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

Abstract

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.

Temperature-Responsive Smart Nanocarriers for Delivery Of Therapeutic Agents: Applications and Recent Advances

“…167,170,174,177–180 For instance, by means of FTIR spectra and calculation of Gibbs free energies for the hydrogen-bonded intermolecular complexes, the importance of hydrogen bonds in creating the NPs is realized. 181 In addition, cross-linked and non-cross-linked states of the polymers can be studied by FTIR. 182 …”

“…Also, the early stages of NPs creation and closer insight into the particles interior are realized via SAXS and SANS. 181 …”

Temperature-Responsive Multilayer Films of Micelle-Based Composites for Controlled Release of a Third-Generation EGFR Inhibitor

“…Endowing PEMs with enhanced functionality through the use of block copolymer micelles (BCMs) as film constituents is attractive due to their high loading capacity of active agents and responsiveness to various environmental stimuli. In recent years, advances in block copolymer fabricating techniques, especially the developments of controlled radical polymerization techniques allowing the synthesis of a variety of block copolymers, have facilitated in the development of functional BCM-incorporated LBL films. , In aqueous solution, nanoscale micelles with hydrophilic coronae and hydrophobic cores form by block copolymers via self-assembly, which could further absorb/release hydrophobic materials such as drugs, proteins, dyes, or genes . Fabrication of multilayer films using BCMs as building blocks is particularly attractive due to their large surface/volume ratio, defined structure, and high loading capacity of active agents. , …”

A Review of Polymeric Micelles and Their Applications

“…Dioctadecyl-3,3,3 ,3 -tetramethylinotricarbocyanine iodide (DiR) was used as a control for imaging rat organs. DiR-loaded micelles of PNIPAM-b-PCL showed improved signals in the lungs, kidney, stomach, and intestine compared with DiR solution (Figure 9) [106]. Inverse micelles prepared using the water/oil microemulsion method were compared with inverse micelles formed via simulation studies [81].…”