Fibrous polypeptide based bioscaffold delivery of minocycline hydrochloride for nerve regeneration

Abstract

Neural tissue engineering is a technology with the potential to treat irreversible neurodegenerative diseases. We chose poly (γ-benzyl-l-glutamate) (PBG) and its hydrolyzed copolymer (poly (γ-benzyl-glutamate)80-r-(γ –glutamic acid)20) (PBGA) as the raw materials to make fibrous scaffolds by electrospinning process. These raw materials are biocompatible polypeptides which contain the neurotransmitter glutamate. Morphologically, the scaffolds consist of aligned fibers, which is important for directionality. Minocycline hydrochloride (MH) is a neuroprotective antibiotic obviously shown to enhance neurite growth, but is unstable in phosphate buffer solution. By incorporating and immobilizing MH into either PBG or PBGA polypeptide scaffolds, we created a stable drug delivery system. After 7-day release, the cumulative release of MH from PBGA scaffold was 42.65%. Nerve growth factor (NGF) responsive rat pheochromocytoma (PC12) cells were cultured on the scaffold to assess cell biocompatibility and proliferation. We found cell viability and differentiation improved when cultured on scaffolds bearing 2 wt% and 4 wt% of MH. PC12 cells cultured on PBGA incorporating 4 wt% MH exhibited the longest neurite outgrowth of 190.29 μm, the average is 33% increase over that of pristine PBGA after 5-days of NGF mediated differentiation. These polypeptide-based scaffolds loaded with MH are a promising drug delivery system for neural tissue engineering.