Novel Formulation of Large Hollow Nanoparticles Aggregates as Potential Carriers in Inhaled Delivery of Nanoparticulate Drugs
Institute of Chemical and Engineering Sciences, Singapore 627833, and Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 119260
Ind. Eng. Chem. Res., 2006, 45 (10), pp 3697–3706
Ind. Eng. Chem. Res., 2006, 45 (10), pp 3697–3706
A novel formulation technique to manufacture large hollow carrier particles of nanoparticulate drugs for inhaled drug delivery is developed in the present work. The large hollow carrier particles, whose shells are composed of nanoparticles aggregates, are manufactured via the spray drying of nanoparticulate suspensions under a predetermined operating condition. The large and hollow features of the carrier particles (dg ≈ 10 μm; ρe 1 g/cm3) are purposely formulated to produce carrier particles that have high flowability and high therapeutic efficacy, which are crucial for a successful drug delivery to the lungs. Polyacrylate and silica nanoparticles of various sizes (5−150 nm), without loaded drugs, are used as the model nanoparticles. The focus of the present work is to investigate the effects of size, chemical nature, and feed concentration of the nanoparticles on the morphology and degree of hollowness of the spray-dried carrier particles. The chemical nature of the nanoparticles, not the size, is observed to be the determining factor in the hollow particle formation, as evident in the varying results of the effects of changing the concentration among nanoparticles of different chemical nature. for full article / detailed reading please visit link : http://pubs.acs.org/doi/abs/10.1021/ie0513191
Abstract 2-
Subchronic Inhalation Toxicity of Silver Nanoparticles
Toxicological SciencesVolume 108, Number 2 Pp. 452-461
The subchronic inhalation toxicity of silver nanoparticles was studied in Sprague-Dawley rats. Eight-week-old rats, weighing approximately 253.2 g (males) and 162.6 g (females), were divided into four groups (10 rats in each group): fresh-air control, low dose (0.6 x 106 particle/cm3, 49 µg/m3), middle dose (1.4 x 106 particle/cm3, 133 µg/m3), and high dose (3.0 x 106 particle/cm3, 515 µg/m3). The animals were exposed to silver nanoparticles (average diameter 18–19 nm) for 6 h/day, 5 days/week, for 13 weeks in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and pulmonary function tests were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and the organ weights were measured. Bile-duct hyperplasia in the liver increased dose dependently in both the male and female rats. Histopathological examinations indicated dose-dependent increases in lesions related to silver nanoparticle exposure, including mixed inflammatory cell infiltrate, chronic alveolar inflammation, and small granulomatous lesions. Target organs for silver nanoparticles were considered to be the lungs and liver in the male and female rats. No observable adverse effect level of 100 µg/m3 is suggested from the experiments. For detailed reading please visit link : http://toxsci.oxfordjournals.org/cgi/content/abstract/kfn246
Abstract 3-
Possible toxic damage from inhaled nano particles :
The Medical news,27. October 2005 05:18
The small size of nanoparticles in the size range 5-100 nm gives many novel and useful properties and they are used in applications as diverse as face creams, plastics, medical imaging, novel drug therapies and magnetic recording. Such particles are increasingly manufactured and released into the environment on industrial scales.
The small size of nanoparticles in the size range 5-100 nm gives many novel and useful properties and they are used in applications as diverse as face creams, plastics, medical imaging, novel drug therapies and magnetic recording. Such particles are increasingly manufactured and released into the environment on industrial scales.
However, there is growing concern that the very same properties that make them so useful may also lead to enhanced toxicity if the particles are breathed in. The particles are so small - 100,000 particles laid end-to-end would only stretch a few millimetres - that it is not clear how the body's normal defence mechanisms will cope with them.
By harnessing their combined expertise in physics and medicine, Dr Paul Howes, Department of Physics & Astronomy, and Dr Jonathan Grigg, Department of Infection, Immunity and Inflammation, will research possible toxic damage from inhaled nanoparticles.
Dr Howes and Dr Grigg will produce macrophages from human blood monocytes and expose them, in vitro, to an aerosol of metal nanoparticles, measuring any toxic damage to their DNA. Precise control over the size, chemical composition and dose of particles with enable them to determine whether there is a correlation between size and toxicity. The potential for genotoxicity (and therefore increased vulnerability to lung cancer) is an important factor when setting national air quality guidelines for particles. It is envisaged that this exposure technique, which more closely mimics "real life" exposure, will allow genotoxicity to be assessed for a wide range of manufactured nanoparticles.
