Preliminary research on metalized phthalocyanines synthesis. Evaluation as potential photosensitizer in photodynamic therapy

SUMMARY Introduction: Phthalocyanines are porphyrin-based dyes. They have plenty applications in different fields, including biomedical and chemical research. From a chemical point of view, Phthalocyanines are macrocyclictetraaza compounds, which mainly are made up of isoindol groups that confer aromaticity and planarity on Phthalocyanine structure. Unlike other kinds of porphyrin compounds, Phthalocyanine structure is able to chelate a lot of metals, which more often contribute to their huge variety of functions, including ROS generation, fluorescence, absorption spectra, and others. Aim: To evaluate phthalocyanines compounds owing their excellent photochemical and pharmaceutical properties that explain their wide use at the clinical and medical level. Methodology: We have carried out a meticulous search for scientific works related to the subject between April 2020 and April 2021, the most of them were written in English. As a result, we can say that, for studying Phthalocyanines' properties, the work can be separated into two issues: synthesis of the metalized phthalocyanines and photochemical and photobiological properties. Results: Phthalocyanines have plenty properties that are desirable to biomedical and pharmaceutical research. Because of their photochemical and photobiological properties, as well as ROS generation, Phthalocyanines are one of the photosenstitizers most widely used in photodynamic therapy. They also have antibacterial, antiviral and anticancer activities. In this sense, Phthalocyanine synthesis and in vitro studies are a very important scientific issue.

Introducción: las ftalocianinas son tintes porfirínicos. Tienen muchas aplicaciones en diferentes campos, incluida la investigación biomédica y química. Desde el punto de vista químico, las ftalocianinas son compuestos macrocíclicos de tetraaza. Se componen principalmente de grupos isoindol que confieren aromaticidad y planaridad a la estructura de la ftalocianina. Esta última es capaz de quelar muchos metales, que con mayor frecuencia contribuyen a su gran variedad de funciones, incluida la generación de EROS, la fluorescencia, los espectros de absorción y otros. Objetivo: evaluar algunos derivados de ftalocianinas gracias a las excelentes propiedades fotoquímicas y farmacéuticas que explican su amplio uso a nivel clínico y médico. Metodología: hemos realizado una búsqueda minuciosa de trabajos científicos relacionados con el tema entre abril de 2020 y abril de 2021, la mayoría de ellos escritos en inglés. Como resultado, podemos decir que, para estudiar las propiedades de las ftalocianinas, el trabajo se puede dividir en dos temas: síntesis de las ftalocianinas metalizadas y propiedades fotoquímicas y ffotobiológicas. Resultados: las ftalocianinas tienen muchas propiedades que son deseables para la investigación biomédica y farmacéutica. Por sus propiedades fotoquímicas y fotobiológicas, así como por la generación de EROS, las ftalocianinas son uno de los fotosensibilizadores más utilizados en terapia fotodinámica. También tienen actividades antibacterianas, antivirales y anticancerígenas. En este sentido, la síntesis de ftalocianina y los estudios in vitro son un tema científico muy importante.

Introdução: as ftalocianinas são corantes à base de porfirinas. Eles têm muitas aplicações em diferentes campos, incluindo pesquisas biomédicas e químicas. Do ponto de vista químico, as ftalocianinas são compostos macrocíclicos tetraaza, que são constituídos principalmente por grupos isoindol que conferem aromaticidade e planaridade à estrutura das ftalocianinas. Ao contrário de outros tipos de compostos de porfirina, a estrutura da ftalocianina é capaz de quelar uma grande quantidade de metais, que mais frequentemente contribuem para sua enorme variedade de funções, incluindo geração de ROS, fluorescência, espectro de absorção e outros. Objetivo: avaliar alguns derivados de ftalocianinas graças às excelentes propriedades fotoquímicas e farmacêuticas que explicam a sua ampla utilização a nível clínico e médico. Metodologia: efetuamos uma busca minuciosa de trabalhos científicos relacionados ao assunto entre abril de 2020 e abril de 2021, a maioria deles redigidos na língua inglesa. Como resultado, podemos dizer que, para estudar as propriedades das ftalocianinas, o trabalho pode ser dividido em duas questões: síntese das ftalocianinas metalizadas e propriedades fotoquímicas e fotobiológicas. Resultados: as ftalocianinas têm muitas propriedades desejáveis para a pesquisa biomédica e farmacêutica. Pelas suas propriedades fotoquímicas e fotobiológicas, além da geração de ROS, as ftalocianinas são um dos ffotossensibilizantes mais amplamente utilizados na terapia fotodinàmica e processos fototóxicos. Eles também têm atividades antibacteriana, antiviral e anticàncer. Nesse sentido, a síntese de ftalocianina e os estudos in vitro são uma questão científica muito importante.

