Effect of Cilostazol-Loaded PCL/PEG Nanocapsules on Abdominal Aortic Tunics and Lipid Profile of Wistar Rats

Abstract Cilostazol (CLZ) is a phosphodiesterase III inhibitor with antiplatelet and vasodilator properties. It has been recently verified that CLZ plays a significant role in the arteries by inhibiting the proliferation and growth of muscle cells, increasing the release of nitric oxide by the endothelium and promoting angiogenesis. Considering these promising effects, the use of nanocapsules may be an interesting strategy to optimize its pharmacokinetics and pharmacodynamics at the vascular level for preventing atherosclerosis. The aim of this study was to evaluate the effect of cilostazol-loaded nanocapsules in the abdominal aortic tunics and on the lipid profile of Wistar rats in order to investigate its potential role in the prevention of atherosclerosis. Thirty-two animals were divided into four groups of eight animals, with 30-day treatment. Group 1 received nanoencapsulated CLZ; Group 2, control nanocapsules with no drug; Group 3, propylene glycol and water; and Group 4, a solution of CLZ in propylene glycol and water. After 30 days, there was no statistically significant difference between the groups regarding the cellularity and thickness of the arterial tunics of the abdominal aorta. However, the group that received nanoencapsulated CLZ (Group 1) had an improvement in HDL-c and triglyceride values compared to unloaded nanocapsules (Group 2).

Colombian propolis as starting material for the preparation of nanostructured lipid carriers

ABSTRACT The value of propolis is scientifically and commercially measured through the content of biologically active molecules as phenolic compounds and flavonoids; on the other hand, a high percentage of waxes in the propolis composition makes it a substandard beekeeping product. Colombian propolis is characterized by a high content of waxes; however, this drawback turns into an advantage when this material is used for preparing lipid nanocarriers. Accordingly, in this research work, a propolis-extracted material obtained by Randall method is characterized by differential scanning calorimetry, infrared spectroscopy, X-ray diffraction, and 1H-Nuclear Magnetic Resonance. Then, it is used for obtaining nanostructured lipid carriers by the emulsification-diffusion technique, whose recipe and operating work conditions were established by a Plackett-Burman statistical screening design. The obtained particles exhibit sizes less than 300 nm, polydispersity indices around 0.1, zeta potential values less than ±2 mV, good physical stability and they show to be safe in the in vitro irritation test. Thus, Colombian propolis arises as an attractive natural source for obtaining lipid carriers that could be used in pharmaceutical or cosmetic industries for developing innovative products.

Development of analytical method for quantification of antineoplastic in drug delivery systems

Nos últimos anos têm crescido cada vez mais o número de pesquisas envolvendo nanotecnologia para obtenção de medicamentos com liberação controlada, pois esses sistemas podem: proteger o fármaco de incompatibilidades tanto biológicas quanto físico-químicas assim como controlar a biodisponibilidade do fármaco. Embora com todas essas vantagens não existem métodos in vitro realmente capazes de prever com precisão a liberação dos fármacos por esses sistemas, por esse motivo, é muito importante o desenvolvimento de métodos de liberação in vitro para determinar a cinética de liberação desses sistemas.O presente trabalho teve como objetivo desenvolver e validar os métodos de eletroforese capilar (CE) e cromatografia líquida de alta eficiência (HPLC) para determinar a eficiência de encapsulação do fármaco imatinibe em nanopartículaspreviamente elaboradas e caracterizadas, assim como estudar sua liberação in vitro por CE. As nanopartículas foramdesenvolvidas pelo método de nanoprecipitaçãoe caracterizadas quanto ao tamanho, potencial zeta, morfologia e eficiência de encapsulação. A eletroforese capilar é uma técnica alternativa muito promissora em relação ao HPLC devido ao seu baixo custo, menor tempo de corrida e menos poluente ao meio ambiente. Os métodos de quantificação por CE e HPLCforam desenvolvidose validadossegundo as diretrizes do ICH, Farmacopeia Americana e ANVISA, permitindo desenvolver um estudo de liberação.As nanoesferas desenvolvidas apresentaram diâmetro médio próximo a 150nm, com índice de polidispersão menor que 0,1 e aproximadamente 90% de eficiência de encapsulação. Ambos métodos se mostraram lineares com coeficientes de determinação superiores a 0,99, os métodos se mostraram precisos (%DPR< 2), exatos(101,0±4,2% e 98,0±2,5% para HPLC e CE, respectivamente)e seletivos.O método de CE permitiu desenvolver um método de estudo de liberação independente das membranas de diálise

In recent years, there has been a growing number of researches involving nanotechnology to obtain controlled release drugs, these systems can: protect the drug against biological and physico-chemical incompatibilities; controlling the bioavailability of the drug. Although with all these advantages there are no in vitro methods really capable of accurately predicting drugs release by such systems, therefore, the development of in vitro release methods to determine the release kinetics of such systems is very important. The objective of the present work was to develop and validate capillary electrophoresis (CE) and HPLC methods to determine the encapsulation efficiency of the imatinib drug in previously elaborated and characterized nanoparticles, as well as to study its release in vitro by CE method. The nanoparticles were synthesized using the nanoprecipitation method and characterized by size, zeta potential, morphology and encapsulation efficiency. Capillary electrophoresis is a very promising alternative to HPLC because of its low cost, less runtime and less polluting environment. The CE and HPLC methodswere developed and validated according ICH, American Pharmacopoeia and ANVISA guidelines.Developed nanospheres had an average diameter close to 150nm, with polydispersity index less than 0.1 and approximately 90% encapsulation efficiency. Both methods were linear with determination coefficients higher than 0.99, the methods were precise (%RSD < 2), accurate (101.0±4,2% and 98.0±2,5% for HPLC and CE, respectively) and selective. Capillary electrophoresis method allowed to develop a drug release study independent of dialysis membranes

