Induction of Angiogenesis by Controlled Delivery of Vascular Endothelial Growth Factor Using Nanoparticles

Authors


Correspondence

C. Gu, M.D., Ph.D. and D. Yi, M.D., Ph.D., Changle Road 15#, 710032, Xi'an, China.

Tel.: +86-29-84775311 and +86-29-84775307;

Fax: +86-29-83210092 and +86-29-83210092;

E-mails: guchunhu@163.com and yidh.fmmu@yahoo.com.cn

Summary

Aims

The study reports the feasibility and efficiency of vascular endothelial growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl methacrylated dextran (Dex-GMA) and gelatin for therapeutic angiogenesis.

Methods

The nanoparticles were prepared using phase separation method, and the drug release profile was determined by ELISA study. The bioactivity of VEGF-incorporated nanoparticles (VEGF-NPs) were determined using tube formation assay. A rabbit hind limb ischemia model was employed to evaluate the in vivo therapeutic effect. Blood perfusion was measured by single-photon emission computed tomography (SPECT). Vessel formation was evaluated by contrast angiography and immunohistochemistry.

Results

The nanoparticles synthesized were spherical in shape with evenly distributed size of about 130 ± 3.5 nm. The VEGF encapsulated was released in a biphase manner, with the majority of 69% released over 1–12 days. Tube formation assays showed increased tubular structures by VEGF-NP compared with empty nanoparticles and no treatment. Both free VEGF and VEGF-NP significantly increased blood perfusion compared with empty nanoparticles (both < 0.001), but it was much higher in VEGF-NP-treated limbs (< 0.001). Contrast angiography and immunohistological analysis also revealed more significant collateral artery formation and higher capillary density in VEGF-NP-treated limbs.

Conclusions

Dex-GMA and gelatin-based nanoparticles could provide sustained release of VEGF and may serve as a new way for angiogenesis.

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