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Biodegradable Janus nanoparticles for local pulmonary delivery of hydrophilic and hydrophobic molecules to the lungs.

Garbuzenko OB, Winkler J, Tomassone MS, Minko T - Langmuir (2014)

Bottom Line: Nanoparticles with dual load were used for their local inhalation delivery directly to the lungs of mice with orthotopic model of human lung cancer.In vivo experiments showed that the selected nanoparticles with two anticancer drugs with different mechanisms of action prevented progression of lung tumors.It should be stressed that anticancer effects of the combined treatment with two anticancer drugs loaded in the same nanoparticle significantly exceeded the effect of either drug loaded in similar nanoparticles alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey University , 160 Frelinghuysen Rd., Piscataway, New Jersey 08854, United States.

ABSTRACT
The aim of the present work is to synthesize, characterize, and test self-assembled anisotropic or Janus particles designed to load anticancer drugs for lung cancer treatment by inhalation. The particles were synthesized using binary mixtures of biodegradable and biocompatible materials. The particles did not demonstrate cyto- and genotoxic effects. Janus particles were internalized by cancer cells and accumulated both in the cytoplasm and nuclei. After inhalation delivery, nanoparticles accumulated preferentially in the lungs of mice and retained there for at least 24 h. Two drugs or other biologically active components with substantially different aqueous solubility can be simultaneously loaded in two-phases (polymer-lipid) of these nanoparticles. In the present proof-of-concept investigation, the particles were loaded with two anticancer drugs: doxorubicin and curcumin as model anticancer drugs with relatively high and low aqueous solubility, respectively. However, there are no obstacles for loading any hydrophobic or hydrophilic chemical agents. Nanoparticles with dual load were used for their local inhalation delivery directly to the lungs of mice with orthotopic model of human lung cancer. In vivo experiments showed that the selected nanoparticles with two anticancer drugs with different mechanisms of action prevented progression of lung tumors. It should be stressed that anticancer effects of the combined treatment with two anticancer drugs loaded in the same nanoparticle significantly exceeded the effect of either drug loaded in similar nanoparticles alone.

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Distribution of anisotropic biodegradable polymer/lipidJanus nanoparticlesin different organs 1 and 24 h after intravenous or inhalation administrations.Mean values for eight animals are presented.
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fig5: Distribution of anisotropic biodegradable polymer/lipidJanus nanoparticlesin different organs 1 and 24 h after intravenous or inhalation administrations.Mean values for eight animals are presented.

Mentions: A Collison nebulizer connected tofour-port, nose-only exposure chambers was used for inhalation deliveryof drug-loaded nanoparticles. The measurement of nanoparticle sizeshowed that nebulization did not influence significantly on the sizeand stability of nanoparticles (Figure 2).The results presented on Figure 5 revealedthat 1 h after intravenous administration the distribution patternsof 155 nm (Figure 5a) and 450 nm (Figure 5b) Janus nanoparticles were similar to the preferentialparticle accumulation in mouse liver. However, slightly higher accumulationin the lungs was found for the larger nanoparticles. One hour afterinhalation delivery, nanoparticles of both sizes were detected inthe lungs (Figure 5c,d); however, the accumulationof nanoparticles with 450 nm in diameter was twice higher when comparedwith 155 nm nanoparticles. The analysis of the distribution profileof Janus nanoparticles 24 h after their intravenous administrationsshowed that the majority of nanoparticles of both sizes were foundin the liver and kidneys, while no fluorescent signal was detectedin lungs (Figure 5e,f). As was mentioned above,the accumulation of larger nanoparticles in the lungs 1 h after treatmentwas substantially higher when compared with smaller nanoparticles(Figure 5c,d). However, 24 h after inhalation,similarly to the intravenous administration, the 155 nm nanoparticleswere found only in the liver and kidneys (Figure 5g). In contrast, larger nanoparticles were still detectedin the lungs 24 h after inhalation and their content was comparablewith that after 1 h after treatment (Figure 5d, h). On the basis of these results we selected Janus nanoparticleswith the size of 450 nm for further inhalation treatment of mice withorthotopic lung cancer.


