Micelle-solubilized axitinib for ocular administration in anti-neovascularization.

The development of new blood vessels is directly related to the occurrence of eye diseases. Anti-angiogenic drugs can theoretically be extended to the treatment of ophthalmic diseases. In this study, axitinib, a class of tyrosine kinase inhibitors, was loaded via the amphiphilic copolymer MPEG-PCL, improving its dispersibility in water. Axitinib-loaded micelles showed low toxicity in concentration gradient assays. Additionally, multiple doses by scratch assay confirmed that axitinib had no significant effect on normal cell migration, and biosafety test results showed good cell compatibility. After we established the corneal neovascularization model after an alkali burn in rats, the anti-angiogenic efficacy was tested, with dexamethasone as a positive control. The results showed that axitinib-loaded micelles had anti-angiogenic effects without obvious tissue toxicity. As a class of targeted tyrosine kinase inhibitors, axitinib can be used in the treatment of ocular neovascular diseases through nanocrystallization.

Engineered Non-Viral Gene Vectors for Combination Cancer Therapy: A Review.

Following the US Food and Drug Administration's approval of gene therapy drugs, the great potential of disease gene therapy is once again being taken seriously. However, finding a safe and efficient gene delivery vector remains the biggest challenge to successful gene therapy. To overcome this, engineered non-viral gene delivery vectors are continually being developed, despite their lower efficiencies compared with viral vectors. However, the complex biological barriers and instability caused by charge interactions mean that, no major breakthroughs have been made in the clinical development of these non-viral gene vectors. Nevertheless, the functions of the engineered polymer gene carriers are continuously expanding, and success has been achieved with the combined use of therapeutic molecules and targeted delivery. These polymer gene-carrier vectors offer a broader choice of new treatments for diseases ever before.

Combination of dexamethasone and Avastin® by supramolecular hydrogel attenuates the inflammatory corneal neovascularization in rat alkali burn model.

Corneal neovascularization (CNV) is one of the leading causes of vision loss and a high-risk factor for transplant rejection. The present study proposed a supramolecular hydrogel comprised of MPEG-PCL micelles and α-cyclodextrin (α-CD) for co-delivery of dexamethasone sodium phosphate (Dexp) and Avastin® (Ava), and further evaluated its therapeutic efficacy in rat alkali burn model. A physical mixing of Dexp/Ava, MPEG-PCL micelles, and α-CD aqueous solution leads to a spontaneous formation of the supramolecular hydrogel via a "host-guest" recognition between MPEG and α-CD. The supramolecular hydrogel provides a relatively quick release of Dexp over Ava during the study of the 5-day in vitro release. The results of in vitro cytotoxicity test and wound healing assay illustrated that the proposed supramolecular hydrogel was non-toxic against L-929 and HCEC cells and did not significantly affect the migration of HCEC cells after 24h incubation. The corneal distribution test suggested that the precorneal duration of Ava was significantly extended by the supramolecular hydrogel with respect to its solution formulation. Moreover, the supramolecular hydrogel showed high ocular biocompatibility and was a non-irritant after topical instillation. Furthermore, the Dexp-Ava hydrogel medication, but not by Ava solution and Ava hydrogel medication, could greatly attenuate the alkali burn-induced corneal inflammation and remarkably suppress the corneal neovascularization via the downregulation of VEGF, CD31, and α-SMA expression in the rat alkali burn model. As a result, the combined Dexp and Ava by supramolecular hydrogel exhibited an advantage over Ava monotherapy approach, which might be a promising alternative therapy for inflammatory CNV.

Star-Shaped Amphiphilic Hyperbranched Polyglycerol Conjugated with Dendritic Poly(l-lysine) for the Codelivery of Docetaxel and MMP-9 siRNA in Cancer Therapy.

The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.