Evaluation of factors affecting size and size distribution of chitosan-electrosprayed nanoparticles

Background: Size and size distribution of polymeric nanoparticles have important effect on their properties for pharmaceutical application. In this study, Chitosan nanoparticles were prepared by electrospray method [electrohydrodynamic atomization] and parameters that simultaneously affect size and/or size distribution of chitosan nanoparticles were optimized

Methods: Effect of formulation/processing three independent formulation/processing parameters, namely concentration, flow rate and applied voltage was investigated on particle size and size distribution of generated nanoparticles using a Box-Behnken experimental design

Results: All the studied factors showed important effects on average size and size dis-tribution of nanoparticles. A decrease in size and size distribution was obtainable with decreasing flow rate and concentration and increasing applied voltage. Eventually, a sample with minimum size and polydispersity was obtained with polymer concentration, flow rate and applied voltage values of 0.5 %w/v, 0.05 ml/hr and 15 kV, respectively. The experimentally prepared nanoparticles, expected having lowest size and size distribution values had a size of 105 nm, size distribution of 36 and Zeta potential of 59.3 mV

Conclusion: Results showed that optimum condition for production of chitosan nano-particles with the minimum size and narrow size distribution was a minimum value for flow rate and highest value for applied voltage along with an optimum chitosan concentration

Evaluation of a nanosuspension formulation prepared through microfluidic reactors for pulmonary delivery of budesonide using nebulizers

This study aimed to determine the aerosolization behavior of a nanodispersion of budesonide, prepared using microfluidic reactors. The size and morphology of budesonide nanoparticles were characterized by photon correlation spectroscopy [PCS] and transmission electron microscopy [TEM]. Processing/formulation parameters for formation of the nanoparticles were studied to determine their effects on the particle size. Results showed a narrow distribution for budesonide nanodispersion with spherical and smooth surfaced particles. To investigate the in-vitro aerosolization performance of the nanodispersion, the preparation was compared with a commercially available budesonide microsuspension using the Comite Europeen Normalization [CEN] methodology. Aerosolization results showed that the fine particle fraction [FPF] generated from the budesonide nanodispersion was significantly higher than that of the marketed budesonide [ie. mean [SD] 56.88 [3.37]% vs. 38.04 [7.82]%, respectively]. Additionally, mass median aerodynamic diameter [MMAD] of nano-budesonide dispersion was significantly smaller than the microsuspension [i.e. mean [SD] 3.91 [0.49] vs. 6.22 [1.09] microm, respectively], with nebulization time of nano-budesonide dispersion significantly shorter than the marketed budesonide microsuspension [i.e. 12.3 [0.37] vs. 14.85 [0.36] min, respectively]. The produced nanodispersion was found to be stable over a period of 10 days if stored at 4 °C

Use of artificial neural networks to examine parameters affecting the immobilization of streptokinase in chitosan

Streptokinase is a potent fibrinolytic agent which is widely used in treatment of deep vein thrombosis [DVT], pulmonary embolism [PE] and acute myocardial infarction [MI]. Major limitation of this enzyme is its short biological half-life in the blood stream. Our previous report showed that complexing streptokinase with chitosan could be a solution to overcome this limitation. The aim of this research was to establish an artificial neural networks [ANNs] model for identifying main factors influencing the loading efficiency of streptokinase, as an essential parameter determining efficacy of the enzyme. Three variables, namely, chitosan concentration, buffer pH and enzyme concentration were considered as input values and the loading efficiency was used as output. Subsequently, the experimental data were modeled and the model was validated against a set of unseen data. The developed model indicated chitosan concentration as probably the most important factor, having reverse effect on the loading efficiency

Toxicity assessment of nanosilver wound dressing in Wistar rat

Antibiotic resistance to microorganisms is one of the major problems faced in the field of wound care in burns patients. Silver nanoparticles have come up as potent antimicrobial agent and are being evaluated in diverse medical applications ranging from silver based dressings to silver coated medical devices. We aimed in present study to test the release of nanosilver from nanosilver wound dressing and compare the dermal and systemic toxicity of nanosilver dressings in a repeated dose [21 days] model. Under general anesthesia, a limited standard 2nd degree burns were provided on the back of each rat in all treatment, negative control [simple dressing] and 5% silver nitrate groups, each contained 5 male wistar rats. According to the analysis made by atomic absorption spectrometry, the wound dressings released 0.599 +/- 0.083 ppm of nanosilver during first 24 hrs of study. Daily observations were recoded and wounds were covered with new dressings each 24 hrs. Burn healing was observed in nanosilver wound dressing group in shorter time periods than the control groups. In toxicity assessment, this dressing didn't cause any hematological and histopathological abnormalities in treatment group but biochemical studies showed significant rise of plasma transaminase [ALT] at the endpoint [21 days] of the study [P=0.027]. Portal mononuclear lymphoid and polymorphonuclear leukocyte infiltrations in three to four adjacent foci were recognized around the central hepatic vein in treatment group. Mild hepatotoxic effects of nanosilver wound dressing in wistar rat emphasize the necessity of more studies on toxicity potentials of low dose nanosilver by dermal applications