Thermal behavior and stability of biodegradable spray-dried microparticles containing triamcinolone

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Thermal analysis of biodegradable microparticles containing ciprofloxacin hydrochloride obtained by spray drying technique

Thermal analysis has been extensively used to obtain information about drug-polymer interactions and to perform pre-formulation studies of pharmaceutical dosage forms. In this work, biodegradable microparticles of poly(D,L-lactide-co-glycolide) (PLGA) containing ciprofloxacin hydrochloride (CP) in various drug:polymer ratios were obtained by spray drying. The main purpose of this study was to investigate the effect of the spray drying process on the drug-polymer interactions and on the stability of microparticles using differential scanning calorimetry (DSC), thermogravimetry (TG) and derivative thermogravimetry (DTG) and infrared spectroscopy (IR). The results showed that the high levels of encapsulation efficiency were dependant on drug:polymer ratio. DSC and TG/DTG analyses showed that for physical mixtures of the microparticles components the thermal profiles were different from those signals obtained with the pure substances. Thermal analysis data disclosed that physical interaction between CP and PLGA in high temperatures had occurred. The DSC and TG profiles for drug-loaded microparticles were very similar to the physical mixtures of components and it was possible to characterize the thermal properties of microparticles according to drug content. These data indicated that the spray dryer technique does not affect the physicochemical properties of the microparticles. In addition, the results are in agreement with IR data analysis demonstrating that no significant chemical interaction occurs between CP and PLGA in both physical mixtures and microparticles. In conclusion, we have found that the spray drying procedure used in this work can be a secure methodology to produce CP-loaded microparticles. (C) 2007 Elsevier B.V. All rights reserved.

Validation of an HPLC Method for quantitative Determination of Benzocaine in PHBV-Microparticles and PLA-Nanoparticles

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Preparation and antimicrobial activity of gelatin microparticles containing propolis against oral pathogens

Gelatin microparticles containing propolis ethanolic extractive solution were prepared by spray-drying technique. Particle,, with regular morphology, mean diameter ranging of 2.27 mu m to 2.48 mu m, and good entrapment efficiency for propolis were obtained. The in vitro antimicrobial activity of microparticles was evaluated against microorganisms of oral importance (Enterococcus faecalis, Streptococcus salivarius, Streptococcus sanguinis, Streptococcus mitis, Streptococcus mutans, Streptococcus sobrinus, Candida albicans, and Lactobacillus casei). The utilized techniques were diffusion in agar and determination of minimum inhibitory concentration. The choice of the method to evaluate the antimicrobial activity of microparticles showed be very important. The microparticles displayed activity against all tested strains of similar way to the propolis, showing greater activity against the strains of E. salivarius, S. sanguinis, S. mitis, and C albicans.

Phagocytosis of PLGA microparticles in rat peritoneal exudate cells: A time-dependent study

With the purpose of enhancing the efficacy of microparticle-encapsulated therapeutic agents, in this study we evaluated the phagocytic ability of rat peritoneal exudate cells and the preferential location of poly(D,L-lactide-co-glycolic acid) (PLGA) microparticles inside these cells. The microparticles used were produced by a solvent evaporation method and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Size distribution analysis using DLS and SEM showed that the particles were spherical, with diameters falling between 0.5 and 1.5 mu m. Results from cell adhesion by SEM assay, indicated that the PLGA microparticles are not toxic to cells and do not cause any distinct damage to them as confirmed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Among the large variety of cell populations found in the peritoneal exudates (neutrophils, eosinophils, monocytes, and macrophages), TEM showed that only the latter phagocytosed PLGA microparticles, in a time-dependent manner. The results obtained indicate that the microparticles studied show merits as possible carriers of drugs for intracellular delivery.

