Peptides that mimic the bioactivity of growth factors are rapidly emerging as therapeutics for a variety of drug delivery applications including therapeutic neovascularization. Neovascularization requires controlled and sustained delivery of proangiogenic factors to stimulate reperfusion of ischemic tissues. To this end, hydrogel nanoparticles were designed to provide sustained and tunable diffusion-based release of a pro-angiogenic peptide, QK. Inverse phase mini-emulsion polymerization (IPMP) was used to generate crosslinked poly(ethylene) glycol (PEG) hydrogel nanoparticles entrapped with the QK peptide. Peptide release kinetics were tuned through adjustments in nanoparticle crosslink density. This was achieved by altering the mole fraction of the crosslinking agent which allowed for the synthesis of low crosslink density (0.754 mmol cm⁻³) and high crosslink density (0.810 mmol cm⁻³) nanoparticles. Nanoparticle tracking analysis revealed narrow particle size distributions and similar particle sizes regardless of crosslink density (225 ± 75 nm and 233 ± 73 nm, for low and high crosslink density nanoparticles, respectively). The zeta potential was found to be −26 mV for blank nanoparticles and +4 mV in the case of QK-loaded nanoparticles. The resulting nanoparticle crosslink density impacted both peptide loading as well as release kinetics. In terms of cumulative fractional release and weight of peptide released per mass of nanoparticle, higher crosslink density nanoparticles resulted in slower peptide release kinetics. The IPMP process preserved the QK secondary structure and its bioactivity as confirmed using circular dichroism spectroscopy and a Matrigel tubulogenesis assay, respectively, with released peptide. The presented nanoparticles hold great potential for use as drug delivery carriers for stimulation of therapeutic neovascularization of ischemic tissues.

中文翻译：

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具有可调节网络特性的水凝胶纳米颗粒的设计和表征，可持续释放VEGF模拟肽

模仿生长因子生物活性的肽作为各种药物递送应用（包括治疗性新血管形成）的治疗剂正在迅速出现。新血管形成需要控制和持续递送促血管生成因子，以刺激缺血组织的再灌注。为此，水凝胶纳米颗粒被设计为提供持续的和可调节的基于扩散的促血管生成肽QK的释放。反相微乳液聚合（IPMP）用于生成被QK肽包裹的交联聚（乙二醇）（PEG）水凝胶纳米颗粒。通过调节纳米粒子交联密度来调节肽释放动力学。通过改变交联剂的摩尔分数可以实现低交联密度（0.754 mmol·cm）的合成。^-3）和高交联密度（0.810 mmol cm ^-3）纳米粒子。纳米颗粒跟踪分析显示，无论交联密度如何（窄交联密度纳米颗粒和高交联密度纳米颗粒分别为225±75 nm和233±73 nm），粒度分布窄且粒径相似。发现空白纳米颗粒的ζ电位为-26 mV，而装有QK的纳米颗粒的ζ电位为+4 mV。所得的纳米颗粒交联密度影响肽负载以及释放动力学。就累积分数释放和每质量纳米颗粒释放的肽的重量而言，较高的交联密度纳米颗粒导致较慢的肽释放动力学。IPMP流程保留了QK二级结构及其生物活性，分别使用圆二色光谱法和Matrigel肾小管生成测定法对释放的肽进行了确认。