Effects of nanoparticles of hydroxy-aluminum phthalocyanine on markers of liver injury and glucose metabolism in diabetic mice

Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.

Transferosomas conteniendo ftalocianina de aluminio clorada como alternativa terapéutica en leishmaniasis cutánea: permeabilidad y biodistribución en ratas Wistar / Transferosomes loaded with chloroaluminum phthalocyanine as cutaneous leishmaniasis therapeutic alternative: permeability and biodistribution in Wistar rats

Resumen Objetivo: Evaluar la permeabilidad, retención y biodistribución de los LUD-PcAlCl in vivo. Metodología: Los transferosomas fueron obtenidos mediante rehidratación de película lipídica. Ratas Wistar fueron tratadas tópica e intraperitonealmente con los transferosomas por 5 días. La penetración ex vivo fue determinada mediante el ensayo en celdas de Franz y la retención por el método de la cinta adhesiva. Cinco y treinta días postratamiento se obtuvo la piel y órganos para determinar la retención del compuesto y realizar estudios histopatológicos. La PcAlCl fue extraída con solventes y cuantificada por fluorometría. Los resultados se expresaron en nM PcAlCl/mg órgano. Resultados: La PcAlCl no penetró la piel en los ensayos ex vivo, reteniéndose principalmente en el estrato córneo. Cinco días post-tratamiento tópico la PcAlCl fue retenida en estrato córneo (41,76±0,02), mostrando concentraciones mínimas en bazo (0,09±0,02), epidermis-dermis (0,06±0,17), hígado (0,03±0,02) y pulmón (0,02±0,01 nM). Por vía intraperitoneal se encontró PcAlCl en bazo (0,58±0,4), cerebro (0,07±0,07), corazón (0,07±0,12), pulmón (0,012±0,01) y piel (0,021±0,02 nM). Treinta días postratamiento no se encontró PcAlCl en ningún órgano. Los estudios histopatológicos fueron negativos. Conclusión: La PcAlCl contenida en transferosomas fue retenida principalmente en estrato córneo, mostrando bajas concentraciones en la dermis, sitio donde se aloja el parásito. Se sugiere modificar los componentes vesiculares del sistema para aumentar la permeación del compuesto.

Abstract Objective: To assess the UDL-ClAlPc permeability, retention and biodistribution in vivo. Methods: Transferosomas were obtained by lipid film re-hydration method. Wistar rats were treated topically and intraperitoneally with UDL-ClAlPc for 5 days. Skin and organs were collected five and thirty days after-treatment to determine ClAlPc retention and histopatho-logical studies. The ClAlPc was extracted with solvents and quantified by fluorometry. The results were expressed in nM PcAlCl/mg organ. The permeation was tested ex vivo using Franz-diffusion cells and the retention in stratum corneum and epidermis-dermis by tape stripping. Results: In the ex vivo experiments ClAlPc-UDL was not able to penetrate rat skin and was retained mainly in the stratum corneum. In rat, five days after topical treatment ClAlPc was retained mainly in the stratum corneum (41.76±0.02) with minimum concentrations in spleen (0.09±0.02), epidermis-dermis (0.06±0.17), liver (0.03±0.02) and lung (0.02±0.01 nM). After intra peritoneal treatment, ClAlPc was found in spleen (0.58±0.4), brain (0.07±0.07), heart (0.07±0.12), lung (0.01±0.012) and skin (0.021±0.02 nM). Thirty days post-treatment ClAlPc was not found in any organ. Histopathological studies were negative. Conclusion: The ClAlPc contained in transferosomes was retained mainly in the stratum corneum. Low concentration was detected in dermis a place where the parasite survives. This vehicle needs to be improved to increase skin penetration.

