Abstract：
There is a lack of effective therapeutic drugs for pulmonary arterial hypertension. Previous studies have demonstrated the positive cardiovascular system protective effects of the new peptide ACTY116. However, its stability in ordinary aqueous solution injections is poor and its half-life in the body is short, which has hindered the development of preparations. This study aimed to prepare in situ forming implants (ISFIs) of the peptide ACTY116 and investigate its impact on pulmonary arterial hypertension. We prepared ISFIs using NMP/TA as a solvent and PLGA as a polymer. These ISFIs exhibited low viscosity, low toxicity and sustained release properties. In a mouse model of pulmonary hypertension induced by SU5416/hypoxia, both ISFIs and ACTY116 peptides effectively reduced pulmonary hypertension, cardiac hypertrophy and pulmonary blood vessel wall thickness. In conclusion, this study highlights the potential of ACTY116 as a treatment for pulmonary arterial hypertension and suggests that incorporating it into an in-situ gel implant could be a promising option.
摘要：
缺乏有效的治疗肺动脉高压的药物。先前的研究已经证明了新肽ACTY116的积极心血管系统保护作用。然而,它在普通水溶液注射中的稳定性差，在体内的半衰期短，这阻碍了筹备工作的发展。本研究旨在制备肽ACTY116的原位形成植入物（ISFI），并研究其对肺动脉高压的影响。我们使用NMP/TA作为溶剂和PLGA作为聚合物制备ISFI。这些ISFI表现出低粘度，低毒性和持续释放特性。在SU5416/低氧诱导的小鼠肺动脉高压模型中，ISFI和ACTY116肽均有效降低肺动脉高压，心肌肥厚和肺血管壁厚度。总之,这项研究强调了ACTY116作为肺动脉高压治疗的潜力,并提示将其纳入原位凝胶植入物可能是一个有前景的选择.