Monocyte-derived macrophages were chosen since airway macrophages are a part of the body's immune system and normally reside deep in the lungs where they form the first line of defence against inhaled particles. For further reading please visit link :
Abstract 4 -
Production of nanoparticles for inhalation drug delivery-
Nano science and Nano technology cluster 15 may 2009,
Sodium chloride aerosols have been widely used as part of bronchial provocation tests to identify people with active asthma, exercised-induced asthma, and those who wish to enter particular occupations (e.g. police, army) or sports (e.g. diving). When sodium chloride is inhaled into the airways they increase the osmolarity of the fluid lining the mucosal surfaces. The bronchial muscle of an asthmatic will then contract with response to the rate of change of osmolarity.
The results of a rigorous experimental investigation on the effect of various parameters affecting the production of nanocrystals are presented. The experiments are conducted in a 1-L jacketed crystalliser. The sonication is induced by way of a sonication probe immersed into the crystallisation suspension. Temperature is controlled by a heating/cooling system. A concentrated solution of NaCl is crystallised with the use of ethanol as the antisolvent. Emphasis is laid on sonification intensity and temperature. The results indicated that optimal conditions exist that minimise the size of the crystals towards the nano range. Future work will assess solution concentration, feed rate and sonication time. The results will provide clear guidance for the subsequent step of process model development and thence process optimisation. For further reading please visit link.
Abstract 5-
Nano particles - health impacts
Pulmonary toxicity studies in rats demonstrate that lung exposures to ultrafine or nanoparticles produce greater adverse inflammatory responses compared with larger particles of identical composition at equivalent mass concentrations. Surface properties (particularly surface area) and free radical generation by the interaction of particles with cells appear to play important roles in nanoparticle toxicity.
Contributing to these effects is the very high size specific deposition of nanoparticles when inhaled as singlet rather than aggregated particles. Some evidence suggests that inhaled ultrafine or nanoparticles, following deposition in the lung, largely escape alveolar macrophage surveillance and gain access to the pulmonary interstitium, a potentially vulnerable anatomical compartment. Results from the limited toxicological database have fostered the perception that all nanoparticles are toxic.
For further reading please visit link : http://www.materialstoday.com/pdfs_7_2/warheit.pdf
Abstract 5
Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alta., T6G 2N8, CANADA
Regional drug delivery via dry powder inhalers offers many advantages in the management of pharmaceutical compounds for the prevention and treatment of respiratory diseases. In the present study, doxorubicin (DOX)-loaded nanoparticles were incorporated as colloidal drug delivery system into inhalable carrier particles using a spray-freeze-drying technique. The cytotoxic effects of free DOX, carrier particles containing blank nanoparticles or DOX-loaded nanoparticles on H460 and A549 lung cancer cells were assessed using a colorimetric XTT cell viability assay. The mean geometric carrier particle size of 10 ± 4 μm was determined using confocal laser scanning microscopy. DOX-loaded nanoparticles had a particle size of 173 ± 43 nm after re-dissolving of the carrier particles. Compared to H460 cells, A549 cells showed less sensitivity to the treatment with free DOX. The DOX-nanoparticles showed in both cell lines a higher cytotoxicity at the highest tested concentration compared to the blank nanoparticles and the free DOX. The cell uptake of free DOX and DOX delivered by nanoparticles was confirmed using confocal laser scanning microscopy. This study supports the approach of lung cancer treatment using nanoparticles in dry powder aerosol form.
Journal TitleInternational journal of pharmaceutics , 2006, vol. 319, no1-2, pp. 155-161
For further reading please visit link : http://cat.inist.fr/?aModele=afficheN&cpsidt=17989248
Abstract 6-
NANO PARTICLE HEALTH AND SAFETY
Nanotechnology is the engineering and manipulation of materials at the molecular level. This new technology creates materials with dimensions ranging from 1 to 100 nanometers (1 nanometer is 1 billionth of a meter). Particles created at the nanoscale have different chemical and physical properties than larger particles of the same material. These manufactured nanoparticles are known as engineered nanoparticles.*
Nanotechnology is the engineering and manipulation of materials at the molecular level. This new technology creates materials with dimensions ranging from 1 to 100 nanometers (1 nanometer is 1 billionth of a meter). Particles created at the nanoscale have different chemical and physical properties than larger particles of the same material. These manufactured nanoparticles are known as engineered nanoparticles.*
Scientists and manufacturers can use nanoparticles to create new products that would be impossible with larger particles.
* Engineered nanoparticles are referred to as nanoparticles throughout this webpage. USEPA “Nanotechnology White Paper”: http://www.epa.gov/osa/nanotech.htm
National Institute for Occupational Safety and Health (NIOSH)
NIOSH is the leading federal agency conducting research and providing guidance on the occupational safety and health implications and applications of nanotechnology. This research focuses NIOSH’s scientific expertise, and its efforts, on answering the questions that are essential to understanding these implications and applications:
How might workers be exposed to nano-sized particles in the manufacturing or industrial use of nanomaterials?