Targeting ability and photoacoustic imaging of novel nanoparticle probe loaded with ZnPc and docetaxel: An in vitro study / 中国介入影像与治疗学

Objective To investigate the targeting ability and photoacoustic imaging of novel nanoparticle probe loaded with ZnPc and docetaxel.Methods The polymeric nanoparticles probe loaded with ZnPc and docetaxel were fabricated using double emulsion method.RGDfK was modified on the surface for breast carcinoma targeting by carbodiimide method.The encapsulating ratio (ER) and drug loading (DL) of ZnPc and docetaxel were assessed.The modification rate and targeting ability of molecular probe were tested in vitro,and the photoacoustic imaging and drug release profiles were observed.Results The probes were loaded with ZnPc and docetaxel efficiently and successfully.The size of novel nanoparticle loaded with ZnPc and docetaxel was (266.00 ± 65.85)nm,and the surface potential was (-29.20± 6.27)mV.ER and DL of docetaxel was (88.00±0.32)％ and (34.92±0.02)μg/mg,of ZnPc was (97.25±0.22)％ and (30.87±0.11)μg/mg,respectively.The probes had certain sustained slow release effect and showed obvious photoacoustic signals,which enhanced with the increase of the content of ZnPc.Flow cytometry detection results showed that the RGDfk modification rate was 89.19％.The apoptotic rate of novel nanoparticle loaded with ZnPc and docetaxel targeting breast carcinoma increased after the laser irradiation in vitro.Conclusion The new polymeric multifunctional nanoparticles probe has an ideal size and good photoacoustic signals,also the ability to target breast carcinoma cells and inhibit the proliferation of breast carcinoma cells efficiently.

Influence of Extraction Methods on Oil Yield of Celery Seeds and Contents of 3-n-butylphthalide and Total Phthalocyanine Lactones in Celery Seed Oil / 广州中医药大学学报

Objective To compare the oil yield of celery seeds and the contents of 3-n-butylphthalide and the total phthalocyanine lactones of celery seed oil extracted by different methods. Methods Three routine extraction methods involving organic solvent extraction, Soxhlet extraction, steam distillation extraction, as well as subcritical extraction method and supercritical fluid extraction method were used to extract the celery seed oil. The contents of 3-n-butylphthalide and total phthalocyanine lactones were respectively detected by high performance liquid chromatography(HPLC) and ultraviolet visible spectrophotometry. Results The ranges of oil yield and the contents of 3-n-butylphthalide and total phthalocyanine lactones of celery seed oil extracted by different methods were 0.30%-20.02%, 1.40%-10.13%, 4.74%-17.65%, respectively, indicating obvious differences. Conclusion With R134a and butane as the solvents, the subcritical extraction method is better than other extraction methods for the extraction of 3-n-butylphthalide. With dimethyl ether as the solvent, the subcritical extraction method is the best for the extraction of total phthalocyanine lactones.

Permeación en piel humana de una nanoemulsión de ftalocianina de aluminio clorada para la optimización de tratamientos tópicos de leishmaniasis cutánea / Human Skin Permeation of a Chloroaluminum Phthalocyanine Nanoemulsion for Optimization of Topical Cutaneous Leishmaniasis Formulations / Permeação em pele humana de uma nanoemulsão de ftalocianina de alumínio clorada para a otimização de tratamentos tópicos de leishmaniose cutânea

Introducción: Las nanoemulsiones son excelentes sistemas de transporte y entrega de fármacos. La ftalocianina de aluminio clorada (PcAlCl) en terapia fotodinámica constituye una alternativa de tratamiento en leishmaniasis cutánea. Objetivo: Determinar la difusión y retención en piel humana de la PcAlCl contenida en una nanoemulsión (nano-PcAlCl) para su optimización en formulaciones tópicas. Materiales y métodos: Se prepararon y caracterizaron fisico-químicamente dos formulaciones (nano-PcAlCl y solución-PcAlCl) y sus vehículos sin-PcAlCl. La permeación se determinó en ensayos en celdas de difusión de Franz y la retención por el método de la cinta adhesiva. La concentración de PcAlCl fue determinada fluorométricamente (nM/cm2). Biopsias de piel fueron analizadas histotécnicamente. Resultados: El tamaño promedio, el potencial Z y el índice de polidispersión de la nano-PcAlCl en agua fue de 132,9 nm, -19,23 y 0,14 y diluida en PBS fue 125,33 nm, -13,69 y 0,139. Las concentraciones de PcAlCl se mantuvieron estables. La PcAlCl no atravesó la piel y fue retenida en sus capas, en estrato córneo y epidermis+dermis con valores de 44,17 nM y 8,48 nM postratamiento con nano-PcAlCl, y 96,90 nM y 9,80 nM postratamiento con solución-PcAlCl. Esta última promovió mayor retención en estrato córneo y ambas formulaciones promovieron similar retención en epidermis+dermis. Se observó desprendimiento del estrato córneo y fragmentación del colágeno. Conclusión: La PcAlCl no atravesó la piel, se retuvo en estrato córneo y epidermis+dermis. Se sugiere realizar ensayos de permeación utilizando piel humana desprovista de estrato córneo y ensayos de distribución en animales con leishmaniasis cutánea.