Effect on adhesion of a nanocapsules-loaded adhesive system

Abstract This study aimed to evaluate the in situ degree of conversion, contact angle, and immediate and long-term bond strengths of a commercial primer and an experimental adhesive containing indomethacin- and triclosan-loaded nanocapsules (NCs). The indomethacin- and triclosan-loaded NCs, which promote anti-inflammatory and antibacterial effects through controlled release, were incorporated into the primer at a concentration of 2% and in the adhesive at concentrations of 1, 2, 5, and 10%. The in situ degree of conversion (DC, n=3) was evaluated by micro-Raman spectroscopy. The contact angle of the primer and adhesive on the dentin surface (n = 3) was determined by an optical tensiometer. For the microtensile bond strength µTBS test (12 teeth per group), stick-shaped specimens were tested under tensile stress immediately after preparation and after storage in water for 1 year. The data were analyzed using two-way ANOVA, three-way ANOVA and Tukey's post hoc tests with α=0.05. The use of the NC-loaded adhesive resulted in a higher in situ degree of conversion. The DC values varied from 75.07 ± 8.83% to 96.18 ± 0.87%. The use of NCs in only the adhesive up to a concentration of 5% had no influence on the bond strength. The contact angle of the primer remained the same with and without NCs. The use of both the primer and adhesive with NCs (for all concentrations) resulted in a higher contact angle of the adhesive. The longitudinal μTBS was inversely proportional to the concentration of NCs in the adhesive system, exhibiting decreasing values for the groups with primer containing NCs and adhesives with increasing concentrations of NCs. Adhesives containing up to 5% of nanocapsules and primer with no NCs maintained the in situ degree of conversion, contact angle, and immediate and long-term bond strengths. Therefore, the NC-loaded adhesive can be an alternative method for combining the bond performance and therapeutic effects. The use of an adhesive with up to 5% nanocapsules containing indomethacin and triclosan and a primer with no nanocapsules maintained the long-term bond performance.

Sistemas biodegradáveis contendo acetato de prednisolona para administração orbitária / Biodegradable systems containing prednisolone acetate for orbital administration

OBJETIVO: O presente estudo objetivou o desenvolvimento e a avaliação de um sistema biodegradável de liberação de fármacos com característica de liberação prolongada, destinado à administração orbitária de acetato de prednisolona (AP). MÉTODOS: O sistema desenvolvido, na forma de microesferas (MEs) de poli-e-caprolactona (PCL) contendo o AP, foi obtido pelo método de evaporação de solvente. As MEs foram caracterizadas por microscopia eletrônica de varredura (MEV), calorimetria diferencial exploratória (DSC), avaliação do teor de encapsulação e pelo perfil de liberação in vitro. O perfil de liberação in vivo foi avaliado em coelhos após administração peribulbar de uma suspensão aquosa das MEs. A biocompatibilidade local do sistema foi verificada por meio de análise histopatológica da região de implantação. RESULTADOS: Após obtenção das MEs, a análise morfológica por MEV mostrou a viabilidade do método de obtenção do sistema. O teor de AP encapsulado foi de 43 ± 7 por cento e pode ser considerado bastante satisfatório. A caracterização do sistema por DSC, além de confirmar a sua estabilidade, não indicou a existência de interação entre o fármaco e o polímero. O estudo de liberação in vitro indicou que o sistema apresenta perfil de liberação prolongada. O estudo in vivo confirmou o perfil de liberação prolongado do AP a partir das MEs, sugerindo, também, a viabilidade do sistema devido à ausência de toxicidade local. CONCLUSÃO: O conjunto dos resultados obtidos neste trabalho é relevante e credencia o sistema desenvolvido como uma possível alternativa ao tratamento de orbitopatias inflamatórias.

PURPOSE: The present study aimed to evaluate an injectable extended-release formulation of prednisolone acetate (PA) for orbital administration. METHODS: Microspheres (MEs) of poly-e-caprolactone (PCL) containing PA were developed by the method of solvent evaporation. The MEs obtained were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), encapsulation efficiency and in vitro release profile. The in vivo release profile was evaluated in rabbits after periocular injection of an aqueous suspension of MEs. The local biocompatibility of the system was verified by histopathologic analysis of the deployment region. RESULTS: After MEs preparation, morphological analysis by SEM showed the feasibility of the employed method. The content of PA encapsulated was 43 ± 7 percent and can be considered as satisfactory. The system characterization by DSC technique, in addition to confirm the system stability, did not indicate the existence of interaction between the drug and the polymer. The in vitro release study showed the prolonged-release features of the developed system. Preliminary in vivo study showed the absence of local toxicity and confirmed the prolonged release profile of PA from MEs, suggesting the viability of the developed system for the treatment of orbital inflammatory diseases. CONCLUSION: The results obtained in this work are relevant and accredit the system developed as a possible alternative to the treatment of inflammatory orbitopathy.