Biodegradable Janus nanoparticles for local pulmonary delivery of hydrophilic and hydrophobic molecules to the lungs.

Garbuzenko OB, Winkler J, Tomassone MS, Minko T - Langmuir (2014)

Distribution of anisotropic biodegradable polymer/lipidJanus nanoparticlesin different organs 1 and 24 h after intravenous or inhalation administrations.Mean values for eight animals are presented.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222657&req=5

fig5: Distribution of anisotropic biodegradable polymer/lipidJanus nanoparticlesin different organs 1 and 24 h after intravenous or inhalation administrations.Mean values for eight animals are presented.
Mentions: A Collison nebulizer connected tofour-port, nose-only exposure chambers was used for inhalation deliveryof drug-loaded nanoparticles. The measurement of nanoparticle sizeshowed that nebulization did not influence significantly on the sizeand stability of nanoparticles (Figure 2).The results presented on Figure 5 revealedthat 1 h after intravenous administration the distribution patternsof 155 nm (Figure 5a) and 450 nm (Figure 5b) Janus nanoparticles were similar to the preferentialparticle accumulation in mouse liver. However, slightly higher accumulationin the lungs was found for the larger nanoparticles. One hour afterinhalation delivery, nanoparticles of both sizes were detected inthe lungs (Figure 5c,d); however, the accumulationof nanoparticles with 450 nm in diameter was twice higher when comparedwith 155 nm nanoparticles. The analysis of the distribution profileof Janus nanoparticles 24 h after their intravenous administrationsshowed that the majority of nanoparticles of both sizes were foundin the liver and kidneys, while no fluorescent signal was detectedin lungs (Figure 5e,f). As was mentioned above,the accumulation of larger nanoparticles in the lungs 1 h after treatmentwas substantially higher when compared with smaller nanoparticles(Figure 5c,d). However, 24 h after inhalation,similarly to the intravenous administration, the 155 nm nanoparticleswere found only in the liver and kidneys (Figure 5g). In contrast, larger nanoparticles were still detectedin the lungs 24 h after inhalation and their content was comparablewith that after 1 h after treatment (Figure 5d, h). On the basis of these results we selected Janus nanoparticleswith the size of 450 nm for further inhalation treatment of mice withorthotopic lung cancer.

Bottom Line: Nanoparticles with dual load were used for their local inhalation delivery directly to the lungs of mice with orthotopic model of human lung cancer.In vivo experiments showed that the selected nanoparticles with two anticancer drugs with different mechanisms of action prevented progression of lung tumors.It should be stressed that anticancer effects of the combined treatment with two anticancer drugs loaded in the same nanoparticle significantly exceeded the effect of either drug loaded in similar nanoparticles alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey University , 160 Frelinghuysen Rd., Piscataway, New Jersey 08854, United States.

ABSTRACT
The aim of the present work is to synthesize, characterize, and test self-assembled anisotropic or Janus particles designed to load anticancer drugs for lung cancer treatment by inhalation. The particles were synthesized using binary mixtures of biodegradable and biocompatible materials. The particles did not demonstrate cyto- and genotoxic effects. Janus particles were internalized by cancer cells and accumulated both in the cytoplasm and nuclei. After inhalation delivery, nanoparticles accumulated preferentially in the lungs of mice and retained there for at least 24 h. Two drugs or other biologically active components with substantially different aqueous solubility can be simultaneously loaded in two-phases (polymer-lipid) of these nanoparticles. In the present proof-of-concept investigation, the particles were loaded with two anticancer drugs: doxorubicin and curcumin as model anticancer drugs with relatively high and low aqueous solubility, respectively. However, there are no obstacles for loading any hydrophobic or hydrophilic chemical agents. Nanoparticles with dual load were used for their local inhalation delivery directly to the lungs of mice with orthotopic model of human lung cancer. In vivo experiments showed that the selected nanoparticles with two anticancer drugs with different mechanisms of action prevented progression of lung tumors. It should be stressed that anticancer effects of the combined treatment with two anticancer drugs loaded in the same nanoparticle significantly exceeded the effect of either drug loaded in similar nanoparticles alone.

Show MeSH
Related in: MedlinePlus