Introduction: The nanoemulsions constitute excellent drug delivery systems for carrying and delivering active drugs. Chloroaluminum phthalocyanine (ClAlPc) in photodynamic therapy constitutes an interesting alternative in cutaneous leishmaniasis treatment. Objective: To determine the diffusion and retention of ClAlPc contained in a nanoemulsion (nano-ClAlPc) in human skin membranes for optimization of topical formulations. Materials and methods: Two formulations (ClAlPc-nano- and ClAlPc-solution) and vehicles without ClAlPc were prepared and physicochemical characterized. The permeation was tested in Franz-diffusion cells and the retention by the tape stripping method. ClAlPc concentration was determined fluorometrically (nM/cm2). Skin biopsies were analyzed by histologic technics. Results: The ClAlPc-nano average size, zeta potential and polydispersity index diluted in water was 132.9 nm, -19.23 and 0.14 and diluted in phosphate-buffer-saline was 25.33 nm, -13.69 and 0.139. ClAlPc maintains its stability in each formulation. ClAlPc was unable to pass completely through the skin; it was retained in the different skin layers. A ClAlPc retention in stratum corneum and epidermis+dermis was observed with values of 44.17 nM and 8.48 nM after ClAlPc-nano treatment and 96.90 nM and 9.80 nM after ClAlPc-solution treatment. The ClAlPc-solution promoted greater retention in stratum corneum and both formulations showed similar ClAlPc-retention in epidermis+dermis. Histological changes as stratum corneum detachment and collagen-fragmentation were observed. Conclusion: ClAlPc was not able to cross completely the skin, it was retained in stratum corneum and epidermis+dermis Human permeation test using skin membranes without stratum corneum, and distribution assays in cutaneous leishmaniasis-infected animals, are suggested.

Introdução: as nanoemulsões são excelentes sistemas de transporte e entrega de fármacos. A ftalocianina de alumínio clorada (PcAlCl) em terapia fotodinâmica constitui uma alternativa de tratamento em leishmaniose cutânea. Objetivo: determinar a difusão e retenção em pele humana da PcAlCl contida em uma nanoemulsão (nano-PcAlCl) para sua otimização em formulações tópicas. Materiais e métodos: se prepararam e caracterizaram fisico-quimicamente duas formulações (nano-PcAlCl e solução-PcAlCl) e seus veículos sem-PcAlCl. A permeação determinou-se em ensaios em celas de difusão de Franz e a retenção pelo método da fita adesiva. A concentração de PcAlCl foi determinada fluorometricamente (nM/cm²). Biopsias de pele foram analisadas histotecnicamente. Resultados: o tamanho médio, o potencial Z e o índice de polidispersão da nano-PcAlCl em água foi de 132,9 nm, -19,23 e 0,14 e diluída em PBS foi 125,33 nm, -13,69 e 0,139. As concentrações de PcAlCl mantiveram-se estáveis. A PcAlCl não atravessou a pele, foi retido em suas capas. A PcAlCl foi retida em estrato córneo e epiderme+derme com valores de 44,17 nM e 8,48 nM pós-tratamento com nano-PcAlCl e 96,90 nM e 9,80 nM pós-tratamento com solução-PcAlCl. A solução-PcAlCl promoveu maior retenção em estrato córneo e ambas as formulações promoveram similar retenção em epiderme+derme. Observou-se desprendimento do estrato córneo e fragmentação do colágeno. Conclusão: a PcAlCl não atravessou a pele; reteve-se em estrato córneo e epiderme+derme. Sugere-se realizar ensaios de permeação utilizando pele humana desprovida de estrato córneo e ensaios de distribuição em animais com leishmaniose cutânea.

