Dual Delivery of NGF and bFGF Coacervater Ameliorates Diabetic Peripheral Neuropathy via Inhibiting Schwann Cells Apoptosis

Diabetic neuropathy is a kind of insidious complications that impairs neural and vascular function and ultimately leads to somatic and visceral denervation. Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are important neurotrophic factors for stimulating angiogenesis and improving peripheral nerve function. Administrating a single factor has good therapeutic effect on diabetic peripheral neuropathy (DPN). However, the short half-life and rapid diffusion of growth factors under physiological conditions limits its clinical applications. Here, we used a biodegradable coacervate, composed of heparin and polycation, to dominate the combined release of bFGF and NGF in a steady fashion. We found this combined growth factors (GFs) coacervate, administered as a single injection, improved motor and sensory functions, restored morphometric structure and decreased apoptosis of Schwann cells in a rat model of prolonged DPN. Similarly the GFs coacervate, as compared with free bFGF and NGF combination, markedly reduced the apoptosis level of a rat Schwann cell line, RSC 96 cells in vitro. We also demonstrated that neuroprotective effects of the GFs coacervate in both rat DPN model and hyperglycemia-induced RSC 96 cell model is likely due to suppression of endocytoplasmic reticulum stress (ERS).