Nanostructured Lipid Carriers Containing a High Percentage of a Pluronic Copolymer Increase the Biodistribution of Novel PDE4 Inhibitors for the Treatment of Traumatic Hemorrhage

BackgroundAmphiphilic 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.ResultsThe 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.ConclusionThis study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0103-7) contains supplementary material, which is available to authorized users.

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“…Free DiR exhibited an extensive distribution in RES [25]. Our in vivo bioimaging profiles confirmed this trend.…”

Section: Discussionsupporting

confidence: 74%

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

et al. 2015

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“…Amitriptyline release from the nanosystems was conducted using Franz diffusion cells, as in a previous study. 16 HPLC was used to quantify amitriptyline release into the receptor compartments of the Franz cells. …”

Section: Amitriptyline Release From the Nanosystemsmentioning

confidence: 99%

Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification

Chen¹,

Huang²,

Elzoghby³

et al. 2017

IJN

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The increasing death rate caused by drug overdose points to an urgent demand for the development of novel detoxification therapy. In an attempt to detoxify tricyclic antidepressant overdose, we prepared a lipid nanoemulsion, called squarticles, as the nanoantidote. Squalene was the major lipid matrix of the squarticles. Here, we present the animal study to investigate both the pharmacokinetic and pharmacodynamic effects of squarticles on amitriptyline intoxication. The anionic and cationic squarticles had average diameters of 97 and 122 nm, respectively. Through the entrapment study, squarticles could intercept 40%–50% of the amitriptyline during 2 h with low leakage after loading into the nanoparticles. The results of isothermal titration calorimetry demonstrated greater interaction of amitriptyline with the surface of anionic squarticles ( K a =28,700) than with cationic ones ( K a =5,010). Real-time imaging showed that intravenous administration of anionic squarticles resulted in a prolonged retention in the circulation. In a rat model of amitriptyline poisoning, anionic squarticles increased the plasma drug concentration by 2.5-fold. The drug uptake in the highly perfused organs was diminished after squarticle infusion, indicating the lipid sink effect of bringing the entrapped overdosed drug in the tissues back into circulation. In addition, the anionic nanosystems restored the mean arterial pressure to near normal after amitriptyline injection. The survival rate of overdosed amitriptyline increased from 25% to 75% by treatment with squarticles. Our results show that the adverse effects of amitriptyline intoxication could be mitigated by administering anionic squarticles. This lipid nanoemulsion is a potent antidote to extract amitriptyline and eliminate it.

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Nanomedicine for acute respiratory distress syndrome: The latest application, targeting strategy, and rational design

Qiao

Liu

Yang

et al. 2021

Acta Pharmaceutica Sinica B

110

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Nanostructured Lipid Carriers Containing a High Percentage of a Pluronic Copolymer Increase the Biodistribution of Novel PDE4 Inhibitors for the Treatment of Traumatic Hemorrhage

Cited by 7 publications

References 31 publications

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

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

Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification

Nanomedicine for acute respiratory distress syndrome: The latest application, targeting strategy, and rational design

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