Amphiphilic N-(2,3-dihydroxypropyl)–chitosan–cholic acid micelles for paclitaxel delivery

Core cross-linked hyaluronan-styrylpyridinium micelles as a novel carrier for paclitaxel

Self-assembled nanoparticles of cholesterol-modifiedO-carboxymethyl chitosan (CCMC) were prepared to be used as a novel carrier for paclitaxel(PTX) in this study. CCMC-6.9 was synthesized by the covalent conjugation of cholesterol toO-carboxymethyl chitosan with the succinyl linkage and the degree of substitution (DS) ofthe cholesterol moiety was 6.9%. CCMC-6.9 formed self-assembled nanoparticles with a sizeof 209.5 nm in aqueous media. Paclitaxel-loaded CCMC-6.9 self-assembled nanoparticleswere prepared using a dialysis method and their characteristics were analyzed by dynamiclaser light scattering (LLS), transmission electron microscopy (TEM) and ultravioletspectroscopy (UV). PTX-loaded CCMC-6.9 self-assembled nanoparticles were almostspherical in shape and their size increased from 245.6 to 355.3 nm with PTX-loadingcontent increasing from 18.7% to 34.9%. In vitro release of PTX from CCMC-6.9self-assembled nanoparticles was carried out by the dynamic dialysis method. PTXcontinuously released in phosphate buffered saline (PBS) solutions for 84 h at37 °C and its release was sensitive to the pH of the release media. The biodistribution ofPTX-loaded CCMC-6.9 self-assembled nanoparticles was studied in female Balb/c mice.Compared with PTX in the solution of Cremophor EL (polyethoxylated castor oil)/ethanol(PTX-Cre), CCMC-6.9 self-assembled nanoparticles significantly increased theuptake of PTX in plasma, liver and spleen, but decreased the uptake in heart andkidney. These results suggest that CCMC-6.9 self-assembled nanoparticles caneffectively solubilize PTX and modify its tissue biodistribution, which may beadvantageous in enhancing the therapeutic index and reducing the toxicity of PTX.

The poor stability of micellar drug delivery system in vivo due to large volume dilution often leads to premature drug release with low therapeutic efficacy. In this study, shell cross-linked micelles of graftlike block copolymer bearing biodegradable e-caprolactone branches (PMAA-b-PFM) were prepared to be used as a novel carrier for paclitaxel (PTX). PTX was successfully encapsulated into the hydrophobic cores of the cross-linked micelles using the dialysis method. The resultant PTX-loaded cross-linked micelles were about 99 nm in diameter with spherical shape and high encapsulation efficiency. The PTX-loaded cross-linked micelles had smaller sizes and better stability as compared to the non-cross-linked controls. Fluorescence microscopy and flow cytometry studies showed that PTX-loaded cross-linked micelles had excellent cellular uptake ability by bone marrow derived macrophages and human glioma U87 cells. Cellular uptake of cross-linked micelles was found to be higher than non-cross-linked controls due to smaller size. In vitro cytotoxicity studies also revealed that the PTX-loaded cross-linked micelles exhibit high anti-cancer activity to U87 cells. These results suggested that cross-linked PMAA-b-PFM micelles could be a potential vehicle for delivering hydrophobic chemotherapeutic drugs to tumors.

Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel

Polymeric micelles of poly(2-ethyl-2-oxazoline)-block-poly(ε-caprolactone) copolymer as a carrier for paclitaxel

Hydrotropic hyaluronic acid conjugates: Synthesis, characterization, and implications as a carrier of paclitaxel

In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis (1H NMR), and contact angle evaluation. Micelles were produced by solvent evaporation method, and the critical micelle concentration was investigated by conductimetry. The obtained micelles were of 408-nm mean particle size, narrow size distribution (polydispersity index of 0.335) and presented positive surface charge around 30mV. The morphology of micelles assessed by transmission electron microscopy (TEM) revealed round and smooth surface, in agreement with dynamic light scattering measurements. The association efficiency determined by high-performance liquid chromatography (HPLC) was as high as 82%. The in vitro cytotoxicity of the unloaded and PTX-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cells, resulting in the absence of cell toxicity for all formulations. Moreover, the permeability of PTX-loaded micelles in Caco-2 monolayer and Caco-2/HT29-MTX co-culture model was determined. Results showed that the permeability of PTX was higher in Caco-2/HT29-MTX co-culture model compared with Caco-2 monolayer due to the mucoadhesive character of micelles, acting as a platform to deliver PTX at the sites of absorption. Therefore, it can be concluded that the PTX-loaded CS-g-PCL micelles, employed for the first time as PTX carriers, may be a potential drug carrier for the intestinal delivery of hydrophobic drugs, particularly anticancer agents.

