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These results suggest that HER2-mediated endocytosis is involved in the PILs formulation. The ability of the PILs formulation to efficiently and specifically deliver paclitaxel to the HER2-overexpressing cancer cells implies that it is a promising strategy for tumor-specific therapy for HER2-overexpressing breast cancers.

To obtain an active-targeting carrier to cancer cells, folate-conjugated stearic acid grafted chitosan oligosaccharide (Fa-CSOSA) was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The substitution degree is 22.1%. The critical micelle concentrations (CMCs) of Fa-CSOSA were 0.017 and 0.0074 mg ml(-1) in distilled water and PBS (pH 7.4), respectively. The average volume size range of Fa-CSOSA micelles was 60-120 nm. The targeting ability of Fa-CSOSA micelles was investigated against two kinds of cell lines (A549 and Hela), which have different amounts of folate receptors in their surface. The results indicated that Fa-CSOSA micelles presented a targeting ability to the cells (Hela) with a higher expression of folate receptor during a short-time incubation (<6 h). As incubation proceeded, the special spatial structure of the micelles gradually plays a main role in cellular internalization of the micelles. Good internalization of the micelles into both Hela and A549 cells was shown. Then, paclitaxel (PTX) was encapsulated into the micelles, and the content of PTX in the micelles was about 4.8% (w/w). The average volume size range of PTX-loaded micelles was 150-340 nm. Furthermore, the anti-tumor efficacy in vitro was investigated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method. The IC(50) of Taxol (a clinical formulation containing PTX) on A549 and Hela cells was 7.0 and 11.0 µg ml(-1), respectively. The cytotoxicity of PTX-loaded micelles was improved sharply (IC(50) on A549: 0.32 µg ml(-1); IC(50) on Hela: 0.268 µg ml(-1)). This is attributed to the increased intracellular delivery of the drug. The Fa-CSOSA micelles that are presented may be a promising active-targeting carrier candidate via folate mediation.

Solid dispersions (SD) of nitrendipine (NTD), a poorly water-soluble drug, were prepared using the meltmixing method with hydrophilic silica particles (Aerosil and Sylysia) with different particle size and specific surface areas as carriers. Powder X-ray diffraction and differential scanning calorimetry evaluation showed that NTD in the SDs treated with the melt-mixing method was dispersed in the amorphous state. FT-IR spectroscopy obtained with the SDs indicated the presence of hydrogen bonding between the secondary amine groups of NTD and silanol groups of silica particles. The dissolution property of NTD in the SDs was remarkably improved regardless of the grade of silica. At the end of the dissolution test (60 min) the concentrations of NTD for the SDs with Aerosil 200 and Sylysia 350 were 8.88 and 10.09 m mg/ml, corresponding to 28 and 31 times that of the original NTD crystals, respectively. The specific surface area and the adsorbed water amount of the SDs were also significantly improved. The rapid dissolution rate from the SDs was attributed to the amorphization of drug, improved specific surface area and wettability than the original drug crystals. In the stability test, powder X-ray diffraction pattern indicated that amorphous NTD in the SD with Aerosil 200 was stable for at least 1 month under the humid conditions (40°C/75% RH).