Preparation of berberine-naringin dual drug-loaded composite microspheres and evaluation of their antibacterial-osteogenic properties / 中国修复重建外科杂志

OBJECTIVE@#To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects.@*METHODS@#The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively.@*RESULTS@#NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05).@*CONCLUSION@#NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.

Desarrollo de un nanosistema para la liberación de fármacos intravítreo / Development of intravitreal nanosistema for drugs release

La inyección intravítrea ha sido la vía de administración más eficaz para el tratamiento de enfermedades vitreorretinianas. Su práctica continua, no es agradable para los pacientes y a su vez podría causar complicaciones indeseadas. El presente trabajo tuvo como objetivo desarrollar un nanosistema de liberación polímero-terapéutico (conjugado)/nanopartícula, utilizando Dextrano y Quitosano como polímeros transportadores biodegradables, hidrosolubles y compatibles a nivel ocular así como Hemisuccinato de Metilprednisolona como fármaco modelo. Primeramente, el fármaco fue capaz de unirse covalentemente a dos Dextranos de pesos moleculares 10 y 70 kDa. En función del contenido del componente activo y perfil de liberación, se seleccionó el Hemisuccinato de Metilprednisolona-Dextrano 10 kDa para elaborar las nanopartículas de Quitosano por el método de gelificación iónica empleando tripolifosfato sódico como agente entrecruzante. Por último, las nanopartículas fueron cubiertas con lactosa aplicando el secado por atomización. Se evaluó morfología, distribución de tamaño de las partículas, carga superficial, contenido y eficacia de captura del fármaco. Las partículas esféricas presentaron superficies lisas y uniformes. El pH tuvo influencia en el tamaño de las partículas observándose una distribución bimodal a pHs ≈ pKa del Quitosano y unimodal con un rango entre 130 - 170 nm a pHs < pKa. La variación de los potenciales Zeta entre los compuestos involucrados en la reacción, indicaron la posible ocurrencia de la misma. Al comparar la liberación del conjugado con las Nanopartículas a pH fisiológico, se observó que la encapsulación retrasó la liberación del fármaco alrededor de un 50%. Las nanopartículas recubiertas formaron micropartículas de 1.780 ± 0,5 nm, lo que favoreció su dispersibilidad en agua. Este nuevo nanosistema, evidenció su posible potencial en el desarrollo de formulaciones de liberación intravítrea, que reduzca la frecuencia de administración, ofreciendo una excelente alternativa que proporcione un mayor grado de satisfacción y mejore la calidad de vida del paciente.

Mechanical properties and total hydroxycinnamic derivative release of starch/glycerol/Melissa officinalis extract films / Propriedades mecânicas e a liberação total hidroxicinâmicos derivados e extração de película de amido / glicerol / Melissa officinalis

The aim of this study was to investigate the mechanical properties of starch/glycerol/Melissa officinalis, a topical drug delivery system for labial herpes treatment. Four films were prepared with different concentrations of starch, glycerol, and Melissa officinalis extract. The results revealed that increasing the glycerol concentration in the film reduced elasticity modulus and tensile strength, exhibiting a plasticizing effect. The increase in free volume resulted in increased release of hydroxycinnamic derivatives expressed as rosmarinic acid.

O objetivo deste trabalho foi estudar as propriedades mecânicas e o mecanismo de liberação de um sistema tópico de liberação prolongada para o tratamento do Herpes labial a partir de filmes de amido/glicerol/extrato de Melissa officinalis, planta com comprovada atividade antiviral. Foram obtidos quatro filmes poliméricos com diferentes concentrações de amido, glicerol e extrato de Melissa officinalis os quais foram caracterizados mecanicamente e determinado o perfil de liberação de derivados hidroxicinâmicos. Os resultados demonstraram que o aumento da concentração de glicerol no filme produz uma redução no módulo de elasticidade e na tensão de deformação como conseqüência do efeito plastificante. O aumento no volume livre do polímero resultou em aumento da liberação dos derivados hidroxicinâmicos expressos como ácido rosmarínico.

Avaliaçäo da perfomance clínica do uso prolongado do acetato de medroxiprogesterona (AMP) como anticoncepcional, no Ambulatório de Planejamento Familiar do Departamento de Tocoginecologia da UNICAMP / Clinical performance evaluation of extended use of medroxyprogesterone acetate as a contraceptive in the Ambulatório de Planejamento Familiar do Departamento de Tocoginecologia da UNICAMP

Foram estudados 1328 casos de usuários de acetato de medroxiprogesterona (AMP) como método anticoncepcional que iniciaram seu uso no período de janeiro de 1977 até dezembro de 1985. A performance clínica foi avaliada pelo método da tabela de vida. A taxa acumulada de gravidez foi de 0,2% no primeiro ano, 0,6% até o terceiro e 1,0% após cinco anos de uso. A vida média, tempo em que 50% das usuárias ainda contimuam usando o método, foi de 21 meses. As principais causas de descontinuaçäo, foram causas pessoais e näo relacionadas com o método, que representaram mais de 70% dos encerramentos. As causas médicas representaram menos de 25% do total de encerramento e entre elas a mais freqüente foi a alteraçäo menstrual. Os autores concluem que o AMP se mostrou um bom método no que diz respeito ao desempenho clínico e aceitaçäo

Effects of long-acting steroid contraceptives on ovarian and uterine histology of rats.

Subcutaneous injection of single doses (5 to 20 mg/kg) of DMPA or NE in virgin female rats caused reduction in number and diameter of CL, and increase in number of atretic and cystic follicles in the ovary. Histological examination of the endometrium of these animals showed low cubiodal cells with sparse distribution of low columnar cells, glands with atrophic changes and compact uterine stroma with or without patches of oedema. The results suggest regressive and atrophic changes in the ovary and endometrium.