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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

Bacterial and quantum dot deposition. a Murine lung section showing intranasal F. novicida (red) in alveoli. b Size distribution of nanoaerosolized quantum dots. c Quantum dots delivered intranasally are mainly deposited in the bronchioles and lining mucus. d Quantum dot delivered via nanoaerosol penetrate the alveoli and deposit throughout the lung
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Fig2: Bacterial and quantum dot deposition. a Murine lung section showing intranasal F. novicida (red) in alveoli. b Size distribution of nanoaerosolized quantum dots. c Quantum dots delivered intranasally are mainly deposited in the bronchioles and lining mucus. d Quantum dot delivered via nanoaerosol penetrate the alveoli and deposit throughout the lung

Mentions: Previous studies show that Francisella targets alveolar type II epithelial cells and macrophages during pulmonary infections so the ability to deliver therapeutics directly to the alveoli would be beneficial [24–26]. Intranasal delivery of F. novicida to the lungs was verified to result in localization of bacteria in the alveoli (Fig. 2a). According to MPPD, the small size of nanoaerosols allow for deeper penetration into the lung, specifically to the alveoli. To evaluate this claim, quantum dots were used to trace deposition in the lungs following nanoaerosol exposure and intranasal instillation. Quantum dots are nanocrystals made of semiconducting material ~20 nm in diameter that fluoresce at specified wavelengths and are frequently used as labels [27]. As seen in Fig. 2b, the nanoaerosol generator produced nanoaerosolized particles with a geometric mean diameter of 39 nm, which confirms that the generator is capable of producing particles in the nano-sized range. As predicted, sections of the lungs treated with nanoaerosolized quantum dots show that, when compared to intranasal delivery, particles homogenously penetrate deeper into the lower respiratory tract, including the alveoli and lung parenchyma, instead of mostly being deposited in the bronchioles and mucus (Fig. 2c, d).Fig. 2


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)

Bacterial and quantum dot deposition. a Murine lung section showing intranasal F. novicida (red) in alveoli. b Size distribution of nanoaerosolized quantum dots. c Quantum dots delivered intranasally are mainly deposited in the bronchioles and lining mucus. d Quantum dot delivered via nanoaerosol penetrate the alveoli and deposit throughout the lung
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Bacterial and quantum dot deposition. a Murine lung section showing intranasal F. novicida (red) in alveoli. b Size distribution of nanoaerosolized quantum dots. c Quantum dots delivered intranasally are mainly deposited in the bronchioles and lining mucus. d Quantum dot delivered via nanoaerosol penetrate the alveoli and deposit throughout the lung
Mentions: Previous studies show that Francisella targets alveolar type II epithelial cells and macrophages during pulmonary infections so the ability to deliver therapeutics directly to the alveoli would be beneficial [24–26]. Intranasal delivery of F. novicida to the lungs was verified to result in localization of bacteria in the alveoli (Fig. 2a). According to MPPD, the small size of nanoaerosols allow for deeper penetration into the lung, specifically to the alveoli. To evaluate this claim, quantum dots were used to trace deposition in the lungs following nanoaerosol exposure and intranasal instillation. Quantum dots are nanocrystals made of semiconducting material ~20 nm in diameter that fluoresce at specified wavelengths and are frequently used as labels [27]. As seen in Fig. 2b, the nanoaerosol generator produced nanoaerosolized particles with a geometric mean diameter of 39 nm, which confirms that the generator is capable of producing particles in the nano-sized range. As predicted, sections of the lungs treated with nanoaerosolized quantum dots show that, when compared to intranasal delivery, particles homogenously penetrate deeper into the lower respiratory tract, including the alveoli and lung parenchyma, instead of mostly being deposited in the bronchioles and mucus (Fig. 2c, d).Fig. 2

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