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Nanoaerosols reduce required effective dose of liposomal levofloxacin against pulmonary murine Francisella tularensis subsp. novicida infection.

Propst CN, Nwabueze AO, Kanev IL, Pepin RE, Gutting BW, Morozov VN, van Hoek ML - J Nanobiotechnology (2016)

Bottom Line: Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida.In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes.This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.

View Article: PubMed Central - PubMed

Affiliation: School of Systems Biology and National Center for Biodefense and Infectious Diseases, George Mason University, MS1H8, Manassas, VA, 20110, USA.

ABSTRACT

Background: The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator. This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. novicida (F. novicida) infections in BALB/c mice.

Results: First, the analysis of quantum dots distribution in cryosections of murine lungs demonstrated that nanoaerosols penetrate the alveoli and spread more homogenously in the lungs than upon intranasal delivery. Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida. The generator was capable of delivering a sufficient dose of nanoaerosolized liposome-encapsulated levofloxacin to rescue mice against 100LD50 of F. novicida.

Conclusions: The nanoaerosol-delivered dosage of liposome-encapsulated levofloxacin required to rescue mice is approximately 94× lower than the oral required dose and approximately 8× lower than the intraperitoneal dose required for rescue. In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes. This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.

No MeSH data available.


Related in: MedlinePlus

Levofloxacin delivered as nanoaerosol and standard aerosol. a Size distribution of nanoaerosolized levofloxacin generated from a 4 mg/mL levofloxacin solution in water. b Survival curve of mice treated with nanoaerosolized levofloxacin (blue) against 100LD50 intranasal F. novicida infection. c Survival curve of mice treated with 3-jet Collison nebulizer aerosolized levofloxacin (30 min—red, 1 h—green, 2 h—blue) against 100LD50 intranasal F. novicida infection
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Fig3: Levofloxacin delivered as nanoaerosol and standard aerosol. a Size distribution of nanoaerosolized levofloxacin generated from a 4 mg/mL levofloxacin solution in water. b Survival curve of mice treated with nanoaerosolized levofloxacin (blue) against 100LD50 intranasal F. novicida infection. c Survival curve of mice treated with 3-jet Collison nebulizer aerosolized levofloxacin (30 min—red, 1 h—green, 2 h—blue) against 100LD50 intranasal F. novicida infection

Mentions: While quantum dots are a good demonstrative tool, this data is only qualitative in nature and the use of nanoaerosols as therapeutics still requires detailed evaluation. F. tularensis is a biothreat agent that is known to be susceptible to treatment with levofloxacin, among other antibiotics [14–17]. Figure 3a shows that the ESN generator is capable of nanoaerosolizing a 4 mg/mL levofloxacin solution in water, producing particles with a geometric mean diameter of 56 nm. The MPPD model predicts a total deposition of 43.5 % for particles of this size: 17.8 % alveolar, 10.3 % tracheobronchial, and 15.4 % nasal (Fig. 1). Since deposition is a physical process that relies on diffusion and impaction, the size of the nanoaerosolized particles will have a similar regional deposition pattern despite the substance or the presence of a complex internal structure being delivered. Since the deposition of the nanoaerosolized quantum dots in the previous experiment supported the MPPD model, a traceable antibiotic was not used. Two additional small peaks with the mode diameters of 150 and 280 nm are present in the size distribution histogram and are most likely the result of particle coagulation.Fig. 3


Nanoaerosols reduce required effective dose of liposomal levofloxacin against pulmonary murine Francisella tularensis subsp. novicida infection.

Propst CN, Nwabueze AO, Kanev IL, Pepin RE, Gutting BW, Morozov VN, van Hoek ML - J Nanobiotechnology (2016)

Levofloxacin delivered as nanoaerosol and standard aerosol. a Size distribution of nanoaerosolized levofloxacin generated from a 4 mg/mL levofloxacin solution in water. b Survival curve of mice treated with nanoaerosolized levofloxacin (blue) against 100LD50 intranasal F. novicida infection. c Survival curve of mice treated with 3-jet Collison nebulizer aerosolized levofloxacin (30 min—red, 1 h—green, 2 h—blue) against 100LD50 intranasal F. novicida infection
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835885&req=5

Fig3: Levofloxacin delivered as nanoaerosol and standard aerosol. a Size distribution of nanoaerosolized levofloxacin generated from a 4 mg/mL levofloxacin solution in water. b Survival curve of mice treated with nanoaerosolized levofloxacin (blue) against 100LD50 intranasal F. novicida infection. c Survival curve of mice treated with 3-jet Collison nebulizer aerosolized levofloxacin (30 min—red, 1 h—green, 2 h—blue) against 100LD50 intranasal F. novicida infection
Mentions: While quantum dots are a good demonstrative tool, this data is only qualitative in nature and the use of nanoaerosols as therapeutics still requires detailed evaluation. F. tularensis is a biothreat agent that is known to be susceptible to treatment with levofloxacin, among other antibiotics [14–17]. Figure 3a shows that the ESN generator is capable of nanoaerosolizing a 4 mg/mL levofloxacin solution in water, producing particles with a geometric mean diameter of 56 nm. The MPPD model predicts a total deposition of 43.5 % for particles of this size: 17.8 % alveolar, 10.3 % tracheobronchial, and 15.4 % nasal (Fig. 1). Since deposition is a physical process that relies on diffusion and impaction, the size of the nanoaerosolized particles will have a similar regional deposition pattern despite the substance or the presence of a complex internal structure being delivered. Since the deposition of the nanoaerosolized quantum dots in the previous experiment supported the MPPD model, a traceable antibiotic was not used. Two additional small peaks with the mode diameters of 150 and 280 nm are present in the size distribution histogram and are most likely the result of particle coagulation.Fig. 3

Bottom Line: Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida.In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes.This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.

View Article: PubMed Central - PubMed

Affiliation: School of Systems Biology and National Center for Biodefense and Infectious Diseases, George Mason University, MS1H8, Manassas, VA, 20110, USA.

ABSTRACT

Background: The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator. This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. novicida (F. novicida) infections in BALB/c mice.

Results: First, the analysis of quantum dots distribution in cryosections of murine lungs demonstrated that nanoaerosols penetrate the alveoli and spread more homogenously in the lungs than upon intranasal delivery. Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida. The generator was capable of delivering a sufficient dose of nanoaerosolized liposome-encapsulated levofloxacin to rescue mice against 100LD50 of F. novicida.

Conclusions: The nanoaerosol-delivered dosage of liposome-encapsulated levofloxacin required to rescue mice is approximately 94× lower than the oral required dose and approximately 8× lower than the intraperitoneal dose required for rescue. In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes. This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.

No MeSH data available.


Related in: MedlinePlus