艾塞那肽温敏型凝胶纳米粒鼻喷剂研究

Exenatide Thermosensitive Gel Nanoparticle Nasal Spray

目的为改善艾塞那肽(exenatide,EX)注射液稳定性差、体内半衰期短和患者依从性差等缺点,本研究构建了EX温敏型凝胶纳米粒鼻腔给药系统。方法将聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒与泊洛沙姆(poloxamer)温敏凝胶相结合,以聚多巴胺(polydopamine,PDA)包被EX PLGA纳米粒,并制备温敏型凝胶(EX-NPS-GEL)。对其形态、载药量、相变温度、流变学、药物释放进行考察,并以2型糖尿病balb/c小鼠为模型,考察EX-NPS-GEL鼻腔给药后的降糖效果、血药浓度以及鼻粘膜刺激性。结果EX-NPS-GEL可长时间滞留在鼻黏膜处,有效延长动物体内降血糖时间,提高血药浓度。结论为EX治疗糖尿病提供了一种新的给药方式,提升了药物效果,缓解患者用药痛苦,为蛋白多肽类药物鼻腔递送的开发提供一定的启发和支持。

OBJECTIVE To construct a temperature sensitivegel nanoparticle nasal drug deliverysystem and improve the shortcomings of exenatide(EX)injection,such as poor stability,short half life in vivo,and poor patient compliance.METHODS Poly(lactic-co-glycolic acid)(PLGA)nanoparticles were combined with poloxamer temperature-sensitive gel,and EX was coated with polydopamine(PDA)peptide(PLGA)nanoparticles and prepared into temperature-sensitive gel(EX-NPS-GEL).The morphology,drug loading,phase transition temperature,rheology,and drug release of EX-NPS-GEL were investigated,and hypoglycemic test,blood drug concentration test and nasal mucosal irritation test were carried out in type 2 diabetes balb/c model mice.RESULTS EXNPS-GEL can be retained in the nasal mucosa for a long time,effectively prolonging the time of lowering blood sugar in the animal body and increasing the blood drug concentration.CONCLUSION It provides a new way of administration for the treatment of diabetes,improves the effect of drugs,relieves the pain of patients with medication,and provides certain inspiration and support for the development of protein peptide drugs for nasal delivery.