Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment

Abstract We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studies.

Description of the complexity of prescribed medication regimens in primary health care of Ribeirão Preto - SP

Introduction: Pharmacotherapy is the main therapeutic resource for the management of diseases. However, the number of drugs prescribed, dose frequency, and mode of administration can make the treatment more complex and influence treatment outcomes. The aim of this study was to measure the complexity of prescribed medication regimens in primary health care (PHC) services in Ribeirão Preto, Brazil. Methods: This cross-sectional study included 1,009 participants: 889 from primary health units and 120 from family health units in Ribeirão Preto, Brazil. Treatment complexity was assessed using the Medication Regimen Complexity Index (MRCI). Results: MRCI mean scores were 12.5 points (SD = 9.3) and dose frequency was the major contributor to increase the score. The complexity of pharmacotherapy showed a significant correlation with the number of prescribed medications (r = 0.93, p < 0.01), but not with patients' age (r = 0.28, p < 0.01). There is also no difference in complexity between the sexes (p = 0.83) and the types of primary health care service (p = 0.31). An analysis of variance revealed that patients with lower levels of education receive more complex prescriptions (p < 0.01). Conclusions: The pharmacotherapy prescribed in PHC services from Ribeirão Preto, Brazil is complex, and there is a need to concentrate efforts and adopt strategies to simplify drug prescription without compromising patient's clinical status.

Adequação da prescrição de medicamentos na Atenção Primária à Saúde de Ribeirão Preto-SP: estudo transversal / Adequacy of drug prescriptions in the Primary Health Care of Ribeirão Preto-SP: a cross-sectional study / Adecuación de las prescripciones de medicamentos en la Atención Primaria de Salud de Ribeirão Preto-SP: estudio transversal

Objetivo: Este estudo transversal visa analisar comparativamente as prescrições de medicamentos provenientes da atenção básica tradicional (Unidades Básicas de Saúde - UBS) com as da Estratégia de Saúde da Família (ESF). Métodos: Foram incluídas 1053 prescrições, alocadas em dois grupos: 932 provenientes de UBS e 121 da ESF. Tais prescrições foram analisadas de acordo com a adequação aos itens legalmente exigidos e aos indicadores de qualidade (presença de antimicrobianos, presença de injetáveis, uso da denominação oficial, uso da relação de medicamentos essenciais, média de medicamentos prescritos). Resultados: As prescrições da ESF se mostraram estatisticamente mais completas quanto à presença do endereço do prescritor (82,6% UBS, 96,7% ESF), à ausência de rasuras (90,3% UBS, 96,7% ESF) e ao cumprimento dos aspectos legais exigidos referentes ao uso do medicamento, sendo eles: forma farmacêutica (70,7% UBS, 80,2% ESF), dose (70,9% UBS, 79,3% ESF), posologia (63,0% UBS, 75,2% ESF), via de administração (58,3% UBS, 83,5% ESF) e duração do tratamento (76,9% UBS, 92,6% ESF). Os resultados dos indicadores de qualidade da prescrição se aproximaram nos dois modelos de atenção básica e estão de acordo com os valores recomendados, com exceção da média de medicamentos prescritos, a qual evidenciou uma tendência à polifarmácia no município (3,9 medicamentos por prescrição na UBS e 3,5 na ESF). Conclusão: Apesar dos resultados revelarem práticas inapropriadas na prescrição de medicamentos na Atenção Primária como um todo, há evidências de que as prescrições da ESF estão mais próximas ao padrão ideal, o que pode favorecer o Uso Racional de Medicamentos.