Novel Method for Determination of Lysozyme Based on Fluorescence Recovery of a Cationic Aluminum Phthalocyanine-Mucopolysaccharides Association Complex Used as a Red Emitting Fluorogenic Substrate / 分析化学

We developed a novel method for the rapid determination of lysozyme using a new fluorogenic substrate that consists of a cationic aluminum phthalocyanine ( tetra ( trimethylammonio ) aluminum phthalocyanine, TTMAAlPc ) , and an anionic mucopolysaccharide ( heparin, HP ) . We found that fluorescence from the cationic aluminum phthalocyanine, a red-region fluorescence probe, was quenched significantly in acidic media in the presence of low concentrations of anionic mucopolysaccharide heparin ( HP) bearing anionic sulfonic acid groups, because of induced aggregation. The practically non-fluorescent substrate degraded into small molecular fragments upon the hydrolysis of lysozyme, and thus the phthalocyanine molecules aggregated in HP were released, resulting in significant fluorescence recovery in the reaction system. This phenomenon forms the foundation of the proposed method. The reaction mechanism was determined using fluorescence spectroscopy and fluorescence anisotropy techniques. Factors that affected the determination were investigated. Under optimal conditions, the linear range was 0. 2-2 mg/L, and the detection limit was 0. 015 mg/L. The developed method is easy to operate and has good selectivity and sensitivity. This method was used in the analysis of practical samples of lysozyme, and the results were in agreement with those determined by a conventional turbidimetric method.

Determination of chondroitin sulfate with high sensitivity by fluorescence recovery through shifting the equilibrium between anionic phthalocyanine and cationic surfactant / 中国药学杂志

OBJECTIVE: To propose a novel method for quantitative determination of chondroitin sulfate in real samples using the ion-association phthalocyanine complex as a fluorescent probe emitting at red-region. METHODS: The fluorescence of tetrasulpnonat-ed aluminum phthalocyanine (AlS4Pc), an anionic metal phthalocyanine, was quenched dramatically by cationic surfactants which contain a positively-charged head with a conjugated structure and a long carbon chain as tail through the formation of an almost non-fluorescent association complex. Hexadecylpyridinium bromide (CPB) screened from a series of cationic surfactants was selected as a quencher because of its high fluorescence quenching efficiency. It was found that the ion-association complex (AlS4Pc-CPB) emitted strong fluorescence in the presence of chondroitin sulfate, due to the ability of chondroitin sulfate to shift the association equilibrium of the ion-association complex, which led to the release of AlS4Pc, thus resulting in an increase in the fluorescence of AlS4Pc. The method based on the above-mentioned phenomenon was investigated in the aspects of spectral characteristics, effect of pH, influence of reaction time, order of addition of reagents, the usage of reagents, and interference of foreign substances. RESULTS: Under optimal conditions, the linear range of the assay for chondroitin sulfate was 0.2-6 μg·mL-1 with a detection limit of 0.09 μg·mL-1. CONCLUSOIN: The established method is not only sensitive, accurate but also simple and reliable. It has been used to the analysis of real samples with complicated composition with satisfactory results. It has also been successfully applied in batch test combined with well-reader technique, exhibiting great potential for high-throughput analysis.

Protein microarray for complex apoptosis monitoring of dysplastic oral keratinocytes in experimental photodynamic therapy

BACKGROUND: Photodynamic therapy is an alternative treatment of muco-cutaneous tumors that uses a light source able to photoactivate a chemical compound that acts as a photosensitizer. The phthalocyanines append to a wide chemical class that encompasses a large range of compounds; out of them aluminium-substituted disulphonated phthalocyanine possesses a good photosensitizing potential. RESULTS: The destructive effects of PDT with aluminium-substituted disulphonated phthalocyanine are achieved by induction of apoptosis in tumoral cells as assessed by flow cytometry analysis. Using protein microarray we evaluate the possible molecular pathways by which photodynamic therapy activates apoptosis in dysplastic oral keratinocytes cells, leading to the tumoral cells destruction. Among assessed analytes, Bcl-2, P70S6K kinase, Raf-1 and Bad proteins represent the apoptosis related biomolecules that showed expression variations with the greatest amplitude. CONCLUSIONS: Up to date, the intimate molecular apoptotic mechanisms activated by photodynamic therapy with this type of phthalocyanine in dysplastic human oral keratinocytes are not completely elucidated. With protein microarray as high-throughput proteomic approach a better understanding of the manner in which photodynamic therapy leads to tumoral cell destruction can be obtained, by depicting apoptotic molecules that can be potentially triggered in future anti-tumoral therapies.

