Herceptin-functionalized pure paclitaxel nanocrystals for enhanced delivery to HER2-postive breast cancer cells.

The objective of this study was to prepare Herceptin (HCT)-functionalized paclitaxel nanocrystals and evaluated their cell-specific interactions, cellular accumulation, and growth inhibition in HER2-positve breast cancer cells as a tumor-targeted delivery module. Paclitaxel (PTX) was fabricated in the form of nanocrystals (PNCs) by a sono-precipitation method, and HCT were coated using a facile non-covalent method (PNCs-HCT). Our results showed that the PNCs-HCT were stable for at least 1month at 4°C with no noticeable desorption of HCT. The release test showed that PNCs-HCT exhibited sustained drug release similar to only PNCs but with a higher release rate than only PTX powder. Cellular uptake, cytotoxicity, and cell cycle arrest studies revealed that PNCs-HCT exhibit greater binding affinity and higher cell-specific internalization to HER2-positive breast cancer cell lines as compared to PNCs, followed by enhanced cell growth inhibition. HCT-functionalized PNCs presented in this study offer a promising strategy for targeted pure drug nanocrystal delivery and enhancing the efficiency of anticancer therapy.

Nitric oxide-releasing chitosan film for enhanced antibacterial and in vivo wound-healing efficacy.

Nitric oxide (NO) is a promising therapeutic agent with antibacterial and wound-healing properties. However, the gaseous state and short half-life of NO necessitate a formulation that can control its storage and release. In this study, we developed NO-releasing films (CS/NO film) composed of chitosan (CS) and S-nitrosoglutathione (GSNO) as a NO donor. Thermal analysis demonstrated molecular dispersion of GSNO in the films. In vitro release study revealed that NO release from CS/NO films followed Korsmeyer-Peppas model with Fickian diffusion kinetics. Moreover, the CS/NO film showed a stronger antibacterial activity against Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) than the CS film. Further, the CS/NO film accelerated wound healing and epithelialization in a rat model of full-thickness wounds as compared to the CS film. Histopathological studies revealed that CS/NO films favorably enhanced the re-epithelialization and reconstruction of wounded skin. Therefore, our results suggest that CS/NO films could be a suitable formulation for treating full-thickness wounds.

Size-controlled biodegradable nanoparticles: preparation and size-dependent cellular uptake and tumor cell growth inhibition.

Biodegradable nanoparticles with diameters below 1000nm are of great interest in the contexts of targeted delivery and imaging. In this study, we prepared PLGA nanoparticles with well-defined sizes of ∼70nm (NP70), ∼100nm (NP100), ∼200nm (NP200), ∼400nm (NP400), ∼600nm (NP600) and ∼1000nm (NP1000) using facile fabrication methods based on a nanoprecipitation and solvent evaporation techniques. The nanoparticles showed a narrow size distribution with high yield. Then the size-controlled biodegradable nanoparticles were used to investigate how particle size at nanoscale affects interactions with tumor cells and macrophages. Interestingly, an opposite size-dependent interaction was observed in the two cells. As particle size gets smaller, cellular uptake increased in tumor cells and decreased in macrophages. We also found that paclitaxel (PTX)-loaded nanoparticles showed a size-dependent inhibition of tumor cell growth and the size-dependency was influenced by cellular uptake and PTX release. The size-controlled biodegradable nanoparticles described in this study would provide a useful means to further elucidate roles of particle size on various biomedical applications.