinate solubility in a biological environment, and can influence the cellular localization and the phototoxicity of the photosensitizer. It was verified that hypericinates have better efficiency to generate singlet oxygen than HYP, and a lower aggregation in biological medium. In vitro assays have shown that HYP and the hypericinates are able to permeate the MCF-7 cell membrane and accumulated in organelles near the nucleus. The difference in location, however, was not determinant to the cell death mechanism, and a higher prevalence of apoptosis for all studied compounds occurred. The photodynamic studies indicated that hypericinates were more effective than HYP and were able to inhibit the formation of cellular colonies, suggesting a possible ability to prevent the recurrence of tumors. It also appears that all compounds have relative safety for mutagenicity and genotoxicity, which opens up a further safe route for application in in vivo studies.

Perileno/análogos & derivados , Fármacos Fotossensibilizantes/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Luz , Células MCF-7 , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Perileno/química , Perileno/metabolismo , Perileno/farmacologia , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo