Dry eye syndrome (DES) is one of the most common disorders of the eye for which combined treatment includes modification of the ocular environment and pathogenic therapies. Cyclosporine A (CsA), a immunosuppressive agent, has been demonstrated to be effective for the treatment of DES but is limited clinically by its low ocular bioavailability due to poor water solubility. In this paper, methoxy poly (ethylene glycol)-poly (lactide) polymer (mPEG-PLA) micelles were investigated as alternative vehicles for the solubilization and delivery of CsA to the eye. The in vitro stability indicated that CsA-loaded micellar lyophilized powder was stable for at least 3 months and the release profile showed a sustained release manner of CsA from micelles physically. In vivo ocular distribution studies demonstrated that the micellar formulations exhibited a 4.5-fold increase in retention effect at eyes compared with 0.05% CsA emulsion. In addition, the in vivo pharmacokinetics profile showed that the CsA-loaded micelles could enhance the retention time, achieving longer effect toward the DES. These studies proposed an effective micelle formulation as a novel ocular drug delivery system to improve solubility and bioavailability of ophthalmic CsA-controlled delivery.

Metastatic cancers are prone to form metastasis at a distance and acquire drug resistance, which are very common clinically and major obstacles to successful chemotherapy. Besides the tumor itself, the lymphatic system is increasingly emerging as a new target for anticancer therapy because it is an important route of tumor metastasis. To specifically deliver drug to both highly metastatic tumor and its lymphatics, tumor- and tumor lymphatics-homing peptide (LyP-1) conjugated PEG-PCL micelles (LyP-1-PM) were first constructed. Artemisinin (ART), a natural product with potential anticancer and antilymphangiogenesis effects, was chosen as the model drug and associated into the micelles. Both PM and LyP-1-PM had similar physiochemical properties, about 30 nm in size with uniform distribution. Highly metastatic breast cancer MDA-MB-435S cells and lymphatic endothelial cells (LEC) were applied as cell models. Flow cytometry and confocal microscopy studies showed that LyP-1-PM exhibited its specificity to both cell lines evidenced by its higher cellular uptake than PM. LyP-1-PM-ART demonstrated higher inhibition effect than PM-ART against these two cell lines in cell apoptosis, cell cycle and cytotoxicity tests. Near-infrared imaging showed that LyP-1-PM was distributed more in orthotopic MDA-MB-435S tumor than PM. Further study by colocalization indicated that PM accumulated near blood vessels, while LyP-1-PM further homed to tumor lymphatic vessels. LyP-1-PM achieved higher antitumor efficacy than other ART formulations in vivo with low toxicity. Both in vitro and in vivo studies here proved that LyP-1 modification enhanced the specific delivery of ART or fluorescent probe loaded polymeric micelles to MDA-MB-435S and LEC. Therefore, LyP-1-PM might be promising in terms of specific delivery of therapeutic or imaging agents to both highly metastatic breast tumor and its lymphatics.

The past decades have witnessed enormous development of gold nanoparticles (AuNPs) and their applications in the biomedical field, an area in which they show infinite potential. Abundant investigations have been conducted in improving AuNP synthesis, aimed at obtaining water-dispersible ultrasmall AuNPs, which can exhibit biocompatibility, renal clearance and minimal toxicity. Due to their excellent x-ray attenuation ability, special optical properties and surface modification properties, AuNPs are reported to be promising as computed tomography contrast agents and can be applied in radiotherapy, photothermal and photodynamic therapies, and drug delivery. In this review, synthesis methods and toxicity of AuNPs have been summarized, emphasizing the preparation of ultra-small AuNPs. Applications of AuNPs in computed tomography imaging and cancer treatment are also considered, revealing their potential in the clinic.

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Introduction Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity. Methods The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37℃. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied. Results The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR. Conclusion The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.