How do nanoparticles interact with the body’s systems?
Little information is available about the hazards of nanoparticles in the workplace. NIOSH is conducting research to determine whether they pose a health threat to exposed workers.
Different types of nanoparticles are made or used in various industrial processes. To determine whether these nanoparticles pose a hazard to workers, scientists must know the following:
Types and concentrations of nanoparticles in the workplace.
Properties of nanoparticles that could affect the body.
Concentrations of nanoparticles that could produce adverse effects.
Effects in animals, laboratory studies in animals have shown that when some types of nanoparticles are inhaled, they may reach the blood, brain, and other organs of laboratory animals when they are inhaled. Some studies have shown adverse effects such as inflammation and fibrosis in the lungs and other organs of animals.
Effects in humans:
Human studies of exposure and response to engineered nanoparticles are not currently available.
Safety issues in the workplaceFire and explosion are the main safety hazards associated with nanoparticles in the workplace. Some materials at the nanometer scale may unexpectedly become chemical catalysts and result in unanticipated reactions.
Current exposure standards No U.S. or international exposure standards have been established for nanoparticles.
Although more research is needed to predict the effects of nanoparticle exposures in humans, sufficient information is available to provide interim recommendations and guidance about occupational exposures to nanoparticles. NIOSH recommends a prudent approach for manufacturing and using nanoparticles in industry.
Employers should take steps to minimize worker exposures until more information is available.
OccupationalHazards :http://www.occupationalhazards.com/News/Article/78224/EPA_Program_Addresses_Nanoscale_Product_Safety.aspx
OccupationalHazards :http://www.occupationalhazards.com/News/Article/78224/EPA_Program_Addresses_Nanoscale_Product_Safety.aspx
Routes of Exposure-
Workers may be exposed by three routes:
Inhalation - The most common route of exposure is by inhalation - breathing in airborne particles into the lungs and respiratory system.
Ingestion - Workers can be exposed by unintentional hand-to-mouth transfer of materials or swallowing particles cleared from the respiratory tract.
Absorption - Some studies mention that nanoparticles may penetrate the skin. This possibility is being investigated.
Several factors affect worker exposure to nanoparticles:
The concentration, duration, and frequency of exposure to nanoparticles all affect exposure.
The ability of nanoparticles to be easily dispersed as a dust (e.g. a powder) or an airborne spray or droplets may result in greater worker exposure.
Use of protective measures such as engineering controls (e.g. fume hoods) and personal protective equipment (e.g. gloves) can reduce worker exposure.
Job-related activities may also influence worker exposure:
Active handling of nanoparticles as powders in non-enclosed systems pose the greatest risk for inhalation exposure.
Tasks that generate aerosols of nanoparticles from slurries, suspensions, or solutions pose a potential for inhalation and dermal exposure.
Cleanup and disposal of nanoparticles may result in exposure if not properly handled.
Maintenance and cleaning of production systems or dust collection systems may result in exposure if deposited nanoparticles are disturbed.
Machining, sanding, drilling, or other mechanical disruptions of materials containing nanoparticles may lead to aerosolization of nanoparticles.
Measurement of Nanoparticles-
Measurement of Nanoparticles-
Traditional industrial hygiene sampling methods can be used to measure airborne nanoparticles. However, these methods are limited and require careful interpretation. Scientists are developing more sensitive and specific sampling techniques to evaluate occupational exposures to nanoparticles.
Sampling in the workplace should include background measurements and measurements before, during, and after production or handling of nanoparticles. These measurements can determine if emissions and possible exposures are occurring.
Exposure Controls-
Engineering controls should be used to reduce worker exposures to nanoparticles. These controls include source enclosure (isolating the generation source from the worker) and local exhaust ventilation systems. Exhaust ventilation systems that use high-efficiency particulate air (HEPA) filters are very effective in removing nanoparticles.
Engineering controls have been designed to reduce worker exposures to other particles with sizes similar to those of nanoparticles. Examples include controls for welding fumes. These controls are also effective for the manufacturing and fabrication of nanoparticles.
RespiratorsRespirators should be considered if engineering and administrative controls do not control worker exposures to nanoparticles. The decision to use respirators should be based on professional judgment and an assessment of worker exposures and the health risks they pose.
TrainingWorker training should be part of any complete safety and health program. To reduce nanoparticle exposures, workers should learn how to safely handle nanoparticles, use personal protective equipment, handle work clothes, clean contaminated surfaces, and dispose of spilled nanoparticles.
This information is modeled after NIOSH Publication No. 2008-112: Safe Nanotechnology in the Workplace.
Acknowledgment: Based on NIOSH Publication 2008-112. For further reading please visit link :
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