Characterization of PLGA microparticles as a drug carrier for 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one. Ultrastructural study of cellular uptake and intracellular distribution

Here we describe the application of microparticles (MPs) for the delivery and release of the drug a benzopsoralen. We also evaluated the intracellular distribution and cellular uptake of the drug by using an encapsulation technique for therapeutic optimization. MPs containing the compound 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one (psoralen A) were prepared by the solvent evaporation technique, and parameters such as particle size, drug encapsulation efficiency, effect of the encapsulation process on the drug's photochemistry, zeta potential, external morphology, and < i > in vitro release behavior were evaluated. The intracellular distribution of MPs as well as their uptake by tissues were monitored. Size distribution studies using dynamic ligh scattering and scanning electron microscopy revealed that the MPs are spherical in shape with a diameter of 1.4 mu m. They present low tendency toward aggregation, as confirmed by their zeta potential (+10.6 mV). The loading efficiency obtained was 75%. As a consequence of the extremely low diffusivity of the drug in aqueous medium, the drug release profile of the MPs in saline phosphate buffer (pH 7.4) was much slower than that obtained in the biological environment. Among the population of peritoneal phagocytic cells, only macrophages were able to phagocytose poly-d,l-lactic-co-glycolic acid (PLGA) MP. The use of psoralen A in association with ultraviolet light (360 nm) revealed morphological characteristics of cell damage such as cytoplasmic vesiculation, mitochondria condensation, and swelling of both the granular endoplasmatic reticulum and the nuclear membrane. These results indicate that PLGA MP could be a promising delivery system for psoralen in connection with ultraviolet irradiation therapy (PUVA).

In vitro release of propolis from gelatin microparticles prepared by spray-drying technique

The purpose of this study was to investigate the in vitro release of propolis from gelatin microparticles. Gelatin microparticles containing propolis extractive solution (PES) were prepared by spray-drying technique. Microparticles with a mean diameter of 2.50 μm and with regular morphology were obtained. The entrapment efficiency of propolis in the microparticles was over 39%. Spray-drying showed to be a feasible method for the preparation of gelatin microparticles containing propolis. Comparing to PES, the in vitro release of propolis from gelatin microparticles in aqueous medium was slower, considering markers 1 and 2. Thus, it was possible to transform a liquid propolis dosage form into a solid one, improving manipulation, packaging and storage and with modified release in aqueous medium, comparatively to the ethanolic extract of the drug.

Studies on the formation of complex coacervates between chitosan and alginate during microparticles preparation

The formation of complex coacervates between chitosan and alginate was evaluated during microparticles formation. Mass ratio between polyelectrolytes and calcium chloride concentration were determinated by conductimetric analysis and by calcium ions quantification, respectively. Inert microparticles were prepared using a complex coacervation method in W/O emulsion and morphological analyses of microparticles were carried out. This method enabled the production of spherical particles, with slightly rough surface and narrow size distribution with maximal diameter of 10 μm.

Development and validation of HPLC method for quantitative analysis of triamcinolone in biodegradable microparticles

A simple, rapid, selective and specific high performance liquid chromatographic (HPLC) method for quantitative analysis of the triamcinolone in polylactide-co-glycolide acid (PLGA) microparticles was developed. The chromatographic parameters were reversed-phase C18 column, 250mm x 4.6mm, with particle size 5 μm. The column oven was thermostated at 35°C ± 2°C. The mobile phase was methanol/water 45:55 (v/v) and elution was isocratic at a flow-rate of 1 mL.mL-1. The determinations were performed using a UV-Vis detector at 239 nm. The injected sample volume was 10 μL. The standard curve was linear (r2 > 0.999) in the concentration range 100-2500 ng.mL-1. The method showed adequate precision, with a relative standard deviation (RSD) was smaller than 3%. The accuracy was analyzed by adding a standard drug and good recovery values were obtained for all drug concentrations used. The method showed specificity and selectivity with linearity in the working range and good precision and accuracy, making it very suitable for quantitation of triamcinolone in PLGA microparticles.