We evaluated the efficacy of pH-sensitive micelles, formed by methoxy poly(ethylene glycol)-b-poly(β-amino ester) (PEG-PAE), as carriers for paclitaxel (PTX), a drug currently used to treat various cancers. PTX was successful encapsulated by a film hydration method. Micelles encapsulated more than 70% of the PTX and the size of the PTX-encapsulated micelles (PTX-PM) was less than 150 nm. In vitro experiments indicated that the micelles were unstable below pH 6.5. After encapsulation of PTX within the micelles, dynamic light scattering (DLS) studies indicated that low pH had a similar demicellization effect. An in vitro release study indicated that PTX was slowly released at pH 7.4 (normal body conditions) but rapidly released under weakly acidic conditions (pH 6.0). We demonstrated the safety of micelles from in vitro cytotoxicity tests on HeLa cells and the in vivo anti-tumor activity of PTX-PM in B16F10 tumor-bearing mice. We concluded that these pH-sensitive micelles have potential as carriers for anti-cancer drugs.

pH-responsive polymeric micelles based on poly(ethyleneglycol)-b-poly(2-(diisopropylamino) ethyl methacrylate) block copolymer for enhanced intracellular release of anticancer drugs

Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paclitaxel: Synthesis, characterization, and in vivo biodistribution

Novel alginate gel-core lipid nanocapsules (LNCs) consisting of hydrogel islets in an oil filled matrix and surrounded by a polymeric shell were prepared by hot homogenization and double emulsion method, for co-delivery of both hydrophilic (gemcitabine) and hydrophobic (paclitaxel) anticancer drugs. This system was prepared using a relatively simple and organic solvent-free method using only excipients that are approved by the FDA. The liquid oil matrix allowed the solubilization and encapsulation of hydrophobic drugs such as paclitaxel, whereas alginate hydrogel islets encapsulated hydrophilic drugs such as gemcitabine. Alginate gel-core LNCs were characterized with respect to particle size, polydispersity index (PDI), morphology, encapsulation efficiency, and in vitro release. Dual drug-loaded alginate gel-core LNCs had a particle size of 171.8 ± 4.1 nm and PDI of 0.201 ± 0.005, respectively, and showed core–shell type spherical morphology with a smooth surface. In addition, alginate gel core-LNCs underwent sustained release of both drugs. These results suggest that alginate gel core-LNCs may be used for co-delivery of hydrophilic (gemcitabine) and hydrophobic (paclitaxel) anticancer drugs.

Paclitaxel conjugated Fe3O4@LaF3:Ce3+,Tb3+ nanoparticles as bifunctional targeting carriers for Cancer theranostics application

Target delivering paclitaxel by ferritin heavy chain nanocages for glioma treatment

Hydrotropic magnetic micelles for combined magnetic resonance imaging and cancer therapy

Many tumor cells have acidic microenvironment that can be exploited for the design of pH-responsive drug delivery systems. In this work, well-defined pH-sensitive and biodegradable polymeric micelles were prepared and evaluate as carrier of paclitaxel (PTX). A diblock copolymer constituting of a poly(ethylene glycol) (PEG) and a polycaprolactone (PCL) segment linked by a pH-sensitive hydrazone bond (Hyd), which was denoted as mPEG-Hyd-PCL, was synthesized. The copolymer was assembled to micelles with mean diameters about 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles increased obviously in mildly acidic environments while kept unchanged in the neutral. No significant change in size was found on polymeric micelles without hydrazone (mPEG-PCL). PTX was loaded into micelles, and the anticancer drug released from mPEG-Hyd-PCL micelles was promoted by the increased acidity. In vitro cytotoxicity study showed that the PTX-loaded mPEG-Hyd-PCL micelles exhibited significantly enhanced cytotoxicity against HepG2 cells compared to the non-sensitive mPEG-PCL micelles. These results suggest that hydrazone-containing copolymer micelles with pH sensitivity and biodegradability show excellent potential as carriers of anticancer drugs.