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Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone).

Lee RS, Lin CH, Aljuffali IA, Hu KY, Fang JY - J Nanobiotechnology (2015)

Bottom Line: In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution.Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles.This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

View Article: PubMed Central - PubMed

Affiliation: The Center of General Education, Chang Gung University, Kweishan, Taoyuan, Taiwan. shen21@mail.cgu.edu.tw.

ABSTRACT

Background: Amphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery.

Results: The critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146-199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles.

Conclusion: This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

No MeSH data available.


The LDH release of neutrophils (a) and the cell viability (%) of 293T cells (b) and HaCaT cells (c) treated by PNiPAAm8-b-PCL20 micelles. Each value represents the mean ± SD (n = 3).
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Fig6: The LDH release of neutrophils (a) and the cell viability (%) of 293T cells (b) and HaCaT cells (c) treated by PNiPAAm8-b-PCL20 micelles. Each value represents the mean ± SD (n = 3).

Mentions: The preliminary examination on the cytotoxicity of PNiPAAm8-b-PCL20 was performed in various cells. Figure 6 shows the results. Neutrophils are the main leukocytes (50–70%) in systemic circulation. The cytotoxicity of neutrophils can be associated with disruption of membrane integrity as indicated by LDH. As demonstrated in Figure 6a, micelle intervention does not show cytotoxicity against human neutrophils at all concentrations tested (1.5–48 μg/ml). Human embryonic kidney cells (293T) and keratinocytes (HaCaT) were chosen as the model systems to evaluate the cytotoxicity of micelles. Figure 6b, c exhibit the cell viability (%) of 293T and HaCaT in the presence of micelles, respectively. The copolymer micelles did not elicit a significant cytotoxicity to both cell lines compared to the nontreatment control.Figure 6


Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone).

Lee RS, Lin CH, Aljuffali IA, Hu KY, Fang JY - J Nanobiotechnology (2015)

The LDH release of neutrophils (a) and the cell viability (%) of 293T cells (b) and HaCaT cells (c) treated by PNiPAAm8-b-PCL20 micelles. Each value represents the mean ± SD (n = 3).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4472254&req=5

Fig6: The LDH release of neutrophils (a) and the cell viability (%) of 293T cells (b) and HaCaT cells (c) treated by PNiPAAm8-b-PCL20 micelles. Each value represents the mean ± SD (n = 3).
Mentions: The preliminary examination on the cytotoxicity of PNiPAAm8-b-PCL20 was performed in various cells. Figure 6 shows the results. Neutrophils are the main leukocytes (50–70%) in systemic circulation. The cytotoxicity of neutrophils can be associated with disruption of membrane integrity as indicated by LDH. As demonstrated in Figure 6a, micelle intervention does not show cytotoxicity against human neutrophils at all concentrations tested (1.5–48 μg/ml). Human embryonic kidney cells (293T) and keratinocytes (HaCaT) were chosen as the model systems to evaluate the cytotoxicity of micelles. Figure 6b, c exhibit the cell viability (%) of 293T and HaCaT in the presence of micelles, respectively. The copolymer micelles did not elicit a significant cytotoxicity to both cell lines compared to the nontreatment control.Figure 6

Bottom Line: In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution.Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles.This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

View Article: PubMed Central - PubMed

Affiliation: The Center of General Education, Chang Gung University, Kweishan, Taoyuan, Taiwan. shen21@mail.cgu.edu.tw.

ABSTRACT

Background: Amphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery.

Results: The critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146-199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles.

Conclusion: This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

No MeSH data available.