Treatment of Experimental Arthritis with Stealth-Type Polymeric Nanoparticles Encapsulating Betamethasone Phosphate
Treatment of Experimental Arthritis with Stealth-Type Polymeric Nanoparticles Encapsulating Betamethasone Phosphate
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DOI：
10.1124/jpet.108.150276
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发表时间：
2009-05-01
影响因子：
3.5
通讯作者：
Higaki, Megumu
中科院分区：
文献类型：
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作者：
Ishihara, Tsutomu;Kubota, Tetsushi;Higaki, Megumu
我们研究了包封在聚（D，L-乳酸/乙醇酸）（PLGA）/聚（D，L-乳酸）（PLA）均聚物和聚乙二醇（PEG）-嵌段-PLGA/PLA共聚物（隐形纳米类固醇）的生物相容性和生物可降解混合纳米颗粒中的21-磷酸倍他米松二钠（BP）在实验性关节炎模型中的治疗活性。制备了大小为45至115 nm的各种隐形纳米类固醇，然后静脉内给药给患有佐剂性关节炎（AA）的大鼠和患有抗II型胶原抗体诱导的关节炎（阿比亚）的小鼠。使用体内成像系统确定隐形纳米颗粒与Cy 7在发炎关节中的积累。A型隐形纳米甾体由PLA（2.6 kDa）和PEG（5 kDa）-PLA（3 kDa）组成，PEG含量为10%，直径为115 nm，具有最高的抗炎活性。在AA大鼠中，单次注射A型隐形纳米类固醇（40 μ g BP）在1天内获得了35%的爪炎症减少，并维持了9天，而相同剂量的非隐形纳米类固醇和3倍高的游离BP显示出明显较弱的反应。在阿比亚小鼠中，单次注射A型隐形纳米类固醇（3 μ g BP）导致1周后炎症反应完全缓解。此外，在AbAI小鼠中，A型隐形纳米颗粒在发炎关节中的积累与炎症的严重程度平行。在实验性关节炎中使用A型隐形纳米类固醇获得的观察到的强大治疗益处可能是由于延长的血液循环和靶向发炎关节以及其原位持续释放。
We examined the therapeutic activity of betamethasone disodium 21-phosphate (BP) encapsulated in biocompatible and biodegradable blended nanoparticles of poly (D,L-lactic/glycolic acid) (PLGA)/poly(D,L-lactic acid) (PLA) homopolymers and polyethylene glycol (PEG)-block-PLGA/PLA copolymers (stealth nanosteroid) in experimental arthritis models. Various stealth nanosteroids with a size of 45 to 115 nm were prepared and then intravenously administered to rats with adjuvant arthritis (AA) rats and mice with anti-type II collagen antibody-induced arthritis (AbIA). The accumulation of stealth nanoparticles with Cy7 in inflamed joints was determined using an in vivo imaging system. The type A stealth nanosteroid, composed of PLA (2.6 kDa) and PEG (5 kDa)-PLA (3 kDa), with a PEG content of 10% and a diameter of 115 nm, exhibited the highest anti-inflammatory activity. In AA rats, a 35% decrease in paw inflammation was obtained in 1 day and maintained for 9 days with a single injection of the type A stealth nanosteroid (40 mu g of BP), whereas the same does of nonstealth nanosteroid and 3 times higher free BP showed a significantly weaker response. In AbIA mice, a single injection of the type A stealth nanosteroid (3 mu g of BP) resulted in complete remission of the inflammatory response after 1 week. Furthermore, in AbAI mice, the accumulation of type A stealth nanoparticles in inflamed joints was shown to parallel the severity of inflammation. The observed strong therapeutic benefit obtained with the type A stealth nanosteroid in experimental arthritis may have been due to prolonged blood circulation and targeting to the inflamed joint in addition to its sustained release in situ.