Objective: This cross-sectional study aims to comparatively analyze drug prescriptions from the traditional basic health care service (Basic Health Units - BHU) with those from Family Health Strategy (FHS). Methods: A total of 1053 prescriptions were included, allocated in two groups: 932 from BHU and 121 from FHS. These prescriptions were analyzed according with compliance to legally required items and quality indicators (presence of antimicrobials, presence of injectable, use of the official name, use of the list of essential drugs, average of drugs prescribed). Results: The ESF prescriptions were more complete regarding the presence of the prescriber's address (82.6% BHU, 96.7% FHS), the absence of erasures and overwritten words (90.3% BHU, 96.7% FHS) and with compliance to legally required items related to use of drugs, being: pharmaceutical form (70.7% BHU, 80.2% FHS), dose (70.9% BHU, 79.3% FHS), posology (63.0% BHU, 75.2% FHS), administration route (58.3% BHU, 83.5% FHS) and time of therapy (76.9% BHU, 92.6% FHS). The results of the indicators of quality of prescription are approximated in both models of basic attention and according to the recommended values, with the exception of the average of drugs prescribed, which showed a tendency to polypharmacy at county (3.9 drugs per prescription at the BHU and 3.5 at the FHS). Conclusion: although the results reveal inappropriate practices in drug prescription at Primary Health Care services as a whole, there are evidence that prescriptions from FHS are closer to the ideal pattern, which may favor the Rational Use of Drugs.

Objetivo: Este estudio transversal tuvo como objetivo comparar prescripciones médicas de la atención primaria tradicional (Unidades Básicas de Salud - UBS) con las de la Estrategia de Salud Familiar (ESF). Métodos: Se incluyeron 1053 prescripciones, divididas en dos grupos: 932 de la UBS y 121 de la ESF. Estas prescripciones se analizaron de acuerdo con la adecuación de los ítems legalmente requeridos y a los indicadores de calidad (presencia de antimicrobianos, presencia de inyectables, uso de la denominación oficial, uso de la relación de medicamentos esenciales, número medio de los medicamentos prescritos). Resultados: Las prescripciones de la ESF eran estadísticamente más completas debido a la presencia de la dirección del prescriptor (82,6% UBS, 96,7% ESF), en la ausencia de tachaduras (90,3% UBS, 96,7% ESF) y en el cumplimiento de los aspectos legales requeridos referentes al uso del medicamento, siendo ellos: forma farmacéutica (70,7% UBS, 80,2% ESF), dosis (70,9% UBS, 79,3% ESF), posología (63,0% UBS, 75,2% ESF), vía de administración (58,3% UBS, 83,5% ESF) y duración del tratamiento (76,9% UBS, 92,6% ESF). Los resultados de los indicadores de calidad de la prescripción fueron similares en los dos modelos de atención primaria y están de acuerdo con los valores recomendados, excepto el número medio de los medicamentos prescriptos, que mostró una tendencia a la polifarmacia en el municipio (3,9 medicamentos por prescripción en la UBS y 3,5 en la ESF). Conclusión: Aunque los resultados indican prácticas inadecuadas en la prescripción de medicamentos en atención primaria en general, existen evidencias de que las prescripciones de la ESF son más cercanas a los estándares, lo que puede favorecer el Uso Racional de Medicamentos.

Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Ursolic acid is a promising candidate for treatment of Chagas disease; however it has low aqueous solubility and intestinal absorption, which are both limiting factors for bioavailability. Among the strategies to enhance the solubility and dissolution of lipophilic drugs, solid dispersions are growing in popularity. In this study, we employed a mixture of the surfactants poloxamer 407 with sodium caprate to produce a solid dispersion containing ursolic acid aimed at enhancing both drug dissolution and in vivo trypanocidal activity. Compared to the physical mixture, the solid dispersion presented higher bulk density and smaller particle size. Fourier Transform Infrared Spectroscopy results showed hydrogen bonding intermolecular interactions between drug and poloxamer 407. X-ray diffractometry experiments revealed the conversion of the drug from its crystalline form to a more soluble amorphous structure. Consequently, the solubility of ursolic acid in the solid dispersion was increased and the drug dissolved in a fast and complete manner. Taken together with the oral absorption-enhancing property of sodium caprate, these results explained the increase of the in vivo trypanocidal activity of ursolic acid in solid dispersion, which also proved to be safe by cytotoxicity evaluation using the LLC-MK2 cell line.

