Preparation, characterization and antiproliferative activity of thymoquinone-beta-cyclodextrin self assembling nanoparticles.

Thymoquinone (TQ) was complexed with beta-cyclodextrin (CD) to form nanosized aggregates. Various TQ:CD ratios were tested and it was found that the ratio of (1:0.25) TQ:CD formed distinguishable nanoparticles with minimum toxicity towards normal cells. These nanoparticles had an average size of 445 +/- 100 nm with a charge 21.8 mV using Zeta-sizer. Particle size measurement using scanning electron microscopy (SEM) showed an average size of 400 nm and it also revealed the presence of smaller structures, with an average size of 50 nm. The in vitro antiproliferative activity on MCF7 cells was determined using MTT assay and an IC50 of 4.70 +/- 0.60 microM for TQ-CD nanoparticles in comparison to 24.09 +/- 2.35 microM of free TQ solution after 72 h of incubation. Simultaneously, TQ-CD nanoparticles showed lesser toxicity than TQ solution using human periodontal fibroblasts as a model for normal cells. It could be concluded from the results that TQ loaded cyclodextrin nanoparticles might serve as a potential nanocarrier to improve TQ solubility as well as its antiproliferative activity with little toxicity to normal tissues.

Anterior thigh compartment syndrome after prone positioning for lumbosacral fixation.

We report a case of a patient who developed anterior thigh compartment syndrome after being positioned prone for instrumented lumbar spine surgery. Although rare, clinicians should be aware that compartment syndrome is a possible complication of spinal surgery.

Drug absorption by the respiratory mucosa: cell culture models and particulate drug carriers.

The inhalation route is of increasing interest for both local and systemic drug delivery, including macromolecular biopharmaceuticals, such as peptides, proteins, and gene therapeutics. In addition to appropriate aerosolization for deposition in relevant areas of the respiratory tract, therapeutic molecules may require an advanced carrier system for safe and efficient delivery to their target. Two approaches to obtain novel carrier systems for pulmonary drug delivery are large porous microparticles with a low aerodynamic diameter and lectin-functionalized liposomes. Epithelial cells of alveolar or bronchial origin, obtained either from patient material or from established cell lines, can be grown on permeable filter supports, resulting in polarized monolayers with functional intercellular junctions. With such in vitro models, transport of drugs into pulmonary epithelial cells and/or across the air-blood barrier, as well as the effect and efficacy of novel drug carrier systems can be systematically studied.

Lectin-functionalized liposomes for pulmonary drug delivery: interaction with human alveolar epithelial cells.

In this study the interaction of lectin-functionalized liposomes with two different alveolar epithelial cell culture models was evaluated. Plant lectins were coupled to liposomes exploiting the avidin/biotin technology. In contrast to lectin-free liposomes, lectin functionalized liposomes specifically bound to A549 cells, a tumor-derived cell line. Using this cell line, temperature-dependent binding assays as well as confocal laser scanning microscopy (CLSM) revealed that the lectin liposomes were only bound but not taken up by these cells. In contrast to these findings, confocal images of human alveolar epithelial cells in primary culture incubated together with lectin liposomes indicated binding as well as cellular uptake. Fluorescein-isothiocyanate (FITC)-labeled dextrans (Mw 40,000 Da), encapsulated in lectin-functionalized liposomes and incubated with monolayers of primary cultured human alveolar epithelial cells appeared to be localized intracellularly by CLSM. This suggests that lectin-mediated bioadhesion and uptake of liposomal carriers may provide a useful technology for improved delivery of hydrophilic macromolecules to the alveolar epithelium.

Lectin-functionalized liposomes for pulmonary drug delivery: effect of nebulization on stability and bioadhesion.