Permeación en piel y biodistribución de una nanoemulsión de ftalocianina de aluminio clorada (PcAlCl) aplicada tópicamente en ratas Wistar / Skin permeation and biodistribution of chloroaluminum phthalocyanine (ClAlPc) nanoemulsion applied topically in Wistar rats

Una formulación tópica en leishmaniasis cutánea debe garantizar la permeación y acumulación del compuesto en la dermis, sitio donde se encuentran los macrófagos infectados con Leishmania. Se determinó la difusión y retención de PcAlCl contenida en una nanoemulsión (nano-PcAlCl) y en solución-PcAlCl y su distribución en ratas Wistar, con piel sana o lesionada quirúrgicamente. La nano-PcAlCl se preparó por el método de emulsificación espontánea y la solución-PcAlCl en mezcla DMSO: Tween 80: agua tipoI; la estabilidad se determinó espectrofotométricamente. La difusión se determinó utilizando celdas de Franz y la retención en el estrato córneo (EC) y la epidermis-dermis (E+D) por "tape stripping". Las formulaciones mantuvieron las características espectroscópicas del compuesto. La PcAlCl no difundió al medio receptor. Después de 12 y 24 horas la retención del compuesto en EC con nano-PcAlCl fue 99,73 y 79,40nM y con solución-PcAlCl 66,73 y 57,01nM; en E+D la retención con nano-PcAlCl fue 40,94 y 62,49nM y con solución-PcAlCl 81,92 y 50,28nM. En EC la nano-PcAlCl registró mayor retención y en E+D la solución-PcAlCl, registró mayor retención a las 12 horas y la nano-PcAlCl a las 24 horas. Se observó desprendimiento y disminución en las capas del epitelio. El tratamiento con nano-PcAlCl retuvo el compuesto en EC y E+D de los animales con valores de 6,43nM y 33,18nM con piel sana y 0,99nM y 17,08 con piel lesionada; valores menores de 1,92nM fueron detectados sólo en pulmón. El tratamiento con solución-PcAlCl retuvo el compuesto en EC y E+D de los animales con valores de 31,86 y 202,40nM con piel sana y 5,93 y 63,83nM con piel lesionada; se encontraron valores de 2,36nM y 20,33nM en los pulmones y valores entre 1,58 y 5,80nM en otros órganos. La piel lesionada presentó regeneración del epitelio, desprendimiento de queratina, infiltrado celular y neovascularización. La PcAlCl retenida en EC y E+D indicó la eficacia de las formulaciones para penetrar el EC y retener el compuesto en las capas viables de la piel. El tratamiento con nano-PcAlCl permeó el EC, se retuvo en E+D y no presentó distribución hacia órganos.

