Thermosensitive Micelles Research Articles

The antitumor effect of novel docetaxel-loaded thermosensitive micelles

To further evaluate the novel docetaxel-loaded micelle based on the biodegradable thermosensitive copolymer poly( N-isopropylacrylamide-co-acrylamide)- b-poly( dl-lactide) that we had synthesized before, in this paper, we studied its in vitro cytotoxicity in three different tumor cell lines by standard MTT assays using different tumor cell lines, followed by studies of acute toxicity and the tumor distribution studies which were conducted in Kunming mice. Meanwhile, the in vivo antitumor efficacy as well as toxicity of the micelle was evaluated in C57BL/6 mice. According to our findings, the in vitro cytotoxicity of docetaxel-loaded micelles was lower than that of the conventional docetaxel formulation at 37 °C, while hyperthermia greatly enhanced the efficacy of drug-loaded micelles. The acute toxicity study showed reduced toxicity of docetaxel-loaded micelle compared to that of conventional docetaxel formulation. Moreover, docetaxel-loaded micelle enabled a prominent higher docetaxel concentration in tumor than conventional docetaxel formulation. Furthermore, a significantly higher antitumor efficacy was observed in mice treated with docetaxel-loaded micelles accompanied by hyperthermia; docetaxel-loaded micelles also caused less body weight loss of mice. This study demonstrates an increased antitumor efficacy and reduced toxicity of the novel docetaxel-loaded micelle and indicates its prospect of clinical applications.

Hydrolysable core-crosslinked thermosensitive polymeric micelles: Synthesis, characterisation and in vivo studies

In this study, core-crosslinked (CCL) biodegradable thermosensitive micelles based on mPEG 5000 and N-(2-hydroxyethyl)methacrylamide)-oligolactates (mPEG -b-p(HEMAm-Lac n )) were synthesised and their properties investigated. Rapidly heating aqueous solutions of partially methacrylated block copolymers to above their critical micelle temperature (CMT), followed by illumination in presence of a photoinitiator yielded almost monodisperse CCL micelles with a size of 68±7 nm. Either below the CMT or after addition of sodium dodecyl sulphate, the non-crosslinked (NCL) micelles rapidly disintegrated whereas the CCL micelles kept their integrity. NCL micelles fell apart after 5 h in pH 7.4 at 37 °C as a result of the hydrolysis of lactate side chains, whereas the CCL micelles had a much higher stability and only degraded after cleavage of the ester bonds in the crosslinks. The circulation kinetics and biodistribution of CCL micelles were considerably better than those of NCL micelles, i.e., 58% of the injected dose (ID) of CCL versus 6% of NCL micelles was recovered in the circulation 4 h post-injection. Furthermore, the liver uptake of the CCL micelles (10% ID) was much lower than that of the NCL micelles (24% ID) 4 h after administration, while tumour accumulation was almost 6 times higher for the CCL micelles. Likely, NCL micelles dissociated after i.v. administration and/or were opsonised and captured by macrophages while the dense PEG shell of CCL micelles made them less prone towards opsonisation. The excellent physical stability of these degradable CCL micelles and very favourable biodistribution profile renders them very suitable for drug targeting purposes.

Self-assembled, thermosensitive micelles of a star block copolymer based on PMMA and PNIPAAm for controlled drug delivery

A four-arm star block copolymer, comprised of a hydrophobic PMMA arm and an average of three hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) arms were designed and synthesized from the molecular level. The amphiphilic star block copolymer is capable of self-assembling into micelles in water, which was confirmed by FT-IR, (1)H NMR and fluorescence spectroscopy. Transmission electron microscopy images showed that these nanoparticles were regularly spherical in shape. The micelles showed reversible dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST) for PNIPAAm at around 34 degrees C, observed by optical absorbance measurements. Resulted polymeric micelles loaded with prednisone acetate showed a much improved drug release behavior due to the special micellar structure.

Conformational Transition of Tethered Poly(N-isopropylacrylamide) Chains in Coronas of Micelles and Vesicles

Thermosensitive micelles and vesicles in water were prepared using narrowly distributed polystyrene-b-poly(N-isopropylacrylamide) (PS-b-PNIPAM) diblock copolymers, and the conformational changes of PNIPAM blocks in the coronas of micelles and vesicles were investigated by a combination of static and dynamic laser light scattering. Our results reveal that PNIPAM chains forming brushes in the corona of the micelles undergo a continuous collapse transition, which is consistent with the theoretical predictions. PNIPAM brushes in the coronas of the vesicles exhibit a broad transition from 28 to 36 °C with a shrinking in the range 20−28 °C. The shrinking at a low temperature is attributed to the interchain overlapping of the dense brushes on the concave surface of the vesicle. On the other hand, the vesicles become hollow with temperature increasing because of the collapse of the PNIPAM chains in the inside corona of the vesicle.

温度応答型ミセルを形成するジブロックコポリマーのリビングカチオン重合による合成

温度応答型ミセルを形成するジブロックコポリマーのリビングカチオン重合による合成

Thermosensitive Micelles Self‐Assembled by Novel N‐Isopropylacrylamide Oligomer Grafted Polyphosphazene

AbstractSummary: A novel thermosensitive amphiphilic copolymer of PNIPAm grafted polyphosphazene (PNIPAm‐g‐PPP) has been synthesized through a co‐substitution reaction of poly(dichlorophosphazene) with amino terminated NIPAm oligomer and glycine ethyl ester (GlyEt). The polymer obtained had a molar ratio of 1:5.25 PNIPAm to GlyEt and had a lower critical solution temperature (LCST) near 30 °C. The formation of polymeric micelles was confirmed by fluorescence, dynamic light scattering and transmission electron microscopy measurements.The structure and formation of thermosensitive micelles of poly(N‐isopropylacrylamide) grafted polyphosphazenes synthesized here.imageThe structure and formation of thermosensitive micelles of poly(N‐isopropylacrylamide) grafted polyphosphazenes synthesized here.

Thermo-sensitive self-assembled micelles prepared by cholic acid and poly(N-isopropylacrylamide).

Thermo-sensitive self-assembled micelles prepared by cholic acid and poly(N-isopropylacrylamide).

Thermosensitive Micelle-Forming Block Copolymers of Poly(ethylene glycol) and Poly(N-isopropylacrylamide)

Thermosensitive Micelle-Forming Block Copolymers of Poly(ethylene glycol) and Poly(<i>N</i>-isopropylacrylamide)