The generation of respirable aerosols of a functionalized colloidal carrier has been investigated in this study. Lectin-functionalized liposomes, which proved to show improved cell association (using A549 cell line and primary human alveolar cells) even in the presence of a commercial lung surfactant preparation, have been developed. The stability of non-functionalized liposomes during nebulization using a jet nebulizer (Pari II provocation nebulizer, operated using an air flow of 30 l/min) was firstly investigated, and the experimental and formulation conditions were optimized and applied for the preparation of lectin-functionalized liposomes. The incorporation of cholesterol enhanced the stability of the liposomes during nebulization (from 15-20% leakage of a hydrophilic marker to 8% upon cholesterol incorporation) and upon incubation with lung surfactant preparation. Nebulization of the functionalized liposomes did not significantly influence their physical stability. Their enhanced cell binding capability (compared to non-functionalized liposomes) was also maintained. A drop in cell association compared to fresh functionalized liposomes was detected after nebulization, nevertheless, the binding was still significantly higher than that of the non-functionalized liposomes. The deposition of the liposomal preparation in lung periphery, proved by the deposition of the liposomal preparation on the lower stages of an ASTRA type cascade impinger and a mean median aerodynamic diameter (MMAD) of 2.85 microm, makes it a potential candidate as a macromolecule-drug carrier for local and/or systemic administration.

Análise crítica da terapêutica insulínica: dificuldades a serem resolvidas em diferentes níveis de atençäo à saúde / Critical analysis of insulinic therapy: dificulties to be solved in different health care levels

Após os animadores resultados do DCCT, a terapêutica insulínica intensiva tem sido recomendada indistintamente em todos os países. Em nossa experiência, aplicada à população de pacientes diabéticos em uso de insulina, atendidos no Hospital Universitário da PCCAMP, tal esquema se mostrou inviável e inadequado, a despeito de contarmos com o atendimento multiprofissional recomendado à assistência do paciente diabético. As razões socioeconômicas e culturais constituíram o principal fator limitante a esta prática. Devido a isto utilizamos em nosso serviço um esquema terapêutico adaptado, que denominamos "insulinização por etapas, através de doses duplas combinadas". Tal método foi o que mostrou melhores resultados devido à fácil inteligibilidade, e porque atribui responsabilidades ao paciente quanto aos resultados a serem obtidos. Desta forma, entre 50 pacientes em uso de insulina, obtivemos sessenta e quatro por cento de bom controle em um tempo médio de seguimento ambulatorial semanal que durou oito semanas. Os pacientes com mau controle glicêmico (trinta e sies por cento) foram reanalisados, caso, para correção das possíveis causas. A casuística final computou oitenta e seis por cento de bom controle glicêmico, sendo que em quatorze por cento dos casos este objetivo não foi alcançado. Entendemos, que algumas das causas de mau controle glicêmicosão de fácil detecção e podem ser corrigidos em nível primário de atenção à saúde. Entretanto, outras causas bastante complexas que dificultam o controle deverão ser referendadas aos setores secundários e terciário de atendimento, visando propiciar o controle glicêmico ótimo a todos os pacientes diabéticos

Evaluation of fast disintegrants in terfenadine tablets containing a gas-evolving disintegrant.

Effects of four fast disintegrants on the dissolution of terfenadine tablets containing the gas-evolving disintegrant, CaCO3, were evaluated. In addition, effects of presence of starch along with the fast disintegrants on the dissolution of the tablets were examined. Dissolution data were treated to give dissolution parameters which reflected efficiency of the disintegrant combinations. The four fast disintegrants improved disintegration/dissolution of the original formulation. The relative efficiency of improvement was in the order crospovidone > Ac-Di-Sol > Primojel > low substituted hydroxypropylcellulose. The presence of starch advertently affected the role of the fast disintegrants. Scanning electron microscope studies revealed that starch covered the drug-containing granules and other particles of the tablet. pH changes during dissolution of representative tablets in 0.1 N HCl solutions were determined at specific time intervals. The progressive decrease in rates of acid consumption as a function of the amount of starch, along with the SEM studies, suggested that a barrier existed around the tablet particles. The barrier was generated by the swelled starch grains and was responsible for the loss of the dissolution-improving capacity of the fast disintegrants. Furthermore, the barrier interfered with the diffusion of the hydronium ions and therefore, impaired the function of the disintegrant combination.