Development of a new method to prepare nano-/microparticles loaded with extracts of azadirachta indica, their characterization and use in controlling plutella xylostella

Biodegradable nanoparticles have been widely explored as carriers for controlled delivery of therapeutic molecules; however, studies describing the development of nanoparticles as carriers for biopesticide products are few. In this work, a new method to prepare nanoparticles loaded with neem (Azadirachta indica) extracts is presented. In this study, nanoparticles were formulated as colloidal suspension and (spray-dried) powder and characterized by evaluating pH, particle size, zeta potential, morphology, absolute recovery, and entrapment efficiency. A high-performance liquid chromatography method was used for nanoparticle characterization. The best formulations presented absolute recovery and entrapment efficiencies of approximately 100% and a release profile based on swelling and relaxation of the polymer or polymer erosion. The biological data of the formulated products against Plutella xylostella showed 100% larval mortality. The nanoparticle information improved the stability of neem products against ultraviolet radiation and increased their dispersion in the aqueous phase. © 2013 American Chemical Society.

Structural and thermal properties of spray-dried methotrexate-loaded biodegradable microparticles

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Producing xylan/Eudragit (R) S100-based microparticles by chemical and physico-mechanical approaches as carriers for 5-aminosalicylic acid

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

High protein microparticles produced by ionic gelation containing Lactobacillus acidophilus for feeding pacu larvae

Microparticles with high protein content can be used as diets to mimic the proximate composition of Artemia nauplii. After production, the particles were characterized with respect to their proximate composition, mean size, morphology, and rehydration behavior after drying. The protein content, lipid content and the particle moisture were similar to Artemia nauplii, with mean values of 50, 23, and 85%, respectively. Additionally, the particles were used in a pacu (Piaractus mesopotamicus) larval growth experiment. Also, the probiotic Lactobacillus acidophilus was added to one of the diets, and the effects of the diets were evaluated on larvae growth and stress resistance. Larvae fed the experimental diets had lower growth than larvae fed with Artemia nauplii or a commercial diet. All of the evaluated diets, including the experimental ones, showed high ingestion rates (>90%). In the stress test by air exposure, larvae fed with the microparticle without probiotic exhibited a significantly higher mortality than those fed the commercial diet or those fed with Artemia nauplii. The low growth rates may have been due to a potential nutritional inadequacy with respect to the low mineral/vitamin content of the experimental diets. (C) 2014 Elsevier Ltd. All rights reserved.

Mechanical strain induces the production of spheroid mineralized microparticles in the aortic valve through a RhoA/ROCK-dependent mechanism

Calcific aortic valve disease (CAVD) is a chronic disorder characterized by an abnormal mineralization of the leaflets, which is accelerated in bicuspid aortic valve (BAV). It is suspected that mechanical strain may promote/enhance mineralization of the aortic valve. However, the effect of mechanical strain and the involved pathways during mineralization of the aortic valve remains largely unknown. Valve interstitial cells (VICs) were isolated and studied under strain conditions. Human bicuspid aortic valves were examined as a model relevant to increase mechanical strain. Cyclic strain increased mineralization of VICs by several-fold. Scanning electron microscope (SEM) and energy dispersive X-ray (EDX) analyses revealed that mechanical strain promoted the formation of mineralized spheroid microparticles, which coalesced into larger structure at the surface of apoptotic VICs. Apoptosis and mineralization were closely associated with expression of ENPP1. Inhibition of ENPP1 greatly reduced mineralization of VIC cultures. Through several lines of evidence we showed that mechanical strain promoted the export of ENPP1-containing vesicles to the plasma membrane through a RhoA/ROCK pathway. Studies conducted in human BAV revealed the presence of spheroid mineralized structures along with the expression of ENPP1 in areas of high mechanical strain. Mechanical strain promotes the production and accumulation of spheroid mineralized microparticles by VICs, which may represent one important underlying mechanism involved in aortic valve mineralization. RhoA/ROCK-mediated export of ENPP1 to the plasma membrane promotes strain-induced mineralization of VICs.

Physicochemical aspects involved in methotrexate release kinetics from biodegradable spray-dried chitosan microparticles

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)