A successful formulation contained aluminum phthalocyanine chloride (ClAlPc) able for cutaneous leishmaniasis (CL) ensures the skin permeation and retention of the compound in dermis, a place where macrophages infected with Leishmania are located. The aim of this study was to determine the ClAlPcex vivo permeation and retention in Wistar rat skin and its distribution in animals with healthy skin and surgically damaged skin. Two formulations were prepared: nanoemulsion (ClAlPc-nano) and solution (ClAlPc-solution). The diffusion was determined using Franz diffusion cells with Wistar rat skin as membrane after 12 and 24 hours of testing. Retention in stratum corneum (SC) and epidermis plus dermis (E+D) was determined by the tape stripping method and organic solvent extraction. The distribution was performed after the topical application of formulations analyzing the CLAlPc concentration in the skin layers and organs by fluorometry. The results were expressed as nM/mg of tissue of ClAlPc. Simultaneously, skin biopsies were taken in order to determine their histological characteristics. ClAlPc formulations were effective in maintaining compound solubility and spectroscopic characteristics. ClAlPc was unable to pass completely through the skin; its skin retention was related with the used formulation, time of assays and type of skin layer. After 12 and 24 hours, the SC retention induced by ClAlPc-nano treatment was 99.73 and 79.40nM and by ClAlPc-solution was 66.73 and 57.01nM. In E+D the retention induced by ClAlPc-nano was 40.94 and 62.49nM and by ClAlPc-solution was 81.92 and 50.28nM. In SC, ClAlPc-nano showed greater retention after 12 and 24 hours, while in E+D, ClAlPc-solution was greater retained at 12 hours and ClAlPc-nano at 24 hours. After the permeation assays, detachment and reduction in epithelial layers were observed in skin membranes. In Wistar rats, ClAlPc-nano placed on healthy skin retained the compound in E+D and SC with values of 33.18nM and 6.43nM and placed on damaged skin retained in E+D in SC with values of 17.08nM and 0.99nM respectively; no organs distribution occur, except in lung where values of 0.82nM in animals with healthy skin and 1.92nM in animals with damaged skin were observed. ClAlPc-solution induced retention of 31.86 in SC and 202,40nM in E+D placed on healthy skin and 5.93 in SC and 63.83nM E+D placed on damaged skin; concentrations in lung with values of 2,36nM after application in animals with healthy skin and 20,33nM in animals with damaged skin were observed. In addition, ClAlPc-solution promoted, after application on damaged skin, distribution of ClAlPc to other organs with values between 1.58 and 5.80nM. In animals without skin injury, normal histologic skin anatomy were observed after treatment. In contrast, epithelial regeneration, detachment of keratin, loss of cellular differentiation, cellular infiltration and neovascularization were observed in animals with skin injury. The efficacy of the formulation to penetrate the SC and be retained in the viable skin layers was demonstrated. The in vivo ClAlPc-biodistribution was related on its concentration and skin state. A nanoemulsion contained ClAlPc, represents a good system of drug delivery because induce both the SC penetration and E+D retention, without systemic organ distribution even when presented tissue repair and regeneration. A ClAlPc-nano prepared in this work constitutes a good formulation for the topical application of ClAlPc in LC treatment.

A study of single-walled carbon nanotubes modified by organics of the phthalocyanine category / 西安交通大学学报·英文版

Organics of the phthalocyanine category have very good nonlinear optical properties. The single-walled carbon nanotubes were modified by using the phenoxy phthalocyanine. Characterization analysis was made by means of the transmission electron microscope (TEM), ultraviolet visible absorptive spectra, fluorescent spectra and Raman spectra. Under the TEM, it was observed that the composite looked like sugarcoated haws. By comparing the ultraviolet visible absorptive spectra before and after absorption, it was disclosed that the spectral intensity and the intensity of the peaks in the fluorescent spectra dropped remarkably. This shows that the single-walled carbon nanotubes have absorbed a large number of phenoxy phthalocyanines. Raman analysis revealed that in the Raman spectra, the position of the main peaks of the single-walled carbon nanotubes after absorption moved in the direction of long waves. The analysis suggests that the movement of the Raman spectra results from the change in the state of the single-walled carbon nanotubes before and after absorption.

A study of single-walled carbon nanotubes modified by organics of the phthalocyanine category / 药物分析学报

Organics of the phthalocyanine category have very good nonlinear optical properties. The single-walled carbon nanotubes were modified by using the phenoxy phthalocyanine. Characterization analysis was made by means of the transmission electron microscope (TEM), ultraviolet visible absorptive spectra, fluorescent spectra and Raman spectra. Under the TEM, it was observed that the composite looked like sugarcoated haws. By comparing the ultraviolet visible absorptive spectra before and after absorption, it was disclosed that the spectral intensity and the intensity of the peaks in the fluorescent spectra dropped remarkably. This shows that the single-walled carbon nanotubes have absorbed a large number of phenoxy phthalocyanines. Raman analysis revealed that in the Raman spectra, the position of the main peaks of the single-walled carbon nanotubes after absorption moved in the direction of long waves. The analysis suggests that the movement of the Raman spectra results from the change in the state of the single-walled carbon nanotubes before and after absorption.