负载CD133靶向纳米脂质体的聚乳酸-聚羟基乙酸微球的双重缓释普萘洛尔靶向治疗血管瘤作用和机制研究

Propranolol is the first-line drug for the treatment of hemangiomas, however, its side effects and overdosage limit its clinical application. The sustained-release delivery system of lipid polylactic acid-polyglycolic acid (PLGA) microspheres constructed in our previous study succeeded in the sustained release of propranolol and better inhibited the growth of hemangiomas than propranolol. CD133-positive hemangiomas stem cells are the source of development of hemangiomas. Our previous studies found that targeted hemangio-hematopoietic stem cells can better inhibit the proliferation of hemangiomas. In this study, we propose that CD133-targeting propranolol liposomes are loaded into PLGA microspheres to construct dual-release-targeted lipid microspheres. Due to the dual sustained release of propranolol from liposomes and microspheres, the dual release-targeted lipid microspheres are expected to reduce the dosage and side effects of propranolol. After release from microspheres, the CD133-targeting nanoliposomes can target and kill CD133-positive hemangiomas stem cells. This study, for the first time, utilizes double-release microspheres and molecular targeting strategies to achieve sustained release of propranolol and target hemangio-lineage stem cells, providing new ideas for the treatment of hemangiomas. This study can provide a new type of anti-angiogenic slow-release targeting microspheres with high efficiency and low toxicity, which has important theoretical significance and potential clinical value for the treatment of hemangiomas.

普萘洛尔是治疗血管瘤的一线药物，然而其毒副作用和服药次数过频限制了其临床应用。我们前期构建的脂质聚乳酸-聚羟基乙酸（PLGA）微球的缓释给药系统成功的实现普萘洛尔的缓释，较普萘洛尔更好的抑制血管瘤生长。CD133阳性血管瘤干细胞是血管瘤发生发展的根源，我们前期研究发现靶向杀伤血管瘤干细胞可以更好的抑制血管瘤增殖。在本研究中，我们拟将CD133靶向普萘洛尔脂质体负载于PLGA微球中构建为双重缓释靶向脂质微球。由于脂质体和微球对普萘洛尔的双重缓释作用，该双重缓释靶向脂质微球预期可大大减少普萘洛尔的服药次数和毒副作用，而且CD133靶向脂质体从微球释出后能靶向杀伤血管瘤干细胞。该研究首次利用双重缓释微球和分子靶向的新策略实现普萘洛尔缓释和靶向血管瘤干细胞，为血管瘤治疗提供新思路。该研究可提供一种高效低毒的新型抗血管瘤缓释靶向微球，对血管瘤治疗具有重要理论意义和潜在临床应用价值。

该课题的研究目标为明确负载CD133靶向纳米脂质体的聚乳酸-聚羟基乙酸微球的双重缓释普萘洛尔靶向治疗血管瘤的作用和机制。从纳米药物这个新视点来实现药物缓释和精准的靶向治疗，为血管瘤的治疗提供新思路和新策略。.该课题按照原计划进行，成功构建聚乳酸-聚羟基乙酸微球缓释给药系统后，将CD133靶向普萘洛尔脂质体负载于聚乳酸-聚羟基乙酸微球中构建为双重缓释靶向脂质微球，该双重缓释靶向脂质微球大大减少了普萘洛尔的服药次数和毒副作用，而且CD133靶向脂质体从微球释出后能靶向杀伤血管瘤干细胞。能够有效降低口服普萘洛尔治疗血管瘤时的毒副作用和服药次数。