O ácido ursólico é um candidato promissor para o tratamento da doença de Chagas, contudo este fármaco possui baixa solubilidade aquosa e limitada absorção intestinal, ambos os fatores limitantes da biodisponibilidade. Entre as estratégias para potencializar a solubilidade e a dissolução de fármacos lipofílicos, as dispersões sólidas estão crescendo em popularidade. Neste estudo, empregamos mistura dos tensoativos, poloxamer 407 e caprato de sódio, para produzir dispersão sólida contendo ácido ursólico, com o objetivo de aumentar tanto a dissolução do fármaco quanto a atividade tripanocida in vivo. Comparada à mistura física, a dispersão sólida apresentou maior densidade e menor tamanho de partícula. Os resultados da análise de espectroscopia no infravermelho com transformada de Fourier mostraram interações intermoleculares do tipo ligações de hidrogênio entre o fármaco e o poloxamer 407. Os experimentos de difratometria de raio-X revelaram a conversão do fármaco de sua forma cristalina para a forma amorfa, mais solúvel. Consequentemente, a solubilidade do ácido ursólico em dispersão sólida foi aumentada e o fármaco dissolveu-se de maneira mais rápida e completa. Em conjunto com as propriedades promotoras de absorção oral do caprato de sódio, estes resultados explicaram o aumento da atividade tripanocida in vivo do ácido ursólico em dispersão sólida, que também se provou segura após avaliação de citotoxicidade empregando a linhagem celular LLC-MK2.

A study of the characteristics and in vitro permeation properties of CMC/ chitosan microparticles as a skin delivery system for vitamin E

Carboxymethylcellulose (CMC)/chitosan microparticles containing vitamin E were prepared by a complex coacervation method and their potential use as a topical delivery system was evaluated. Morphology, particle size distribution, encapsulation yield, physical and chemical stability, in vitro release and permeation through skin were studied. The microparticles appeared to be spherical, with a homogeneous surface and were not aggregated. Mean diameters ranged from 2.7 to 7.6 µm and the encapsulation yield was 81 percent. Chemical stability studies indicated a protection of encapsulated vitamin E, of 8.1 percent for O/W and of 10.83 percent for W/O emulsions, following storage at 45 °C for 60 days. Forty-eight percent of vitamin E, determined by HPLC, were released within 24 hours. In vitro permeation and retention studies showed a higher penetration rate of vitamin E in the free and encapsulated forms, from the W/O emulsion. The carriers studied seem to be promising systems for topical administration.

HPLC assay of lidocaine in vitro dissolution test of the Poloxamer 407 gels

Apresenta-se método simples de cromatografia líquida de alta eficiência (CLAE) para análise da lidocaína em meio aquoso, após estudo de liberaçäo in vitro. A lidocaina foi analisada usando-se coluna LichroCART RP-18 (5mm, 125x4mm), fase móvel constituída de acetonitrila: tampäo fosfato de sódio 0,05 M, pH 6 (35:65), adicionada de 0,05 por cento de dietilamina com fluxo de 1 mL/min. O tempo de retençäo foi de 7,9min. A linearidade do método foi de 1,25 a 25 µg/mL com coeficiente de variaçäo intra-ensaio e inter-ensaio menor que 3,5 por cento.

Potential incorporation of 5-aminolevulinic acid in micelles and stratum corneum lipids liposomes: fluorescence quenching studies

The quenchings of pyrene fluorescence by 5-aminolevulinic acid (5-ALA) in dodecyl sulfate (SDS) micelles and stratum corneum lipids liposomes (SCLLs) were studied in order to verify the capacity of incorporation of 5-ALA in these systems. Static and dynamic quenching constants based on the simultaneous determination of fluorescence intensity quenching and fluorescence decay measurements were determined. 5-ALA was incorporated at crescent concentrations in SDS micelles and SCLLs containing the fluorescent probe (pyrene, 1,15 x '10 POT.menos 5 M') and the rate constants of quenching (kq) of pyrene were determined. 5-ALA was able to quench the fluorescence of the probe in both systems studied. A greater extent...